Contributing Authors

Dr Amitkumar Chougule
MBBS: Topiwala National Medical College, Mumbai
DPM: KMC, Manipal
MD: CMC, Vellore
Ex Registrar Deaddiction Medicine at the Bombay Drug Deaddiction Centre of Excellence, Mumbai,
under Department of Psychiatry, GSMC and KEM Hospital Mumbai
Current designation: Assistant Professor, Department of Psychiatry, GMC Miraj, Maharashtra
Email: dramitkumarchougule@gmail.com

Dr Reetika Dikshit
MD: LTMMC and Sion Hospital Mumbai
University Gold Medallist, M.U.H.S Nashik
Current designation: Assistant Professor, Department of Psychiatry, LTMMC and Sion Hospital
Mumbai
Email: reetikadikshit@yahoo.com

Dr Lakshmi Shiva
DPM: NIMHANS (Gold Medal)
MD: NIMHANS (Gold Medal)
Current Designation: Senior resident, NIMHANS Bangalore
EMAIL ID: dr.lakshmi0402@gmail.com

Dr Swaleha Mujawar
DPM: Grant Medical college and J.J Group of hospitals, Mumbai
Current Designation: MD Psychiatry resident at D.Y Patil medical College, Pimpri, Pune
Email: Dr.swaleha.mujawar@gmail.com

Dr Akshit Shetty
MD: Kasturba Medical College, Manipal
University Gold medallist
Current designation: Senior resident St John’s hospital Bangalore
Email id: akshithshettyb@gmail.com

Dr Aparajita Shetty
MD: Kasturba Medical College, Manipal
Current designation: Senior resident, St John’s hospital Bangalore
Email id: Aparajita.arora89@gmail.com

2
Dr Subbalakshmi kota
DPM: Kasturba Medical college, Manipal
DNB: IMH, Amritsar, Punjab
Current Designation: Consultant Psychiatrist, ANR Hospital, Jalander, Punjab
EMAIL: lakshmi.kota@gmail.com

Dr Abha Thakurdesai
MD: GSMC and KEM Hospital, Mumbai
Current designation: Post doctorate Fellow at NIMHANS Bangalore
Email id: abha209@gmail.com

Dr Udayan Bhaumik
DPM: Kasturba Medical College, Manipal
Current designation: MD Psychiatry resident at the M.S RAMAIAH MEDICAL COLLEGE BANGALORE
Email id: Udayan.bhaumik@gmail.com

Dr Raviteja Innamuri
DPM: CMC, Vellore
MD: CMC, Vellore
Current Designation: Senior resident, Department of Psychiatry, CMC Vellore
Email: drravitejainnamuri@gmail.com

3
 Foreword

Training Initiative for Psychiatry Postgraduates (TIPPS) is an initiative to provide a

platform to connect all psychiatry postgraduate students in the country to form a network of
peer support group. As part of this initiative we are happy to bring out the series of TIPPS
exam notes.

These notes covers many important topics from paper I and paper II. Before the exams
it is difficult to get reading materials for these topics as the sources are quite varied. The
intention of the notes is to collate and provide the readers with information on the topics in a
concise format with references.

The authors have tried to prepare the content from different sources. The notes does
not provide ready-made answers to any questions which may be asked in exams. We
encourage readers to refer to standard textbooks and references and prepare their own
answers.

We thank the authors for their time and effort in preparing this and invite more people
to come forward in future to support this initiative. We hope that these notes addresses a felt
need of the PG residents and wish them the best in their exam preparations.

Dr. Rishikesh V. Behere

Dr. Naren P. Rao
Dr. Girish Babu N

4
 Index

Sociology: Dr Amitkumar Chougule: (Pg 13 onwards)

1. Prejudice
2. Spirituality and Mental Health
3. Social Isolation
4. Creative thinking
5. Attitudes
6. Stress-Diathesis model
7. Emotional intelligence
8. Crowd behaviour
9. Disaster Management

Genetics in Psychiatry: Dr Amitkumar Chougule (Pg 33 onwards)

1. Genetic counselling in Psychiatry
2. Genetics of mood disorders / BPAD/ Role of family studies in understanding aetio-
pathogenesis of mood disorders
3. What is the difference between phenotype and genotype? Discuss modes of genetic
transmission of psychiatric disorders with examples/ Genotype-Phenotype

4. What is pharmacogenetics? describe its research and its implications in treatment of

psychiatric disorders
5. Pharmacogenomics
6. Adoption studies
7. Endophenotypes/ Genetic marker
Biostatistics: Dr Amitkumar Chougule (Pg 63 onwards)
1. Tests of significance/Measures of statistical significance
2. Non-parametric statistics
3. Chi squared test / Chi Square test in medical research/ Application of Chi-square test
in Psychiatric research
4. Relevance of Cohort study in the field of research in behavioural medicine
5. Analysis of Variance (ANOVA). It’s role in research in behavioural medicine/ ANOVA
6. Describe how a case control study is done with an example
7. Applied statistics of Pearson correlation co- efficient

5
 8. Type I and Type II errors / Discuss about Type I and Type II error in biostatistics
9. Randomized controlled Trail
10. Define Double Blind study. Describe its role in medical research
11. Normal distribution and standard deviation/ Bell shaped curve
12. What is sample? how will you select an appropriate sample for an epidemiological
study? / Sampling Procedure
13. What is incidence and prevalence? what are different types of prevalence? discuss
briefly their significance
14. What is the difference between meta -analysis and systematic review? describe two
metanalysis studies / Metanalysis
15. What is qualitative research? essential features, strengths and limitations of qualitative
research? Importance of Quantitative research in Psychiatry
16. Factor analysis
17. Validity of a test
18. Student t test
19. Define reliability of a test instrument in Psychiatry. What are the different types of
reliability and how are they measured? Inter-rater reliability
Functional Neuro- Anatomy: (Pg 129 onwards)
Dr Udayan Bhaumik, Dr Raviteja, Dr Amitkumar Chougule
FRONTAL LOBE
Describe frontal lobe and its functions/ Clinical features and management of Frontal
lobe syndrome

Basal Ganglia
Basal Ganglia / Describe basal ganglia/ Describe the anatomy of Basal ganglia.
Discuss the Neuro Psychiatric conditions associated with Basal Ganglia Dysfunction/
Describe the structure, connections and functions of the ‘Basal Ganglia’ (with
diagrams)
LIMBIC SYSTEM, HYPOTHALAMUS, THALAMUS
1. Describe the structure and functions of the hippocampus/ Discuss the functional
anatomy of hypothalamus, its Dysfunctions in psychiatric disorder
2. Limbic circuit give an account of its lesions / Neuro anatomy of Limbic system with
appropriate diagrams/ Describe the limbic circuit
3. Neuroanatomy of Papez Circuit
4. Caudate Nucleus
5. Thalamus in Psychiatry

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TEMPORAL LOBE:
Temporal lobe and its functions
PARIETAL LOBE:
Functional anatomy of parietal lobe, clinical features and test to assess it
CORPUS CALLOSUM:
Structure, connections and functions of Corpus callosum/ Corpus Callosum
MISCELLANEOUS:
1. Describe the role of reticular activating system in maintenance of consciousness /
Reticular Activating System in the maintenance of consciousness
2. Autonomic nervous system
3. Basic concepts of information processing
4. Arterial supply of the brain / Describe the blood supply to the brain with appropriate
diagrams
5. Cerebral dominance
6. Cerebral laterality
7. Cortical control of eye movements
8. CSF
9. Write an essay on lobar functions
10. Medial Longitudinal Fasciculus
11. Structure and functions of the Pineal gland

Neuro-chemistry: Dr Reetika Dixit, Dr Lakshmi Shiva (Pg 208 onwards)

Monoamine neurotransmitters:
1. Acetylcholine
2. Describe anatomy of monoamine neurotransmitter system
3. Describe the neural pathways, synthesis and metabolism of Dopamine with
appropriate diagrams /Dopaminergic pathways in the brain (with appropriate diagrams)
4. Serotonergic pathways in the brain/ Write in detail about serotonin Neurotransmission
5. Nor-adrenergic pathways in brain

Amino acid Neurotransmitters:

1. Describe the glutamate receptors. Add a note on drugs which act on these receptors /
Glutamate/ Role of CNS glutamate in psychiatry
2. Describe the synthesis, metabolism, pathways and receptors of GABA/ Synthesis of
GABA and GABA receptors

7
Miscellaneous questions:
1. Cannabinoid receptors
2. Cytochrome P450
3. Endogenous opioids. / Opiate receptors / Endorphins/ What are Endogenous opiates
and their relevance to psychiatry?
4. Melatonin
5. Neuro Modulators
6. Neuropeptide Y
7. Neurotrophic factors/ Brain derived neurotrophic factors (BDNF)
8. Neurotrophins
9. Novel Neurotransmitters
10. Prolactin
11. Describe Polymerase chain reaction and its use in psychiatry

Basic Sciences miscellaneous questions: Dr Swaleha Mujawar (Pg 278 onwards)

1. Animal models of dementia
2. Psychophysiological measures of anxiety
3. Tests of Formal thought disorder / Discuss the various approaches to the
assessment of thought disorders in Psychiatry.
4. Discuss the scope and techniques of Behavioural Medicine
5. Clinical assessment of personality. Role of biological, genetic and psychological
factors in the development of personality
6. Discuss doctor-patient relationship and interview techniques with specialised
populations.
7. Mind body dualism
8. Human sexual response cycle
9. Psychology of rape
10. Sensory deprivation
11. Operant conditioning/ Operant Conditioning
12. Fregoli’s syndrome
13. Internet use, abuse and addiction
14. Aggression. predictors of aggression? psychological and social theories of
aggression

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Psychotherapy: Dr Abha Thakurdesai and Dr Amitkumar Chougule (Pg 343
onwards)
1. Behavioural measures used in CBT
2. Discuss basic principles and applications of behaviour therapy / Behaviour therapy for
phobias / Behaviour modification in Panic disorder
3. Types, roles and efficacy of family therapy
4. Procedure and Efficacy of Computerized Cognitive Therapy
5. Psycho-Education In Psychiatric Illness
6. Rational Emotive Behaviour Therapy
7. Client cantered therapy
8. Countertransference
9. Defence mechanisms
10. Existential Therapy
11. Gestalt therapy
12. Interpersonal therapy
13. IPSRT-Interpersonal social rhythm therapy
14. IPSRT-Interpersonal social rhythm therapy

Sleep Medicine: Dr Akshit Shetty and Dr Aparajita Shetty (Pg 388 onwards)

1. Discuss the anatomy, physiology and chemistry of sleep

2. Chronobiology/ Circadian rhythm
3. Describe the physiology in sleep
4. Describe the stages of sleep
5. Discuss the common Parasomnias and sleep related movement disorders
6. Describe the sleep abnormalities seen in Psychiatric and neurologic disorders Sleep
and psychiatry

Psycho-Neuro-Endocrinology: Dr Akshit Shetty and Dr Aparajita Shetty (Pg 413

onwards)
1. Describe in detail about Hypothalamo-Pituitary-Adrenal axis and its relevance in the
causation of various psychiatric disorders
2. Hypothalamic–pituitary–gonadal axis
3. Hypothalamic–pituitary–thyroid axis
4. Psychoneuroendocrinology

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Basic Psychology: Dr Subbulakshmi Kota (Pg 430 onwards)

1. Attachment theory and its implications in Psychiatry

2. Discuss the psychological and biological theories of Hallucinations
3. Psychoanalytical theories of Personality development
4. Self-actualisation and Maslow’s hierarchy of needs
5. Social cognition measurement and its implication in psychiatry
6. Social theories of schizophrenia
7. Social theories of suicide
8. Theories of emotions
9. Theories of Learning and its application in Psychiatry
10. Theories of motivation

Culture and mental illness: Dr Amitkumar Chougule (Pg 473 onwards)

1. Culture and Mental disorders
2. Culture bound syndromes

Neuro-imaging in Psychiatry: Dr Amitkumar Chougule (Pg 484 onwards)

1. Merits of available neuroimaging techniques and their applications in psychiatry

2. Neuroimaging in Psychiatry disorders both in clinical practice and also in biological
surgery research

Intelligence: Dr Amitkumar Chougule (Pg 490 onwards)

1. Define Intelligence and various theories of intelligence/Assessment of intelligence

2. Intelligence (Themes and variations)

Contribution by famous personalities: Dr Amitkumar Chougule (Pg 501 onwards)

1. Jean Piaget: Cognitive theory of development

2. Sigmund Freud: Psycho-sexual stages of development

Miscellaneous: Dr Amitkumar Chougule (Pg 512 onwards)

1. Stress diathesis model

2. Structured clinical assessment

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11
Sociology

Creative thinking

Dr Amitkumar Chougule

12
Introduction:

1. Creative thinking is one of the many thought processes, which humans possess in a
cognitive state.
2. Creative thinking, also known as divergent thinking, is the ability to find unorthodox or
imaginative solutions to regular or even sometimes irregular problems or situations
that one would run into in everyday life.
3. The creative ability to find an abstract solution in a plethora of ordinary scenarios not
only allows for a means of survival, but also to excel, to “think outside the box”.
4. In today’s society, success is mostly found when one differentiates themselves from
others in a creative way.
Divergent vs Convergent Thinking:

• Divergent thinking plays off of convergent thinking, which is a thought process that
follows a structured path to reach an answer. With this process, the solution found is
the, “correct” one (Callaghan & Growney, 2013). It may be the most basic, however, it
is not guaranteed to be the easiest or most efficient.
• Creative thinking enables the cognitive ability to “work smart and not hard”. The
foundation of economics is to allocate a limited number of resources, due to scarcity.
In a world ruled by the economy, it is more beneficial to think creatively and to be
efficient, to be “ahead of the curve” than to be average or ordinary.

Sources of Creative Ideation

Biological:

• The ability to think divergently seems to be related to “the survival of the fittest”
concepts, but more like “the survival of the smartest”.
• The most intelligent people are most likely to advance in today’s society, simply
because they are intelligent. However, even if a subject was considered to have an
average intelligence, they could choose to think divergently and still be successful.
• Divergent thinking is in human DNA, and structured through evolution; the ability to
think creatively is pronounced with “oxytocin, a hypothalamic neuropeptide” (De Dreu
et al., 2014).
• From the tests conducted by De Dreu et al. (2014), it was shown that oxytocin is found
in both humans and animals and improves “approach orientation”, allowing the
subjects to think more creatively and less “analytically”.
• Approach orientation, or goal orientation theory concerns individuals who are positively
incentivized to achieve.
• Approach orientation has been linked to “creative ideation” and an “increase in
capacity” of divergent thinking for problem solving, opposed to convergent thinking (De
Dreu et al., 2014).

Forgetting:

1. Sometimes knowledge of old ideas or concepts can sometimes “impede” the creative
process and keep new ideas from forming (Storm & Patel, 2014).

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 2. Storm & Patel (2014), describe this as “Mental Fixation”, this can happen while
“remembering, solving problems, or generating creative ideas”.
3. Forgetting plays an important part in overcoming fixation and therefore and lead to new
ideas or divergent thinking (storm & Patel, 2014).
4. Storm & Patel (2014), said, “Thus, to understand creativity we must attempt to
understand the noncreative processes that support it, and the present findings suggest
that forgetting may be one such process”.
Music & Mood:

• Heightened emotions of both happiness and sadness stimulate original thought or

divergent thinking.
• Mozart Effect which is a controversial theory that says music may enhance
creativeness or spatial reasoning
• Mood inspires people to do what they choose to do in everyday life. It is not surprising
that there is a correlation found between mood and “creative ideation” (De Dreu et al.,
2014). Most musicians write their best works in times of elevated emotions, this is just
one example of how heightened mood sensitivity effects creative ability.
• When a subject’s moods are congruent with the moods in the music being listened to,
is when the person is most productive or creative (Callaghan & Growney, 2013).
Gender and Divergent Thinking

• No any real correlation was found between gender and divergent thinking in the study
carried out in Egypt.
• In the study carried out in the china it was concluded that male superiority exits when
it comes to divergent thinking.
Self-Image and Creative Processing

• People who judge themselves severely and look down upon themselves with a
negative self-image are less likely to express divergent processing, opposed to a
person who is more “self-compassionate” (Zabelina & Robinson, 2010).
Conclusion:

• Creative thinking is a lot more than just thinking “outside the box”. After seeing how
anatomy, other thought process, moods, music, gender, and self-concept along with
geographical location and cultural environment effect how humans think, there is a
much greater perspective to be had on how the human mind operates and functions
against societal norms and inner controversies.
• Further research should be done on where exactly are creative talents come from and
how Oxytocin plays a roll in contributing to further creative openness and less
restrictive analytical boundaries.

References:

14
1. Callaghan, K. T., Growney, C. M. (2013, Winter). The Impact of Music and
Mood on Creative Thinking. Psi Chi Journal of Psychological Research, 18(4),
164-169.

2. De Dreu, C., Baas, M., Roskes, M., Sligte, D., Ebstein, R., Chew, S., Tong, T.,
Jiang, Y., Mayseless, N., Shamay-Tsoory, S. (2014, Aug). Oxytonergic circuitry
sustains and enables creative cognition in humans. Social Cognitive & Affective
Neuroscience, 9(8), 1159-1165.

3. He, W., Wong, W., Li, Y., Xu, H. (2013, Nov). A study of the greater male
variability hypothesis in creative thinking in Mainland China: Male superiority
exists. Personality and Individual Differences, 55(8), 882-886.

4. Sayed, E. M., Mohamed, A. H. H. (2013). Gender Differences in Divergent

Thinking: Use of the Test of Creative Thinking-Drawing Production on an
Egyptian Sample. Creative Research Journal, 25(2), 222-227.

5. Storm, B. C., & Patel T. N. (2014, Nov). Forgetting as a Consequence and

Enabler of Creative Thinking. Journal of Experimental Psychology. Learning,
Memory & Cognition, 40(6), 1594-1609.

6. Zabelina, D. L., Robinson, M. D. (2010, Jul-Sep). Don't Be So Hard on Yourself:

Self-Compassion Facilitates Creative Originality Among Self-Judgmental
Individuals. Creative Research Journal, 22(3), 288-293.

CROWD BEHAVIOR

15
 Dr Amitkumar Chougule

Introduction:

1. Crowd psychology, also known as mob psychology, is a branch of social psychology.

2. Social psychologists have developed several theories for explaining the ways in which
the psychology of a crowd differs from and interacts with that of the individuals within
it.
3. Major theorists in crowd psychology include Gustave Le Bon, Gabriel Tarde, Sigmund
Freud, and Steve Reicher.
4. This field relates to the behaviors and thought processes of both the individual crowd
members and the crowd as an entity.
5. Crowd behavior is heavily influenced by the loss of responsibility of the individual and
the impression of universality of behavior, both of which increase with the size of the
crowd
Historical aspect:

Literature on crowds and crowd behavior appeared as early as 1841, with the publication of
Charles Mackay's book Extraordinary Popular Delusions and the Madness of Crowds.

Types of crowds:

Momboisse (1967) and Berlonghi (1995) focused upon purpose of existence to differentiate
among crowds:

1. Casual
2. Conventional
3. Expressive
4. Aaggressive
Berlonghi classified crowds based on purpose of gathering:

1. Spectator
2. Demonstrator
3. Escaping

Herbert Blumer's classified crowd on the basis of emotional intensity:

1. Casual
2. Conventional
3. Expressive
4. Acting
His system is dynamic in nature. That is, a crowd changes its level of emotional intensity over
time, and therefore, can be classed in any one of the four types.

Crowds can be active (mobs) or passive (audiences).

Active crowds can be further divided into

16
 1. Aggressive
2. Escapist
3. Acquisitive
4. Expressive
Theoretical perspectives of crowd behaviour:

Gustave Le Bon:

Le Bon held that crowds existed in three stages:

1. Submergence: During submergence, the individuals in the crowd lose their sense of
individual self and personal responsibility. This is quite heavily induced by the
anonymity of the crowd.
2. Contagion: Contagion refers to the propensity for individuals in a crowd to
unquestioningly follow the predominant ideas and emotions of the crowd
3. Suggestion
Freudian theory:

1. Sigmund Freud's crowd behavior theory primarily consists of the idea that becoming a
member of a crowd serves to unlock the unconscious mind.
2. This occurs because the super-ego, or moral center of consciousness, is displaced by
the larger crowd, to be replaced by a charismatic crowd leader.
3. In a crowd, the overall shared emotional experience reverts to the least common
denominator (LCD), leading to primitive levels of emotional expression.
4. This organizational structure is that of the "primal horde" – pre-civilized society - and
Freud states that one must rebel against the leader (re-instate the individual morality)
in order to escape from it
Deindividuation theory:

1. Deindividuation theory argues that in typical crowd situations, factors such as

anonymity, group unity, and arousal can weaken personal controls (e.g. guilt, shame,
self-evaluating behavior) by distancing people from their personal identities and
reducing their concern for social evaluation.
2. This lack of restraint increases individual sensitivity to the environment and lessens
rational forethought, which can lead to antisocial behavior.
3. More recent theories have stated that deindividuation hinges upon a person being
unable, due to situation, to have strong awareness of their self as an object of attention.
This lack of attention frees the individual from the necessity of normal social behaviour.
Convergence theory

1. Convergence theory holds that crowd behavior is not a product of the crowd, but
rather the crowd is a product of the coming together of like-minded individuals
2. Floyd Allport argued that "An individual in a crowd behaves just as he would
behave alone, only more so
3. Convergence theory holds that crowds form from people of similar dispositions,
whose actions are then reinforced and intensified by the crowd
4. Convergence theory claims that crowd behavior is not irrational; rather, people in
crowds express existing beliefs and values so that the mob reaction is the rational
product of widespread popular feeling

17
Emergent norm theory:

• Emergent norm theory states that crowds have little unity at their outset, but during a
period of milling about, key members suggest appropriate actions, and following
members fall in line, forming the basis for the crowd's norms
Social identity theory:

1. Social identity theory posits that the self is a complex system made up primarily of the
concept of membership or non-membership in various social groups.
2. These groups have various moral and behavioral values and norms, and the
individual's actions depend on which group membership (or non-membership) is most
personally salient at the time of action
3. This influence is evidenced by findings that when the stated purpose and values of a
group changes, the values and motives of its members are shown to also change

References:

1. Manstead, ASK; Hewstone, Miles (1996). Blackwell Encyclopedia of Social

Psychology. Oxford, UK: Blackwell. pp. 152–156. ISBN 978-0-631-20289-9.

2. Greenberg, M.S. (2010). Corsini Encyclopedia of Psychology.

3. Toch, Hans (1988). "Psychology of Crowds Revisited". Contemporary

Psychology. 33 (11): 954.

Disaster Management- Mental Health Perspectives

18
 Dr Amitkumar Chougule

Introduction:

Disaster is a very a broad term, which implies a diverse set of circumstances from an act of
terrorism (manmade disaster) to natural calamitkumaries like earth quake. Disasters are
known to have substantial effect on both physical and mental health of the affected population.

Defining disaster:

In 1992 the World Health Organisation’s (WHO) defined disaster as a severe disruption,
ecological and psychosocial, which greatly exceeds the coping capacity of the affected
community.

In 1995, Federal Emergency Management Agency of US have defined disaster as, ‘Any
natural catastrophe, regardless of cause, any fire, flood, or explosion that causes damage of
sufficient severity and magnitude to warrant assistance supplementing State, local, and
disaster relief organization efforts to alleviate damage, loss, hardship, or suffering.

The Disaster Management Act 2005 of India disaster is defined as a catastrophe, mishap,
calamitkumary or grave occurrence in any area, arising from natural or manmade causes, or
be accident or negligence which results in substantial loss of life or human suffering or damage
to, and destruction of property, or damage to, or degradation of, environment, and is of such
a nature or magnitude as to be beyond the coping capacity of the community of the affected
area.

PRINCIPLE OF DISASTER MENTAL HEALTH:

Disaster mental health services are based on the principles of ‘preventive medicine’. This
principle of ‘prevention’ has necessitated a paradigm shift from relief centered post-disaster
management to a holistic, multi-dimensional integrated community approach. This has ignited
the paradigm shift from curative to preventive aspects of disaster management. This can be
understood on the basis of six ‘R’s such as:

1. Readiness (Preparedness)

2. Response (Immediate action)

3. Relief (Sustained rescue work)

4. Rehabilitation (Long term remedial measures using community resources)

5. Recovery (Returning to normalcy)

6. Resilience (Fostering)

DIFFERENT PHASES OF DISASTER MENTAL HEALTH:

Community’s and individual’s reactions to the disaster usually follow a predictable phase:

1. Heroic phase:

19
 Immediately after the disaster, survivors in the community usually show altruistic
behaviour in the form of rescuing, sheltering, feeding, and supporting the fellow
human beings. Hence this phase is called as heroic phase.

This phase usually lasts from a day to weeks depending upon the severity, duration
of exposure and availability of the relief sources from various agencies.

2. Honeymoon phase:

Once the relief agencies step in, survivors are relocated to safer places like relief
camps. Media attention, free medical aid, free food and shelter, VIP visits to the
camp, administrations’ sympathy, compensation package, rehabilitation promises
provides immense sense of relief and faith in survivors that their community will be
restored in no time and their loss will be accounted through monetary benefits.
Hence this phase is called honeymoon phase, which usually lasts for 2-4 weeks.

3. Disillusionment phase:

At the end of 2-4 weeks, relief materials and resources start weaning. VIPs and
politicians visit stops. Media coverage reduces. Administration, relief agencies and
NGO’s involvement start fading.

This brings the survivors to the ruthless world of post disaster life. The reality of
complex process of rebuilding and rehabilitating appears a distant dream because
of administration hurdles, bureaucratic red tapism, discrimination, injustice and
corruption

This harsh reality of the disillusionment phase provides a fertile soil for breeding
mental morbidity which lasts for 3-36 months before the community restores to
harmony. The role of mental health workers is immense during this phase.

4. Restoration phase

PREVALENCE OF MENTAL HEALTH MORBIDITY IN DISASTER AFFECTED

POPULATION:

Prevalence of mental morbidity in disaster affected population varies from 8.6 to 57.3 percent

Mental health disorders noted during disasters can be classified into acute phase (1-3 months)
and longterm phase (>3 months). Majority of the acute phase reactions and disorders are self-
limiting, whereas longterm phase disorders require assistance from mental health
professionals.

COMMON MENTAL DISORDERS SEEN IN THE DISASTER AFFECTED POPULATION:

Common disorders are: Adjustment disorders, depression, post traumatic stress disorder
(PTSD), anxiety disorders, non-specific somatic symptoms and substance abuse.
Researchers have assigned that the PTSD as the signature diagnosis among post disaster
mental morbidity. Prevalence of PTSD reported in literature varies from 4-60%.

ROLE OF MENTAL HEALTH PROFESSIONALS IN DISASTER SITUATION:

20
I. During pre-disaster period (preparedness)

➢ Public Education Activities – Life skills education, educating about the disaster mental
health
➢ Disaster Response Network – to develop collaboration with various existing agencies
like governmental agencies, NGO’s and community health workers
➢ Disaster response training of trainers in disaster mental health
➢ first aid training (both medical and psychological)
➢ counseling skills
➢ stress management
➢ identifying common mental disorders and referral
➢ life skills training
➢ Psycho education regarding mental health in trauma/disaster for the general
population
➢ Community level support and community resilience training
➢ Strengthening Information, Education and Communication (IEC) activities
II. Immediately after the disaster (heroic and honeymoon phases)

➢ Being part of the multi-disciplinary relief team

➢ Rapid assessment (mental health surveillance)
➢ magnitude of the psychological impact
➢ available mental health resources in the affected community
➢ social, cultural and religious perspective of the community
➢ Providing health care
➢ medical and psychological first aid
➢ the pre-existing mentally ill patients
➢ substance intoxication and withdrawal in survivors
➢ crisis intervention
➢ establishing the referral system
➢ Providing targeted disaster mental health interventions to the needy
➢ Disaster psychiatry outreach teams to provide care
➢ Promoting of resilience and coping
➢ Dealing with the victims and volunteers stress (stress management)
➢ Fostering the mass grieving / mourning
➢ Collaborating with administrative and funding agencies
➢ Mental health education – do’s and do not’s
➢ Educating the administrative personnel, local leaders and public
➢ Utilizing mass media to reach the survivors
➢ Initiating collaboration with the local agencies for capacity building and outside
agencies for support
➢ Planning research
III. During disillusionment phase
➢ Providing care for the mental ill patients
➢ Attending to the referrals
➢ Continuing and expanding the capacity building activities
➢ Training of resourceful community members like private physicians/doctors,
primary health care staff, paramedical staffs, school teachers, anganwadi
➢ workers, alternative complementary medicine personnel’s, religious leaders,
spiritual leaders and faith healers

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 ➢ Community outreach camps
➢ Hand holding of the community health workers
➢ Assessment of the interventions and feedback mechanism
The principal components of psychological first aid (Source for this table is modified and
adapted from World Health Organization 2011
1. Getting in touch with survivors
2. Protection from further threat and distress
3. Protecting survivors from unnecessary exposure to additional traumatic events and
trauma reminders
4. Immediate physical care
5. Helping to locate family members
6. Sharing the experience (but not forced)
7. Normalization or Validation of the emotions
8. Facilitating a sense of being in control
9. Linking survivors with sources of support and resources
10. Identifying those who need further help and referral

Debriefing

➢ It is defined as group discussions that occur within 48-72 h after an event and are often
referred to as ‘psychological de-briefings.
➢ Sessions encourage participants to describe and share both factual and emotional
aspects of their disaster experience
➢ Principle behind this debriefing is that immediate processing gives an individual the
ability to cognitively restructure the perceived disaster event so that it is remembered
in a less traumatic way.

ROLE OF PSYCHOTROPIC MEDICATIONS IN DISASTER MANAGEMENT:

➢ Generally use of psychotropic medications is discouraged in disaster management

because of the popular notions like a) disaster reactions are generally normal people
in abnormal situations and b) majority of the symptoms are self limiting
➢ Prophylactic uses of psychotropic medications in survivors are discouraged
➢ There are no well controlled studies to say that prophylactic use of medicine decreases
psychiatric morbidity
➢ use of prophylactic psychotropic medications may be justified in pre-existing mental
illness to avoid relapse, in acute substance withdrawal to avoid complications, suicidal
attempt and severe depression.

References:

Suresh Bada Math, Maria Christine Nirmala, Sydney Moirangthem, Naveen C. Kumar.
Disaster Management: Mental Health Perspective. Indian Journal of Psychological Medicine
Jul - Sep 2015; Vol 37:Issue 3 261

22
 Emotional intelligence

Dr Amitkumar Chougule

1. Definition:

Emotional intelligence (EI) is the capability of individuals to recognize their own and
other people's Emotions, discern between different feelings and label them appropriately,
use emotional information to guide thinking and behavior, and manage and/or adjust
emotions to adapt to environments or achieve one's goal(s).

2. Introduction:

The term first appeared in a 1964 paper by Michael Beldoch

In 1995 Daniel Goleman popularized the term

Goleman defined EI as the array of skills and characteristics that drive leadership
performance.

3. Models of Emotional Intelligence:

a. Ability model:

➢ Concept given by Salovey and Mayer's

➢ Definition of EI:

1. "The ability to perceive emotion, integrate emotion to facilitate thought,

understand emotions and to regulate emotions to promote personal
growth."

2. "The capacity to reason about emotions, and of emotions, to enhance

thinking. It includes the abilities to accurately perceive emotions, to access
and generate emotions so as to assist thought, to understand emotions and
emotional knowledge, and to reflectively regulate emotions so as to
promote emotional and intellectual growth.

➢ The model claims that EI includes four types of abilities:

1. Perceiving emotions – the ability to detect and decipher emotions in faces,

pictures, voices, and cultural artifacts—including the ability to identify one's own
emotions. Perceiving emotions represents a basic aspect of emotional
intelligence, as it makes all other processing of emotional information possible.

2. Using emotions – the ability to harness emotions to facilitate various cognitive

activities, such as thinking and problem solving.

3. Understanding emotions – the ability to comprehend emotion language and to

appreciate complicated relationships among emotions.

23
 4. Managing emotions – the ability to regulate emotions in both ourselves and in
others.

b. Mixed model

➢ The model introduced by Daniel Goleman focuses on EI as a wide array of

competencies and skills that drive leadership performance.

➢ Goleman's model outlines five main EI constructs:

1. Self-awareness – the ability to know one's emotions, strengths, weaknesses, drives,

values and goals and recognize their impact on others while using gut feelings to guide
decisions.

2. Self-regulation – involves controlling or redirecting one's disruptive emotions and

impulses and adapting to changing circumstances.

3. Social skill – managing relationships to move people in the desired direction

4. Empathy – considering other people's feelings especially when making decisions

5. Motivation – being driven to achieve for the sake of achievement

c. Trait model

➢ Developed by K. V. Petrides.

➢ Trait EI is "a constellation of emotional self-perceptions located at the lower levels of

personality."

➢ In lay terms, trait EI refers to an individual's self-perceptions of their emotional abilities.

➢ This definition of EI encompasses behavioral dispositions and self-perceived abilities

and is measured by self-report, as opposed to the ability based model which refers to
actual abilities, which have proven highly resistant to scientific measurement.

3. Controversies and criticisms:

➢ Studies have shown that people with high EI have greater mental health, job
performance, and leadership skills, although no causal relationships have been shown
and such findings are likely to be attributable to general intelligence and specific
personality traits rather than emotional intelligence as a construct.

➢ For example, Goleman indicated that EI accounted for 67% of the abilities deemed
necessary for superior performance in leaders, and mattered twice as much as
technical expertise or IQ.

➢ Other research finds that the effect of EI on leadership and managerial performance is
non-significant when ability and personality are controlled for, and that general
intelligence correlates very closely with leadership.

➢ Markers of EI and methods of developing it have become more widely coveted in the
past decade. In addition, studies have begun to provide evidence to help characterize
the neural mechanisms of emotional intelligence.

24
 ➢ Criticisms have centered on whether EI is a real intelligence and whether it has
incremental validity over IQ and the Big Five personality traits. Review finds that, in
most studies, poor research methodology has exaggerated the significance of EI.

References:

1. Coleman, Andrew (2008). A Dictionary of Psychology (3 ed.). Oxford University

Press. ISBN 9780199534067.

2. Murphy, Kevin R. A critique of emotional intelligence: what are the problems

and how can they be fixed?. Psychology Press, 2014.

25
 Prejudice

Dr Amitkumar Chougule

I. Definition:

A negative prejudgment of a group and its individual members.

II. Prejudice is different from:

1. Attitude which is a distinct combination of feelings, inclinations to act, and

beliefs

2. Stereotype which reflects ideas that groups of people hold about others
who are different from them

3. Discrimination which is a negative behaviour while Prejudice is a negative

attitude

III. Roots/ sources of Prejudice:

1. Social sources:

➢ Unequal status:

Masters view slaves as lazy, irresponsible, lacking ambition—as having those traits that justify
slavery

➢ The self-fulfilling prophecy:

Negative beliefs predict negative behavior (or problems in life)

If a person thinks we are clever or stupid or whatever, they will treat us that way.

If we are treated as if we are clever or stupid we will act, and even become, that way.

The person has thus had their prophecy about us fulfilled.

This is also known as the Pygmalion Effect.

➢ Stereotype threat:

a self-conforming apprehension that one will be evaluated based on a negative stereotype

➢ Social identity:

Self-concept—our sense of who we are—contains not just personal identity (our sense of
personal attributes and attitudes) but also a social identity

➢ In group bias:

The group definition of who you are—your race, religion, gender, academic major—implies a
definition of who you are not.

The circle that includes “us” (the ingroup) excludes “them” (the outgroup)

Thus, a mere experience of being formed into groups may promote ingroup bias.

26
 ➢ Conformity:

If prejudice is socially accepted, many people will follow the path of least resistance and
conform to fashion

They will act not so much out of a need to hate as out of a need to be liked and accepted.

2. Emotional sources:

1. Frustration and aggression: (The scapegoat Theory)

➢ Pain and frustration (a blocking of a goal) often evoke hostility.

➢ When the cause of our frustration is intimidating or unknown, we often redirect

our hostility (displaced aggression)

➢ Scapegoating is a hostile social - psychological discrediting routine by which

people move blame and responsibility away from themselves and towards a
target person or group.

2. Personality dynamics

Need for status, self-regard and belonging

The authoritarian personality:

➢ People with this type of personality seek conformity, security, stability.

➢ They become anxious and insecure when events or circumstances upset their
previously existing world view.

➢ They are very intolerant of any divergence from what they consider to be the
normal (which is usually conceptualized in terms of their religion, race, history,
nationality, culture, language, etc.)

3. Cognitive sources of Prejudice:

1. Categorization: One way we simplify our environment is to categorize—to

organize the world by clustering objects into groups

2. Distinctiveness:

Distinctive people and vivid or extreme occurrences often draw attention and distort judgment.

We define people by their most distinctive traits and behaviors.

3. Fundamental attribution error:

Essentially, the fundamental attribution error involves placing a heavy emphasis on internal
personality characteristics to explain someone's behavior in a given situation, rather than
thinking about external situational factors

27
 4. Just- world Phenomenon:

➢ The belief that people get what they deserve and deserve what they get

➢ Attributing failures to dispositional causes rather than situational causes, which

are unchangeable and uncontrollable, satisfies our need to believe that the
world is fair and we have control over our life.

➢ We are motivated to see a just world because this reduces our perceived
threats, gives us a sense of security, helps us find meaning in difficult and
unsettling circumstances, and benefits us psychologically.

Unfortunately, the just world hypothesis also results in a tendency for people to blame and
disparage victims of a tragedy or an accident, such as victims of rape and domestic abuse to
reassure themselves of their insusceptibility to such eve

28
 Spirituality and Mental Health

Dr Amitkumar Chougule

INTRODUCTION

➢ All along, the majority position of Psychiatry has been that Psychiatry has nothing to
do with religion and spirituality.
➢ Religious beliefs and practices have long been thought to have a pathological basis,
and psychiatrists over a century have understood them in this light. Religion was
considered as a symptom of mental illness.
➢ Jean Charcot and Sigmund Freud linked religion with neurosis.
➢ DSM3 portrayed religion negatively by suggesting that religious and spiritual
experiences are examples of psychopathology
➢ But recent research reports strongly suggest that to many patients, religion and
spirituality are resources that help them to cope with the stresses in life, including those
of their illness.
➢ Many psychiatrists now believe that religion and spirituality are important in the life of
their patients.
➢ The World Psychiatric Association recently established a section on psychiatry and
religion. Lukoff et al. proposed that the diagnostic entities of religious and psycho-
spiritual problems should be incorporated in DSM4 which has been accepted. DSM4,
V 62.89 includes three categories—normal religious and spiritual experiences;
religious and spiritual problems leading to mental disturbances; and mental
disturbances with a religious and spiritual context.
CONCEPT OF SPIRITUALITY:

➢ Spirituality is a globally acknowledged concept. It involves belief and obedience to an

all powerful force usually called God, who controls the universe and the destiny of man
➢ It involves the ways in which people fulfill what they hold to be the purpose of their
lives, a search for the meaning of life and a sense of connectedness to the universe.
➢ The universality of spirituality extends across creed and culture. At the same time,
spirituality is very much personal and unique to each person. It is a sacred realm of
human experience
➢ Spirituality produces in man qualities such as love, honesty, patience, tolerance,
compassion, a sense of detachment, faith, and hope
SPIRITUALITY AND RELIGION

➢ Religion is institutionized spirituality. Thus, there are several religions having different
sets of beliefs, traditions, and doctrines
➢ They have different types of community-based worship programs. Spirituality is the
common factor in all these religions
➢ It is possible that religions can lose their spirituality when they become institutions of
oppression instead of agents of goodwill, peace and harmony
IMPORTANCE OF SPIRITUAL DIMENSION IN MENTAL HEALTH:

Mental health has two dimensions—absence of mental illness and presence of a well-adjusted
personality that contributes effectively to the life of the community.

29
 ➢ Ability to take responsibility for one’s own actions, flexibility, high frustration tolerance,
acceptance of uncertainty, involvement in activities of social interest, courage to take
risks, serenity to accept the things which we cannot change, courage to change the
things which we can change, the wisdom to know the difference between the above,
acceptance of handicaps, tempered self-control, harmonious relationships to self,
others, including Nature and God, are the essential features of mental health.
➢ Spirituality is an important aspect of mental health.
➢ Though Sigmund Freud looked upon religion as an illusion and neurosis, Carl Jung
considered the psyche as a carrier of truth, powerfully rooted in the unconscious mind.
➢ Religion is important, directly and indirectly, in the etiology, diagnosis,
symptomatology, treatment and prognosis of psychiatric disturbances.
➢ Lack of spirituality can interfere with interpersonal relationships, which can contribute
to the genesis of psychiatric disturbance.
➢ Psychiatric symptoms can have a religious content. For example, the loss of interest
in religious activities is a common symptom of depression.
➢ Too much and distorted religious practices are common in schizophrenia.
➢ It is well recognized that some religious states and experiences are misdiagnosed as
symptoms of psychiatric illness. Visions and possession states are examples.
➢ The spiritual background of the patient will help in the diagnosis of psychiatric
disturbance.
➢ They are important in the treatment of psychiatric disturbance because spiritual
matters can be profitably incorporated in psychotherapy.
➢ Spirituality is important in the prognosis of psychiatric conditions. In the spiritual
perspective, a differentiation must be made between cure and healing.
➢ Cure is the removal of symptoms.
➢ Healing is the healing of the whole person.
➢ Hence in psychotherapy, the patient must be helped to accept the handicap and
transform the handicap to a life of usefulness.
CLINICAL AND RESEARCH FINDINGS RELATED TO SPIRITUALITY AND MENTAL
HEALTH

1. Recent studies show that religious beliefs and practices are supportive to cope with
stresses in life and are beneficial to mental health.
2. Athens, found that parents who were more involved in religious activities were more
likely to have harmonious marital relationships and better parenting skills. That in turn
enhanced children’s competence, self-regulation, psychosocial adjustment and school
performance.
3. Miller et al. made a 10-year follow up study on depressed mothers and their offsprings
and reported that maternal religiosity and mother-child concordance in religiosity were
protective against depression in the offspring. They also reported that low level of
religiosity was associated with substance abuse in the offsprings.
4. J. Scott Tonigan, a research professor of psychiatry at the University of New Mexico,
followed up 226 patients of alcohol dependence and reported that spirituality predicts
behavior such as honesty and responsibility which in turn promoted alcohol
abstinence.
5. study on the factors in the course and outcome of schizophrenia was conducted in the
Department of psychiatry, Christian Medical College, Vellore.. It was a collaborative
study among three centers—Vellore, Madras and Lucknow. A two-year and five-year

30
 follow up showed that those patients who spent more time in religious activities tended
to have a better prognosis.
6. The above reports strongly suggest that religious beliefs and practices of psychiatric
patients should be given importance. The sense of hope and spiritual support that
patients get by discussing religious matters help them to cope better. They also
suggest that the importance of religion and spirituality is not sufficiently recognized by
the psychiatric community.
7. Mental health workers must take it seriously since psychiatry cannot afford to ignore
the importance of spirituality and religion in psychiatry.
ROLE OF PSYCHIATRIST:

1. Important that we incorporate spirituality and religious practices in our treatment

protocol.
2. We must propagate the Bio-psycho-socio-spiritual model in our approach in psychiatry.
3. Psychiatric history should be catered to the patients’ spiritual orientation and religious
practices. The psychiatric history should gather information about patient’s religious
background and experiences in the past and what role religion plays in coping with life
stresses. We should respect and support patients’ religious beliefs if these help them
to cope better or do not adversely affect their mental health.
4. Partnership with the religious workers is an useful area
5. Research:
• Although there is substantial body of literature that describes the connection
between mental health and spirituality, we must develop theoretical models to
understand their relationship in practice.
• There are ample opportunities to do research in this area.
• Phenomena such as meditation, religious conversion, faith, mystical
experiences, near death experiences, and rebirth concepts are all unchartered
territories.
6. Treatment:
• If spirituality is related to mental health and if religious beliefs and experiences are
important in the life of the psychiatric patient, it is only natural that we should
include religious concepts in psychotherapy.
• For example, some Christian, Gita, Buddhist and Quran passages can be profitably
used to help the patient to cope with life situation.
• The spiritual concepts are incorporated in the treatment program of Alcoholic
Anonymous. Seven out of the 12 AA steps relate to spirituality.
• D’Souza describes a new psychotherapeutic method, which is called Spiritually
Augmented Cognitive Behaviour Therapy (SACBT). This is a treatment technique,
incorporating spiritual values to Cognitive behavior therapy, which was developed
and promoted at the University of Sydney.Four key areas are emphasized—
acceptance, hope, achieving meaning and purpose and forgiveness.

Reference:

Abraham Verghese. Spirituality and mental health. Indian J Psychiatry Oct-Dec 2008; 50(4).

31
Genetics in
Psychiatry

32
 Genetic counselling in Psychiatry

Dr Amitkumar Chougule

1. Definition:
Genetic counselling is the process by which patients or relatives at risk of a disorder
that may be hereditary are advised of the consequences of this disorder, the probability
of developing or transmitting it, and of the ways in which this may be prevented or
ameliorated" (Harper, 1993).
2. PURPOSE OF GENETIC COUNSELING FOR PSYCHIATRIC DISORDERS
➢ The main purpose of genetic counselling is to educate those seeking counselling
(the consultands) and to provide relevant information concerning the disorder of
interest.
➢ Many misconceptions concerning human genetics and psychiatric illness remain.
➢ Counselling can alleviate some of the following common but mistaken beliefs:
1. If a disorder is genetic, it inevitably occurs in those who carry the harmful
gene(s):
➢ The influence of genetic factors in psychiatric disorders is highly
variable
➢ More commonly than not, there are important environmental and
genetic interactions in the expression of most psychiatric conditions
2. If a disorder is genetic, it is untreatable:
➢ Although many genetic conditions are currently untreatable, most
psychiatric disorders respond to some form of treatment

3. Genetic counseling is associated with eugenics and genocide:

➢ Contemporary genetic counseling is non-directive, with emphasis on
individual autonomy and decision-making ability
➢ The goal of genetic counseling is to disseminate current scientific
knowledge concerning the disorder at hand and to aid the consultand
in making the best possible decision
➢ The broadest purpose of genetic counseling is to reduce the burden of
human suffering.
Mental health care professionals need to understand the limitations of genetic testing and
that the disclosure of such results could lead to psychological harm to the patient, if
effective interventions and follow-up are not made available.

Individuals seeking information from genetic counselling are usually relatives who want to
know the risk of developing a disorder themselves or the risk to their children. Less
commonly, third parties such as legal representatives or professionals involved in adoption
may seek advice.

33
3. STAGES OF GENETIC COUNSELING
Genetic counseling is a time-consuming process, but it can be extremely valuable in
educating those at risk for specific disorder.

Stage 1. Confirm the diagnosis

➢ This implies obtaining a cross-sectional clinical picture as well as a longitudinal

history based on the lifetime course
➢ Counselling under a mistaken diagnosis is far more dangerous than
counselling without the knowledge of the underlying mode of transmission.
➢ Currently, the DSM-5/ ICD-10 is the standard diagnostic manual in the
diagnosis of psychiatric conditions.
➢ In addition, various structured diagnostic instruments are available for research
purposes.
➢ Certain disorders that appear the same may, in fact, be heterogeneous
➢ The same genetic liability may produce a variable clinical picture (variable
expressivity)
➢ Therefore, we cannot overemphasize the importance of obtaining an accurate
diagnosis before proceeding with counselling

Stage 2 . Obtain family history

➢ The second stage of genetic counseling involves diagramming a complete and

accurate pedigree.
➢ A pedigree should include first-degree relatives (parents and siblings), second-
degree relatives (aunts and uncles) and third-degree relatives (grandparents
and cousins)
➢ The family history may reveal the most information about the probable
diagnosis, if it is still uncertain, and the mode of inheritance
➢ The family history includes such information as parental age, ethnic
background, occurrence of abortions, stillbirths, and other deaths, as well as
the ages, sexes, and health of living siblings and children
➢ Primary attention is given to the occurrence of the disorder of interest in the
first degree relatives
➢ Sensitive information such as nonpaternity (when the husband is not the father)
and pregnancy termination may arise during this time
➢ Confidentiality, even from other family members should be assured
➢ Informants may not be familiar with certain diagnostic jargon, therefore using
layman's language to explore conditions of interest may be necessary
➢ Structured diagnostic instruments for establishing psychiatric diagnoses in
relatives are also available e.g., the Family Interview for Genetic Studies [FIGS]
➢ Attempts to obtain medical and/or psychiatric records on affected family
members can be time consuming but may be very important prior to proceeding
with genetic counselling
➢ Collecting family information may take time and may also involve speaking to
other relatives who are more knowledgeable about affected individuals in the
family.

34
Stage 3. Assess the recurrence risk

➢ The inheritance pattern of a disorder is often established by careful examination

of the pedigree.
➢ However, the patient may appear to be an isolated case.
➢ For most families with psychiatric conditions, in the absence of a clear mode of
genetic transmission, the counselor should refer to empirical risk estimates for
specific disorders.
➢ For example, siblings of a patient with schizophrenia have an 8.2% risk of
developing schizophrenia if neither parent is schizophrenic, which is 8 times
higher than the risk for the general population; but the risk is increased to 13.8%
if one parent is schizophrenic.
Stage 4. Evaluation of the consultand

➢ Before conveying genetic risks and burdens to the consultand, the mental
health professional must assess the intellectual and emotional capacity of the
individual
➢ Does the consultand seek information only, or does s/he also seek advice?
➢ Do they want advice for themselves or for their relatives?
➢ Humane genetic counseling must be directed at the appropriate level of the
consultand.
Stage 5. Evaluating Burdens and Benefits

➢ Helping a consultand make a reproductive choice goes beyond simply telling

them the probability that a potential child will have a specific disease
➢ The consultant also must help the consultand balance the potential burdens of
the child being ill with the potential benefits of having the child
➢ The benefits of having children will be unique to each consultand; they will vary
with culture, values, religion and the personality of the consultand
➢ Thus, one cannot dictate what these benefits will be.
➢ Instead, the counselor should (in a nondirective manner elicit) from the
consultand a discussion of these perceived benefits.
Stage 6. Forming a plan of action.

➢ Once the benefit/burden ratio is understood, the clinician is responsible for

assisting the consultand in forming a reasonable plan of action for deciding
among his/her options
➢ Since specific genes for most psychiatric disorders are still unknown,
presymptomatic and prenatal testing are currently not options
➢ However, once molecular genetics studies enable identification of the affected
genetic region for a specific disorder, genetic testing may then be an option in
risk assessments
➢ As we will discuss in a later section, there are many human genetic diseases
where presymptomatic and prenatal testing are currently available
➢ Specific genetic tests are likely to be available for psychiatric disorders in the
near future
➢ Major life decisions cannot be made by the clinician (i.e., couples seeking
advice on family planning)

35
 ➢ S/he must help the potential parents predict possible consequences to the
psychiatric condition (if inherited), but not pressure or rush the prospective
parents to make a decision
➢ S/he must educate the consultands in regard to other current reproductive
options, such as impregnation by artificial donors (egg or sperm) or adoption
➢ The responsibility of the counselor is to help consultands make informed
decisions most consistent with their cultural, religious, and ethnic background.
Stage 7. Follow-up

➢ The final stage of genetic counseling must be follow-up

➢ Typically this involves writing a follow-up letter that summarizes the discussion
➢ This letter serves as a written summary for the consultand and it provides
him/her information to share with interested relatives
➢ A follow-up appointment allows continued assessment of consultand's
understanding of the previous discussions
➢ In addition, it gives the clinician the opportunity to obtain more information, such
as subsequent births or other family members becoming affected
➢ If the mode of inheritance becomes apparent with the additional information,
then recurrence risks can be revised for greater accuracy
References:

1. Jane Scourfield, Peter McGuffin. Familial risks and genetic counselling for common
psychiatric disorders. Advances in Psychiatric Treatment (1999), vol. 5, pp. 39-45.
2. Sian Jenkins, Michael Arribas-Ayllon. Genetic Counselling for Psychiatric Disorders:
Accounts of Psychiatric Health Professionals in the United Kingdom. J Genet Counsel
(2016) 25:1243–1255.

36
 Genetics of Mood disorder

Dr Amitkumar Chougule

Genetics of mood disorders /Role of family studies in understanding aetio-pathogenesis of

mood disorders
INTRODUCTION
1. The substantial role of genes in the susceptibility to mood disorders has long been
supported by family, twin and adoption studies
2. However, genes clearly only contribute a predisposition that must interact with
environmental factors in order to cause the disease
3. Studies of the inheritance of different forms of mood disorder and other psychiatric
disorders suggest complex genetic relationships.
GENETIC EPIDEMIOLOGY
Genetic epidemiological studies can provide a great deal of information about the familial and
genetic nature of a disorder by examining the rates of illness among relatives.
1. Family studies:
➢ Family studies address the question of whether a disorder is familial and compare
the rates of illness among first-degree relatives of a proband with the disorder to
either the rates in the general population or the rates in first-degree relatives of
control subjects.
➢ Compared to a rate of 1 percent in the general population, family studies indicate
a sevenfold higher morbid risk to first-degree relatives of bipolar probands,
suggesting a strong familial risk.
➢ Similarly, family studies of probands with major depression reveal morbid risks for
depression among first-degree relatives that are elevated two- to threefold over the
general population.
➢ Major depression is generally found at an elevated rate in the families of bipolar
probands, although the rate of bipolar disorder is only slightly elevated in the
families of probands with major depression.
Disadvantages:
➢ Family studies clearly indicate that mood disorders are familial but are unable to
distinguish whether it is genetic or environmental factors that mediate the familial
transmission.
➢ Families might share a variety of different environmental factors that could transmit
the illness, including shared exposure to infectious agents, toxins, and other brain
insults.

2. Twin studies:
➢ Twin studies provide the most powerful approach to separating genetic from
environmental factors, or “nature” from “nurture”
➢ The most common strategy is one in which both monozygotic (MZ) and same-sex
dizygotic (DZ) twin pairs are identified with one twin having a mood disorder
➢ The cotwins are then examined to determine the proportion of twin pairs in which
both twins are affected. This is termed the concordance rate

37
 ➢ As the twin pairs have been raised together and share the same environmental
factors, a difference in concordance rate between MZ and DZ pairs reflects the role
of heritable genetic factors.
➢ Twin studies generally find a two to fourfold increase in concordance rate for mood
disorder in MZ twins compared to DZ twins, providing the most compelling data for
the role of genetic factors in mood disorders
➢ It is equally noteworthy that the concordance rate for MZ twins is only around 70
to 80 percent, not 100 percent. This is clear evidence that nonheritable
environmental factors also play a significant role in mood disorders.
➢ The MZ to DZ concordance ratio for bipolar–bipolar pairs is higher than that for
depression–depression pairs, indicating a greater role for genetics in bipolar
disorder than in depression.
LIMITATIONS:
➢ The argument that parents treat MZ twins and DZ twins differently, so environment
is not equally shared.
3. Adoption studies:
➢ Adoption studies provide an alternative approach to separating genetic and
environmental factors in familial transmission
➢ The most common experimental design is one in which probands are identified
who have a mood disorder and were adopted at birth
➢ The rates of psychiatric illness are then determined in both the biological and
adoptive parents
➢ Although only a limited number of such studies have been reported due to the
difficulty in obtaining subjects, these results of such studies are supportive of the
role of genetics and are generally consistent with the twin data
4. Large population-based Studies:
➢ Swedish national registry: suggested that the heritability of bipolar disorder was 59
percent
➢ Danish sample: study revealed heritability estimates of 62% for Bipolar disorder
and 32 percent for major depression
In summary, family and twin data collectively suggest that genes explain approximately 75
percent of the etiology of bipolar disorder and 37 percent of major depression.

GENETIC FEATURES OF MOOD DISORDERS:

For mood disorders, there is no 1-to-1 relationship between the genes (genotype) and the
expressed trait (phenotype) that is transmitted in a simple and predictable fashion as observed
for Mendelian traits. Therefore, mood disorders are said to be complex genetic disorders.

Factors associated with complex genetics of mood disorders:

1. Penetrance
2. Variable expressivity
3. Genetic heterogeneity
1.Penetrance in mood disorders:
• The probability that someone will manifest a trait given that they have a certain
genotype is termed the penetrance of the gene.
• Mood disorders are said to have reduced penetrance (less than 100 percent)

38
 • The penetrance of mood disorder genes increases with age, from a low risk for
illness in childhood to a maximum in adulthood.
• Non-penetrant carriers:
o Individuals who have the genes for mood disorder but do not develop
the disease
• Phenocopies
o Individuals who have mood disorder but do not have the genes. Such
individuals with purely environmentally caused disease.
2. Variable expressivity refers to the phenomenon of the same gene or group of genes
resulting in a variety of different forms of illness
3. Heterogeneity refers to the likely role of multiple genes in the aetiology of illness.
MODELS OF TRANSMISSION OF MOOD DISORDERS:
1. Heterogeneity model:
➢ Involves multiple single major loci
➢ Multiple genes for mood disorder exist in the population, each able to alone
cause mood disorder
➢ Possibility of a large number of rare alleles, each of strong effect
➢ In individual and their family, the illness would result primarily from one gene,
but that variant would be quite rare
2. Additive model: (Polygenic quantitative trait model)
➢ Many genes may add together to produce a cumulative predisposition to illness
➢ Alleles for mood disorder would primarily reside in individuals without mood
disorder as they have too few polygenes to develop the illness
3. Gene interactions model:
The probability of one gene manifesting the phenotype is modulated by the interacting effect
of another gene
IDENTIFYING GENES FOR MOOD DISORDERS
Strategies for Gene Identification:
1. Candidate gene approach:
➢ A specific gene is chosen based on its known role in systems relevant to
disease
➢ DNA markers are then genotyped and tested for genetic association
➢ Advantages
o Simpler and more focused
➢ Disadvantages:
o Not systematic or genome-wide
o Requires a hypothesis
o Less likely to result in novel discoveries
➢ The serotonin transporter (SLC6A4) is a relatively weak association with major
depression and bipolar disorder.
➢ BDNF has been associated with bipolar and unipolar mood disorders. A
Val/Met substitution has been identified in the gene that affects processing of
the peptide.
➢ DRD4, SLC6A3 (DAT1), DAOA, NRG1, and DISC1 are associated with mood
disorders

39
Genome-wide studies:
Genetic linkage Studies:
➢ Several hundred or several thousand markers that cover the genome are examined in
families segregating the disease
➢ Markers that are consistently inherited along with disease indicate chromosomal
regions that may harbor disease genes
➢ Linkage studies lead to finding of reproducible chromosomal regions and only a few
specific genes
➢ Not a very powerful for complex or polygenic disorders, such as mood disorders
➢ Across studies, linkage has been demonstrated for 4p, 6q, 8q, 16p, 18p, 18q, 21q, and
Xq
➢ The 22q region was first implicated in psychiatric illness by the observation of psychotic
and mood symptoms in adolescents with a 22q11 deletion syndrome called
velocardiofacial syndrome.
➢ 13q and 22q as the two regions with strongest evidence for linkage and as those most
clearly replicated
➢ While fewer linkage studies have examined major depression, several chromosomal
regions, including 2q, 3q, 12q, 15q, and 18q, have been reported for a recurrent, early-
onset form of illness that appears to be more heritable
GWAS: (Genome wide association study)
➢ In genetic association, the frequencies of the alleles for a marker are compared
between cases with the illness and controls
➢ If an allele is more common in cases than controls, then it may be involved in the illness
➢ Association may be detected if the DNA variant used as a marker is the actual
functional mutation itself or if it is simply very close to the actual mutation
➢ The most common kind of DNA variant is a single nucleotide polymorphism (SNP),
which consists of a single base substitution in the DNA sequence
➢ The second phase of the Human Genome Project, called the HapMap Project has
identified millions of SNPs and has determined their frequency in different populations
➢ In 2007 the Psychiatric Genomics Consortium (PGC) was formed to combine GWAS
datasets across the major psychiatric disorders in the hopes of identifying robust
associations to genes and pathways underlying risk.
➢ The Bipolar Working group of the PGC was able to confirm association to CACNA1C
and ANK3 and identify a novel association to teneurin transmembrane protein 4
(TENM4).
Molecular Pathways
A large number of molecular pathways are associated with mood disorders. They are:
1. CRF signalling
2. Beta-adrenergic signalling
3. Phospholipase signalling
4. Glutamate signalling
5. Histone methylation

Reference:
John R. Kelsoe, M.D., and Tiffany A. Greenwood, Ph.D. Mood Disorders: Genetics. In
Benjamin James Sadock, Virginia Alcott Sadock, Pedro Ruiz, Editor. Comprehensive textbook
of Psychiatry. 10th ed. Wolters Kluwer;2017. P. 4154-64

40
 What is the difference between phenotype and genotype?
Discuss modes of genetic transmission of psychiatric
disorders with examples

Dr Amitkumar Chougule

1. Genotype vs Phenotype:

➢ Genotype: Genetic makeup of an organism with reference to a single trait, set

of traits or an entire complex of traits
➢ Phenotype: Observable constitution of the organism (resulting from the
interaction of the genotype and the environment)

2. Study Designs for Genetic Research

➢ Traditional methods: Family study, Twin study, Adoption study

➢ Newer approaches: Linkage study, Association study etc.

3. Different modes of Genetic transmission:

1.Family study
➢ It provides the first evidence that genes are involved in priming an illness
➢ It can identify which clinical entities are transmitted together in comparison to
random transmission pattern
➢ These studies are conducted with the hypothesis that illness should occur in
the families of affected members at a higher rate than in appropriate control
population
➢ If this hypothesis is accepted, it favors familial aggregation which might be due
to two possibilities, that is, shared diseased genes and shared environment
which is subsequently analyzed
2. Twin study:
➢ Resemblance among relatives may be due to shared genes (nature) or shared
environment (nurture)
➢ Twin study attempts to separate effect of gene from that of the environment
➢ Twin studies are done with certain assumptions:
o Mono zygotic (MZ) twins share 100% of genome
o dizygotic (DZ) twins share approximately 50% of genome
o both MZ and DZ twins share the same environment, thus environment
as a confounding variable can be controlled.
➢ These studies proceed with the hypothesis that if genetic factors are important
in causing a disease, the monozygote concordance rate would be significantly
higher than the dizygotic twins
➢ If MZ concordance is <100%, this would rule out genes as a sole factor causing
a disease

3. Adoption study:
➢ This kind of study attempts to clarify the role of genetic versus environmental
factors in a disease by studying two kinds of informative relationship;

41
 individuals who are genetically related but do not share familial environmental
factors and individuals who share familial environment factors but are not
genetically related
➢ The ability to draw an inference from adoption study is strongest when the
adopted children are separated from their biological parents at birth
➢ The study is conducted as:
1. Parent‑as proband: Compares the rate of illness in the adopted offspring of
ill and well persons. Support for a genetic component is obtained when the
rates of illness is higher in the former. An important example could be the
famous Danish adoption study
2. Adoptee‑as‑proband: Compares the risk between biological relatives of ill
probands with the adoptive relatives
3. Cross‑fostering approach: Compares rates of illness in two types of
adoptee: Individuals with ill biological parents but fostered by healthy
adoptive parents and individuals with healthy biological parents but fostered
by ill adoptive parents
➢ These approaches are only feasible in those countries where adoption register
is strictly maintained
4. Molecular Genetics

➢ Genetic information is coded along the length of a polymeric molecule

composed of only four types of monomeric units
➢ This polymeric molecule, DNA, is the chemical basis of heredity and is
organized into genes, the fundamental units of genetic information
➢ The basic information pathway has been the synthesis of RNA directed by
DNA, which in turn directs protein synthesis
➢ Genes do not function autonomously; their replication and function are
controlled by various gene products, often in collaboration with components of
various signal transduction pathways

Genetic variation‑normal and pathological

➢ A position on a chromosome is termed a locus, a general term, which can refer
to a gene or a segment of DNA with no known function
➢ DNA sequences that differ at the same locus are termed allelic variants
➢ Since we have two copies of each chromosome, by definition we have two
alleles at each locus. If these alleles are identical the individual is said to be a
homozygote at that locus; if they are different, the individual is a heterozygote
➢ The number of alleles at any locus varies remarkably; at the most polymorphic
loci, hundreds of alleles may be found
➢ Polymorphism in the human genome is important in a practical sense because
it permits gene mapping and hence disease gene identification
➢ There is a normal variation of DNA sequence just as is true of more obvious
aspects of human structure.
➢ Variations of DNA sequence, polymorphisms, occur approximately once in
every 500 nucleotides, or about 107 times per genome
➢ There are deletions and insertions of DNA as well as single‑base substitutions
➢ In healthy people, these alterations obviously occur in noncoding regions of
DNA or at sites that cause no change in function of the encoded protein

42
 ➢ This heritable polymorphism of DNA structure can be associated with certain
diseases and can be used to search for the specific gene involved

Deletions, insertions and rearrangements of DNA:

➢ Studies of bacteria, viruses, yeasts, and fruit flies show that pieces of DNA can
move from one place to another within a genome
➢ The deletion of a critical piece of DNA, the rearrangement of DNA within a
gene, or the insertion of a piece of DNA within a coding or regulatory region
can all cause changes in gene expression resulting in disease
Mutation:
➢ A mutation can be defined as any change in the primary nucleotide sequence
of DNA regardless of its functional consequences
➢ Some mutations may be lethal, others are less deleterious, and some may
confer an evolutionary advantage
➢ Mutations can occur in the germline (sperm or oocytes); these can be
transmitted to progeny
➢ Alternatively, mutations can occur during embryogenesis or in somatic tissues
➢ If the DNA sequence change occurs in a coding region and alters an amino
acid, it is called a missense mutation
➢ Depending on the functional consequences of such a missense mutation,
amino acid substitutions in different regions of the protein can lead to distinct
phenotypes
➢ Small nucleotide deletions or insertions cause a shift of the codon reading
frame (frameshift)
➢ Most commonly, reading frame alterations result in an abnormal protein
segment of variable length before termination of translation occurs at a stop
codon (nonsense mutation)
➢ Mutations in intronic sequences or in exon junctions may destroy or create
splice donor or splice acceptor sites
➢ Mutations may also be found in the regulatory sequences of genes, resulting in
reduced gene transcription
➢ Alternatively, mutation in a single allele can result in haploinsufficiency, a
situation in which one normal allele is not sufficient to maintain a normal
phenotype
Gene mapping:
➢ Techniques involving cloned DNA are used to locate genes to specific regions
of chromosomes, to identify the genes responsible for diseases, to study how
faulty gene regulation causes a particular disease, to diagnose genetic
diseases and increasingly to treat genetic diseases
➢ The isolation of a specific gene from an entire genome requires a technique
that will discriminate one part in a million
➢ Gene localizing thus can define a map of the human genome and there are two
techniques used to accomplish gene localization, that is, somatic cell
hybridization and in situ hybridization.
➢ In in situ hybridization, the simpler and more direct procedure, a radioactive
probe is added to a metaphase spread of chromosomes on a glass slide

43
 ➢ The exact area of hybridization is localized by layering photographic emulsion
over the slide and after exposure, lining up the grains with some histologic
identification of the chromosome

Linkage study
➢ There are two distinct but related paradigms for identifying genes or regions
that confer disease risk:
1. Linkage analysis
2. Association analysis
➢ The traditional approach for locating a disease gene in humans is linkage
analysis, which tests the association between DNA polymorphic markers and
affected status within families
➢ After linkage is detected with an initial marker, many other markers nearby may
also be examined
➢ Markers showing the strongest correlation with disease in families are assumed
to be closest to the disease locus
➢ Linkage analysis uses DNA sequences with high variability (i.e.,
polymorphisms) in order to increase the power to identify markers that are
associated with a disease within families
➢ Historically, different methodological approaches have been applied
➢ Earlier linkage studies employed restriction fragment length polymorphisms,
whereas subsequent studies examined short tandem repeat markers, or
“microsatellites” DNA sequences that show considerable variability among
people, but that have no functional consequences.
➢ More recently, linkage and association studies have examined single
nucleotide polymorphisms (SNPs) to track diseases in families.
➢ Markers in the candidate region identified by linkage analysis can be used to
narrow the location of the disease gene through linkage disequilibrium analysis.
➢ Linkage disequilibrium is a population association between two alleles at
different loci; it occurs when the same founder mutation exists in a large
proportion of affected subjects in the population studied
➢ Usually, the closer the marker is to the disease locus, the greater proportion of
affected subjects who carry the identical allele at the marker
➢ However, in measuring the strength of linkage disequilibrium for a given
marker, it is also important to select unaffected control subjects from the same
population, since an allele shared among affected subjects may also be
common in the general population and thus shared by chance rather than due
to proximity to the disease locus
➢ For complex human diseases, a simple mode of genetic inheritance is not
apparent, and indeed, multiple contributing genetic loci are likely to be involved
➢ Study designs that do not depend on the particular mode of inheritance are
required for linkage analysis
➢ Since affected relatives provide most of information for such analyses, studies
that focus on searching for increased sharing of marker alleles above chance
expectation among affected relatives may be employed
➢ The simplest of such studies involves affected sibships, where allele sharing in
excess of 50% (the expectation when there is no linkage) is sought

44
 ➢ Genetic markers used in linkage analysis are typically duplications or SNPs.
Traditionally, a set of approximately 400 duplication polymorphisms
(microsatellites) were used
➢ These polymorphisms are highly informative, because there can be 10-20
different alleles at one locus, but these had lower resolution that limited them.
➢ More recently, SNPs have been used for linkage analyses; a standard set of
approximately 6000 SNPs for linkage analyses are available, although any
subset of independent SNPs from a genome wide SNP panel could be used
➢ Although individual SNPs are less informative (only two alleles per locus)
increased density of SNP panels allows greater resolution than previous
microsatellite panels.

Association study:
➢ Genetic linkage studies have been successful in mapping genes involved in
Mendelian disorders that have high relative risks in families
➢ These studies, however, have been less successful in mapping complex
disorders
➢ Genetic association studies, which are more similar to traditional epidemiologic
studies that test for an association between an exposure and an outcome, offer
an alternative to linkage studies, although the two are conceptually related
➢ Association studies are commonly used in cases of psychiatric disorders due
to the complexity of the disorder
➢ A typical association study design compares the frequency of marker
genotypes in cases with an appropriate control group
➢ There are two common approaches to association studies, case-control
designs and family‑based designs, which typically investigate trios (mother,
father, and an affected offspring)
➢ In a case‑control study, allele frequencies are compared between a group of
unrelated affected individuals and a matched control sample
➢ This design is generally more powerful than a family‑based design, as large
samples of cases and controls are easier to collect than trios and are less
expensive as they require the genotyping of fewer individuals
➢ Case‑control samples may be the only practical design for traits with a late age
of onset (such as Alzheimer’s disease [AD]) for which parents of affected
individuals are typically unavailable.

➢ The main drawback of the case‑control approach is the potential problem of

population stratification; if the cases and controls are not carefully matched
demographically, then they may display substantial differences in allele
frequency that reflect population differences rather than associations to the
disease
➢ Family‑based association studies are designed to ameliorate the problem of
population stratification. In this design, the nontransmitted chromosomes (the
copy of each chromosome that is not passed from parent to the child) are used
as control chromosomes, and differences between allele frequencies in the
transmitted and nontransmitted chromosomes are examined, eliminating the

45
 problem of stratification, as the comparison group is by definition genetically
similar to the case group
➢ Although more robust to population stratification than a case‑control study,
family‑based studies are only about two‑thirds as powerful using the same
number of affected individuals, as noted previously
➢ Until recently, it was not practical to conduct association studies on a
genome‑wide basis, as relatively few SNPs were available
➢ Therefore, association studies focused on testing one or a few markers in
candidate genes chosen on the basis of their hypothesized function in relation
to a given disease
➢ Recently, however, as a result of international efforts that have identified
millions of SNPs distributed relatively evenly across the genome and that have
developed technology for genotyping them relatively inexpensively,
genome‑wide association (GWA) studies are now a reality
➢ Such studies hold much promise for the identification of common variants
contributing to various common diseases
Epigenetics
➢ The term epigenetics refers to “changes in the genetic material that leads to
phenotypic changes without altering the DNA sequence.”
➢ Epigenetic changes mainly include the methylation of DNA and modifications
of chromatin, such as methylation and acetylation of the histones, the DNA’s
packaging material
➢ Epigenetic changes are acquired during the life of an organism and they are
important for gene regulation, with big differences observed in epigenetic
marks across different tissues
➢ Environmental factors can also influence epigenetic marks through life, before
they are reprogrammed in gametogenesis
➢ Occasionally epigenetic changes can escape reprogramming and be vertically
transmitted across generations and as a result, an acquired epigenetic state
can persist in the next generation
➢ Multiple tools now available enable the assessment of epigenetic variation
across the genome
➢ These tools employ methods using a modification of methylated DNA or
chromatin immuno‑precipitation and microarray hybridization, the latter now
being replaced by modern sequencing methods
➢ It is postulated that epigenetic variation can be causally linked to complex
diseases, including psychiatric disease, and recognizing the interplay between
epigenetics and genetics might help us discover complex disease genes
Reference:
Shreekantiah Umesh, Shamshul Haque Nizamie.Genetics in psychiatry. Indian Journal of
Human Genetics April-June 2014; Volume 20:Issue 2

46
 What is pharmacogenetics? describe its research and its implications in
treatment of psychiatric disorders

Dr Amitkumar Chougule

Introduction and Background:

➢ The term pharmacogenetics was first coined nearly a half century ago when it was
recognized that inherited variation can influence responses to medications.
➢ Earlier studies focused on variation in candidate genes or gene systems believed to
influence the absorption, distribution, or clearance of drugs (i.e., pharmacokinetics) or
mediate their mechanisms of actions via interactions with receptors and/or transporters
and downstream second messengers (i.e., pharmacodynamics)
➢ Pharmacogenomics and pharmacogenetics are used interchangeably
Definition:
Pharmacogenetics:
➢ The study of how genetic variation influences response to drug treatments in terms of
efficacy (i.e., efficacy pharmacogenetics) or tolerability (i.e., safety pharmacogenetics)
➢ The hope is that through pharmacogenetics we will be able to discover genetic profiles
that can be determined by simple genetic tests and that predict how patients will
respond to different psychotropic treatments before they are initiated
➢ Pharmacogenetics will allow physicians to tailor medications to their patients in such a
way that maximizes their efficacy and tolerability, thus ushering in an era of
“personalized medicine”
Two key elements are needed to perform valid pharmacogenomic studies:
1. Explicit and consistent definition of the drug-response phenotype
2. Knowledge of polymorphic candidate genes with relevance to the mechanism of drug
action
The pharmacogenomic process:
➢ The pharmacogenomics process is shown from both a conceptual and procedural
perspective.
➢ The mechanism of action of the drug is determined and the genes that are involved in
the mechanism of action of the drug are identified.
➢ Gene variants are then identified and associated with drug response in clinical trials

47
DRUG MECHANISM
Identify how a drug ‘works’, including binding profile
and drug disposition

TARGET
Identify those gene products implicated in the
mechanism of action of the drug
(e.g. receptor, neurotransmitter, metabolic enzyme)

CANDIDATE GENE
Identify the gene(s) that code for implicated
gene products or those that have been found to be
associated with disease (risk)

GENE VARIANTS
Identify the functional and non-functional variants
of the candidate gene

CLINICAL TRIALS
Perform post hoc study of relationship between
candidate gene variants and drug response
(side-effect profile or efficacy) or drug metabolism

ASSOCIATION ANALYSIS
Analyze relationship between gene variant and selected
trait for statistical significance

CLINICAL TRIALS
Perform studies based on a priori hypotheses with selected patient populations stratified by
genotype;

48
consider design, placebo control, dose, drug

Pharmacogenetics of schizophrenia:
1. The most significant results are the association between drug metabolic
polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic
rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer
(PMs) status may require lower doses of antipsychotic
2. Alternatively, CYP2D6 ultra rapid metabolisers (UMs) will need increased drug dosage
to obtain therapeutic response
3. In particular, there is important evidence suggesting association between dopamine 2
receptor (D2) polymorphisms (Taq I and -141-C Ins/Del) and a dopamine 3 receptor
(D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive
dyskinesia
4. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C
polymorphism (-759-T/C) in antipsychotic-induced weight gain
Pharmacogenetics of Affective disorders:
1. 5-HTTLPR:
➢ Intron 2 associated with better response to fluoxetine or paroxetine
➢ Lack of l allele in intron 2 most promoter region, powerfully predicted non-
response
2. Tryptophan hydroxylase gene polymorphism:
➢ Trend towards worse lithium response among subjects
3. G-protein:
➢ Response to antidepressant treatment after 4 weeks

Reference:
David Pickar and Katya Rubinow. Pharmacogenomics of psychiatric Disorders. TRENDS in
Pharmacological Sciences Vol.22 No.2 February 2001.

49
 PHARMACOGENOMICS

Dr Amitkumar Chougule

Introduction and definition:

➢ Pharmacogenomics is the study of the role of the genome in drug response.

➢ Pharmacogenomics can be defined as the technology that analyzes how the genetic
makeup of an individual affects his/her response to drugs. It deals with the influence
of acquired and inherited genetic variation on drug response in patients by
correlating gene expression or single nucleotide
polymorphisms with pharmacokinetics and pharmacodynamics.

➢ Pharmacogenomics and pharmacogenetics are used interchangeably, and in both

cases refer to the study of how genetic variation influences response to drug
treatments in terms of efficacy (i.e., efficacy pharmacogenetics) or tolerability (i.e.,
safety pharmacogenetics).

➢ Pharmacogenetics focuses on single drug-gene interactions

➢ Pharmacogenomics encompasses a more genome-wide association approach,

incorporating genomics and epigenetic while dealing with the effects of multiple genes
on drug response.

Pharmacogenomics aims to:

1. Develop rational means to optimize drug therapy with respect to the patients' genotype
to ensure maximum efficacy with minimal adverse effects

2. Deviate from what is dubbed as the "one-dose-fits-all" approach

3. Eliminate the trial-and-error method of prescribing, allowing physicians to take into

consideration their patient's genes, the functionality of these genes, and how this may
affect the efficacy of the patient's current or future treatments

4. Provide an explanation for the failure of past treatments

5. Promise the advent of precision medicine and even personalized medicine in which
drugs and drug combinations are optimized for narrow subsets of patients or even for
each individual's unique genetic makeup

6. Achieve better treatment outcomes, greater efficacy, minimization of the occurrence of

drug toxicities and adverse drug reactions (ADRs).

In order to provide pharmacogenomic recommendations for a given drug, two possible types
of input can be used:

1. Genotyping or exome

2. Whole genome sequencing

Sequencing provides many more data points, including detection of mutations that
prematurely terminate the synthesized protein (early stop codon).

50
Pharmacogenetic Studies for Antidepressants:

➢ Multiple pharmacogenetic studies have been carried out on the relationship between
genes coding for CYP450 enzymes, which are involved in the metabolism of many
different xenobiotics, and antidepressant treatment responses.

➢ CYP2D6 and CYP2C19, which together with CYP2C9 metabolize virtually all SSRIs
have received the greatest attention.

➢ CYP2D6 is constitutively expressed in the liver and is responsible for metabolizing

approximately 25% of drugs known to be metabolized by CYP450 enzymes.

➢ It is the key enzyme in the metabolic pathway of many antidepressants.

➢ Because CYP2D6 is not inducible, functional genetic variation and “environmental”

inhibitors of the enzyme are the only factors that can modify its activity, making it a
good candidate for pharmacogenetic testing.

➢ Over 90 genetic variants have been identified in CYP2D6. These variants have been
functionally classified into four phenotypic groups based on their effects on enzyme
activity:

1. Poor metabolizers (pms)

2. Intermediate metabolizers (ims)

3. Extensive metabolizers (ems)

4. Ultrarapid metabolizers (ums)

➢ A commercially available pharmacogenetic test has been clinically approved to test for
the CYP2D6 and CYP2C19 genetic variants based on this characterization.

➢ The largest study from STAR*D included 1,877 genotyped subjects and found no
association between variation in CYP2D6 or CYP2C19 and either efficacy or
tolerability.

➢ 5HT1A and 5HT2A code for serotonin receptors that are the targets of certain
antidepressants and atypical antipsychotics.

➢ Interestingly, an association between 5HT2A and antidepressant efficacy was one of

the leading pharmacogenetic findings from STAR*D.

➢ TPH1 codes for tryptophan hydroxylase which is the rate limiting enzyme in the
biosynthesis of serotonin.

Overview of Pharmacogenetic Studies of mood stabilizers

➢ There is a relative dearth of pharmacogenetic studies of mood stabilizers

➢ Almost all of these examined lithium

Pharmacokinetics of antipsychotics:

➢ Just as they do with antidepressants, the CYP450 enzymes play a leading role in the
pharmacokinetics of antipsychotics

51
 ➢ Along with CYP2D6, CYP1A2, CYP3A4, and CYP3A5 are the key enzymes
responsible for metabolizing most commonly use antipsychotics.

➢ A number of studies have examined the association between variants in the genes
coding for these enzymes and antipsychotic response.

➢ The majority of these have studied adverse effects, and in particular TD

➢ A meta-analysis of studies on TD provided evidence of an increased risk with loss of

function alleles in CYP2D6.

Pharmacodynamics

➢ Dysregulation of the dopaminergic system was among the first pathological findings
observed in schizophrenia, and dopamine inhibition is a common feature of most
antipsychotics, particularly the FGAs.

➢ Evidence suggests that dopamine antagonism may be required for antipsychotic

activity, with PET studies showing that a certain level of blockade of dopaminergic
receptors in the striatrum is needed to sustain a therapeutic effect, while excess
blockade can lead to extrapyramidal side effects.

➢ There are five subtypes of dopamine receptors (D1–D5), and of these D2 and D3 are
the most widely implicated in pharmacogenetic studies of antipsychotics.

➢ Three polymorphisms in DRD2 which encodes the D2 receptor have received the
greatest attention.

➢ These include the Taq1A polymorphism, which is located approximately 10 kb from

the 3’ end of the gene and has no known functional effect

➢ the −141-C Ins/Del polymorphism in the promoter region, which has been associated
with lower expression of the D2 receptor in vitro and higher D2 density in the striatum
in vivo

➢ Ser311Cys, a relatively common coding polymorphism that has been shown to reduce
signal transduction via the receptor

➢ At least fourteen studies have examined the relationship between DRD2

polymorphisms and efficacy of both FGAs and SGAs, while twenty-one studies have
investigated adverse effects, including TD, weight gain and neuro-malignant syndrome

➢ In a recent meta-analysis of four different genes and TD, a significant association was
found with the Taq1A polymorphism in DRD2

➢ The DRD3 gene, which has also been extensively studied, contains a Ser9Gly
polymorphism that has been shown in vitro to influence dopamine binding affinity

➢ Several studies have examined the association between this polymorphism and
efficacy and adverse effects like TD

➢ The serotonergic system has also been implicated in treatment responses to

antipsychotics.

52
 ➢ SGAs in particular display high affinities for serotonin receptors which have been
hypothesized to mediate, at least partially, their therapeutic action.

➢ Several polymorphisms in both 5HT2A and 5HT2C have been investigated in multiple
studies of treatment response and adverse effects

Pharmacogenetics in Clinical Practice

Only one pharmacogenetics test has been approved by the Food & Drug Administration (FDA)
for clinical use in psychiatry. This is the AmpliChip CYP450 Test marketed by Roche Molecular
Systems. It uses Affymetrix microarray-based genotyping technology with more than 15,000
oligonucleotide probes to assay for 20 CYP2D6 alleles, 7 CYP2D6 duplications, and 3
CYP2C19 alleles.

The test includes software with an algorithm to predict CYP2D6 and CYP2C19 phenotypes
(i.e., PM, IM, EM, and UM) based on the identified alleles.

Challenges to Clinical Translation

➢ Despite notable progress in research over the past decade, the promise of
pharmacogenetics in psychiatry has not yet been fully realized

➢ How genetic factors influence treatment response to psychotropic medications is not

clear

➢ The studies carried out to date suggest a number of intriguing hypotheses that merit
further investigation, but they do not point to any definitive associations that can be
used with confidence to predict how a patient will respond to a particular treatment

➢ The difficulty with the pharamcogenetic associations thus far reported is the lack of
consistent findings. For every positive association, there are typically several negative
studies that cast doubt on the finding. As a result, it is difficult to draw firm conclusions
about the clinical relevance of any genes that may be implicated.

There are several reasons for the difficulty:

1. Treatment responses to psychotropic medications are complex phenotypes

2. Psychotropic medications may act on a number of different molecular pathways to

exert their therapeutic effect, and in turn they may be acted on by number of different
molecular pathways in the process of their absorption, distribution and elimination

3. Multiple variants in distinct and converging genetic pathways may independently and
interactively contribute to a particular drug response

4. In addition, multiple environmental factors may further contribute to variability in the

response

5. It is particularly challenging to conduct appropriately designed pharmacogenetic

studies that can illuminate the complex architecture of treatment responses

53
 6. The studies carried out to date have had rather small sample sizes and short periods
of follow-up, largely because it is costly and logistically challenging to ascertain and
prospectively evaluate patients in such studies

References:

1. David Pickar, Katya Rubinow. Pharmacogenomics of psychiatric Disorders. TRENDS

in Pharmacological Sciences February 2001; Vol.22:No.2.

2. Falk W Lohoff. The future of psychiatric pharmacogenomics. Pharmacogenomics

2011; 12(7), 927–929.

54
 Adoption Studies

Dr Amitkumar Chougule

Introduction:

➢ Adoption studies have been the major source of evidence regarding the joint
contribution of genetic and environmental factors to disease etiology
➢ Adoption studies either compare the similarity between an adoptee and his or her
biological versus adoptive relatives, or the similarity between biological relatives of
affected adoptees with those of unaffected, or control, adoptees.
➢ The latter approach is more powerful because the potentially confounding effect of
environmental factors is eliminated
➢ Thus, the study attempts to clarify the role of genetic versus environmental factors in
a disease by studying two kinds of informative relationship; individuals who are
genetically related but do not share familial environmental factors and individuals who
share familial environment factors but are not genetically related
➢ The ability to draw an inference from adoption study is strongest when the adopted
children are separated from their biological parents at birth
➢ Similar to the familial recurrence risk, the genetic contribution in adoption studies is
estimated by comparing the risk of disease to biological versus adoptive relatives
➢ These estimates of risk are often adjusted for the sex, age, ethnicity, and other
potential factors that may confound the links between adoption status and an index
disease
➢ With the recent trends towards selective adoption and the diminishing frequency of
adoptions in the United States, adoption studies will be less feasible in identifying
genetic and environmental sources of disease etiology
➢ However, the increased rate of reconstituted families comprised of both siblings and
half siblings may offer a new opportunity to evaluate the role of genetic factors in the
transmission of complex disorders
➢ Genetic models predict that half siblings should have a 50% reduction in disease risk
compared to that of full siblings
➢ Deviations from this risk provide evidence for either polygenic transmission, gene–
environment interaction, or other complex modes of transmission
The study is conducted as:

1. Parent‑as proband:
Compares the rate of illness in the adopted offspring of ill and well persons. Support
for a genetic component is obtained when the rates of illness is higher in the former.
An important example could be the famous Danish adoption study
2. Adoptee‑as‑proband:
Compares the risk between biological relatives of ill probands with the adoptive
relatives
3. Cross‑fostering approach:
Compares rates of illness in two types of adoptee

55
Individuals with ill biological parents but fostered by healthy adoptive parents and
individuals with healthy biological parents but fostered by ill adoptive parents
These approaches are only feasible in those countries where adoption register is
strictly maintained

References:
Shreekantiah Umesh, Shamshul Haque Nizamie.Genetics in psychiatry. Indian
Journal of Human Genetics April-June 2014;Volume 20:Issue 2

56
 ENDOPHENOTYPES

Dr Amitkumar Chougule

1. Historical aspects:
• Douglas Falconer’s 1965 gave multifactorial threshold model for diabetes and other
common, non-Mendelizing diseases
• This was adapted to a polygenic model of schizophrenia in 1967.
• Classification of psychiatric diseases on the basis of overt phenotypes (syndromic
behaviors) might not be optimal for genetic dissection of these diseases, which
have complex genetic underpinnings.
• Gottesman and Shields (25, 26) described “endophenotypes” as internal
phenotypes discoverable by a “biochemical test or microscopic examination.”
• Gottesman & Shields (1973) adapted the term from a 1966 paper that attributed
the geographical distribution of grasshoppers to the insects ’ ‘endophenotype’
(John & Lewis, 1966), a neologism alluding to a phenotype that was microscopic
and internal, and therefore obscure to casual observation.
2. Introduction:
• Endophenotypes in psychiatry retain the notion of an internal process, but one that
can be objectively measured, ideally in a robust and reliable fashion, a
characteristic often lacking in the diseases with which they are associated.
• Phenotype represents observable characteristics of an organism, which are the
joint product of both genotypic and environmental influences.
3. Definition:
Gottesman’s definition of an endophenotype is that it should be:

1. Heritable
2. Co-segregate with a psychiatric illness
3. Be present even when the disease is not (i.e. State independent)
4. Be found in non-affected family members at a higher rate than in the population
5. The criterion of state independence was modified to take into account the importance
of epigenetic and developmental factors so that the endophenotype can be manifest
only at a certain age and/or after a challenge
Others have added criteria that require endophenotypes to be part of the:

1. Causal process by which disease arises

2. Be involved in a biologically plausible mechanism of pathogenesis
3. Should be continuously quantifiable
4. Should predict disorder probabilistically
5. Should be closer to the site of primary causative agent (whether genetic or
environmental) than to diagnostic categories.
6. Priority should be given to endophenotypes that are based or anchored in
neuroscience.

57
One important reason for the popularity of endophenotypes is that they are believed to improve
the chances of detecting at a molecular level the genetic variants that contribute to disease
susceptibility.

Endophenotypes provide a means for identifying the:

• “downstream” traits or facets of clinical phenotypes

• “upstream” consequences of genes
• could assist in the identification of aberrant genes in the hypothesized polygenic
systems conferring vulnerabilities to disorders.
The methods available for endophenotype analysis have advanced considerably since 1972

our current armamentarium includes neurophysiological, biochemical, endocrinological,

neuroanatomical, cognitive, and neuropsychological (including configured self-report data)
measures.

Advanced tools of neuroimaging:

1. Functional magnetic resonance imaging (fMRI)

2. Morphometric MRI
3. Diffusion tensor imaging
4. Single photon emission computed tomography (SPECT)
5. Positron emission tomography (PET)
Synonymous terms:

1. Intermediate phenotype
2. Biological marker
3. Subclinical trait
4. Vulnerability marker
5. Genetic marker
“Biological marker” to signify differences that do not have genetic underpinnings and
“endophenotype” when certain heritability indicators are fulfilled.

Application of Endophenotypes:

1. Long QT syndrome
2. Idiopathic hemochromatosis (excessive serum iron)
3. Juvenile myoclonic epilepsy (an EEG abnormality)
4. Familial adenomatous polyposis coli
In psychiatry, a number of attempts have been made to develop and determine the feasibility
of candidate endophenotypes. However, few have met all the criteria

58
59
60
Conclusions: Broader Uses for Endophenotypes

1. Endophenotypes may have additional uses in psychiatry, including uses in diagnosis,

classification, and the development of animal models.
2. The current classification schema in psychiatry were derived from observable clinical
grounds to address the need for clinical description and communication.
3. However, they are not based on measures of the underlying genetic or biological
pathophysiology of the disorders.
4. Endophenotype- based analysis would be useful for establishing a biological
underpinning for diagnosis and classification; a net outcome would be improved
understanding of the neurobiology and genetics of psychopathology.

References:
1. Jonathan Flint, Marcus r. Munafo. The endophenotype concept in psychiatric
genetics. Psychological Medicine 2007;37:163–180.
2. Irving I. Gottesman, Todd D. Gould. The Endophenotype Concept in
Psychiatry: Etymology and Strategic Intentions. Am J Psychiatry 2003;
160:636–645

61
BIOSTATISTICS

62
 ANOVA/ Analysis of Variance. It’s role in research in
behavioural medicine

Definition of statistics:

It is the methodology of collecting, analysing, interpreting and drawing conclusions from

information. It provides methods for:

1. Design: planning and carrying out research studies

2. Description: summarising and exploring data

3. Inference: making predictions and generalising about phenomena represented by

the data

Parametric test:

• A parametric test is one that makes assumptions about the parameters (defining
properties) of the population distribution from which one’s data are drawn

• These tests assume that data is normally distributed and rely on group means

• These tests assume more about a given population and when the assumptions are
correct, they produce more accurate and precise estimates

• Examples of Parametric tests are t-tests and ANOVA

Analysis of Variance (ANOVA):

1. It was developed by R.A. Fisher

2. It is a collection of statistical models used to analyze the differences between group

means and their associated procedures

3. In its simplest form, ANOVA provides a statistical test of whether or not the means of
several groups are equal, and therefore generalizes the t-test to more than two groups

4. Doing multiple two-sample t-tests would result in increased chance of committing a

type I error, which is avoided by doing ANOVA

Characteristics of ANOVA:

1. As exploratory data analysis, an ANOVA is an organization of additive data decomposition,

and its sums of squares indicate the variance of each component of the decomposition

2. Comparisons of mean squares, along with F-tests ... allow testing of a nested sequence of
models

3. It is used to develop and confirm an explanation for the observed data

4. It is computationally elegant and relatively robust

5. ANOVA provides industrial strength (multiple sample comparison) statistical analysis

63
6. It has been adapted to the analysis of a variety of experimental designs

Three classes of models:

1. Fixed-effects model assumes that the data come from normal populations which differ in
their means

2. Random-effects models assume that the data describe a hierarchy of different populations
whose differences are constrained by the hierarchy

3. Mixed models describe situations where both fixed and random effects are present

Types of ANOVA:

Depending on the number of treatments and the way they are applied to the subjects in the
experiment:

1. One-way ANOVA:

It is used to test for differences among >=3 independent groups.

2. One-way ANOVA for repeated measures:

It is used when the subjects are dependent groups; this means that the same subjects are
used for each treatment.

3. 2×2 ANOVA:

The most common type of factorial analysis of variance

It is used when the experimenter wants to study the effects of >= 2 treatment variables

Assumptions of ANOVA:

1. Independence of cases - this is the design requirement.

2. Normality - the distributions in each of the groups are normal.

3. Scale of measurement - dependent variable is interval or ratio.

4. Homogenity of variances - variance of data in groups should be the same.

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

64
 Define Double Blind study

Definition and introduction:

1. Blinding is a procedure in which one or more parties in a trial are kept unaware
of which treatment arms participants have been assigned to, i.e. which
treatment was received in order to avoid bias

2. It refers to the concealment of group allocation from one or more individuals

involved in a clinical research study, most commonly a randomized controlled
trial (RCT)

3. Blinding is an important aspect of any trial

4. How a trial was blinded should be accurately recorded in order to allow readers
to interpret the results of a study

5. If blinding is broken during a trial on individual patients, it needs to be

statistically and/or ethically explained at the end

Aim of blinding in a study:

1. Blinding is used to prevent conscious or unconscious bias in the design of a clinical

trial and how it is carried out

2. This is important because bias can affect recruitment and allocation, care, attitudes,
assessments, etc

3. It is used to ensure the objectivity of trial results

Potential sources of bias in the study:

1. Patient being treated

2. Clinical staff administering treatment

3. Doctor assessing treatment

4. Team interpreting trial results

Who can be blinded in a clinical trial?

1. Participants in a trial

2. Clinicians and data collectors

3. Data analysts

Allocation concealment vs Blinding:

➢ Allocation concealment eliminate selection bias during the process of recruitment and
randomization

➢ Blinding reduces performance and ascertainment bias after randomization

65
Types of blinding:

Type Description

Unblinded or open All are aware of the treatment the participant receives
label

Single blind or
Only the participant is unaware of the treatment they receive
single-masked

Double blind or
double-masked The participant and the clinicians / data collectors are unaware of
the treatment the participant receives

Triple blind Participant, clinicians / data collectors and outcome adjudicators /

data analysts are all unaware of the treatment the participant
receives.

Unblinded study:

1. A trial in which no blinding is used and all parties are aware of the treatment groups

Also called open label study

2. Should be used:

➢ For surgical procedures

3. When changes in lifestyle are required

➢ When endpoints are objective and cannot be interpreted in different ways

➢ For case studies with life-threatening situations

➢ In post-marketing surveillance

➢ When ethical considerations do not permit blinding

➢ When no control group can be used

Single blind study:

➢ A trial in which one party, either the investigator or participant, is unaware of which
treatment the participant is taking. Also called single-masked trial.

➢ Provides some control when double blinding is impossible

➢ Used when the experimental medicine and control cannot be manufactured identically

66
Double blind study:

➢ Also called double-masked trial

➢ Best-controlled trial design

➢ Decreased chance of observational bias

➢ Should be used whenever possible

➢ Double-blind describes an especially stringent way of conducting an experiment which

attempts to eliminate subjective, unrecognized biases carried by an experiment's
subjects (usually human) and conductors

➢ In most cases, double-blind experiments are regarded to achieve a higher standard of

scientific rigor than single-blind or non-blind experiments.

➢ In these double-blind experiments, neither the participants nor the researchers know
which participants belong to the control group, nor the test group

➢ Only after all data have been recorded (and, in some cases, analyzed) do the
researchers learn which participants were which

➢ Performing an experiment in double-blind fashion can greatly lessen the power of

preconceived notions or physical cues (e.g., the placebo effect, observer bias,
experimenter's bias) to distort the results (by making researchers or participants
behave differently from in everyday life)

➢ Random assignment of test subjects to the experimental and control groups is a critical
part of any double-blind research design

➢ The key that identifies the subjects and which group they belonged to is kept by a third
party, and is not revealed to the researchers until the study is over.

➢ Double-blind methods can be applied to any experimental situation in which there is a

possibility that the results will be affected by conscious or unconscious bias on the part
of researchers, participants, or both. For example, in animal studies, both the carer of
the animals and the assessor of the results have to be blinded; otherwise the carer
might treat control subjects differently and alter the results.

Triple blind:

➢ A triple blind trial means that patients, clinicians, data collectors, outcome adjudicators
and data analysts are denied access to details of group assignment

➢ This ensures that bias for or against the tested treatment is very unlikely to occur

➢ Medicine may still be labelled as A or B during analysis

➢ The analyst is blinded as to which treatment is which

➢ Helps to avoid bias in the analysis of results

67
References:

▪ Karanicolas, P., Farrokhyar, F., & Bhandari, M. (2010). Blinding: Who, what, when,
why, how? Canadian Journal of Surgery, 53(5), 345–348. Retrieved 21 August, 2015,
from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947122/

▪ Schulz, K.F., Grimes, D.A. (2002) Blinding in randomised trials: hiding who got what.
Lancet, 359, 696-700. Retrieved 21 August, 2015,
fromhttp://apps.who.int/rhl/LANCET_696-700.pdf

68
 Case control study

Definition:

The observational epidemiologic study of persons with the disease (or other outcome variable)
of interest and a suitable control (comparison/ reference) group of persons without the
disease.

Characteristics of Case control study:

1. A case control study involves two populations – cases and controls

2. Both exposure and outcome have occurred before the start of the study

3. The study proceeds backwards from effect to cause

4. It uses a control or comparison group to support or refute an inference

A subset of the target

population, Study
randomly selected Population
from the populations

Selection by inclusion and Study Non

exclusion criteria Participants Participants

Selection of cases and

controls based on the health Cases Controls
outcome or disease status

Assess prior exposure status

Exposed Unexposed
at some specified time point Exposed unexposed
before disease onset

ELEMENTS OF A CASE CONTROL STUDY:

1. Selection of cases

2. Selection of controls

3. Information on exposure

4. Analysis

69
1. Selection of cases:

➢ All people in source population who develop the disease of interest

➢ Clear definition of outcome to be studied

➢ Prevalent vs. incident cases

➢ Prevalent cases may be related more to survival with disease than to

development of disease

2. Sources of cases:

➢ Hospital/clinic based cases

• Easier to find

• May represent severe cases

➢ Population based (cancer registry)

3. Selection of controls:

➢ Represent the distribution of exposure in the source population of cases

➢ Selected from the same source population that gives rise to the cases

➢ Selected independently of their exposure status

4. Sources of controls:

➢ Population based Sampling of the general population

70
 ➢ Health care facility based

• Patients with other diseases

➢ Case‑based

• Friends, Neighbourhood

Analysis:

INTERPRETING ODDS RATIO

1. OR = 1

➢ Odds of exposure among cases and controls are same

➢ Exposure is not associated with disease

2. OR > 1

➢ Odds of exposure among cases are higher than controls

➢ Exposure is positively associated with disease

3. OR < 1

➢ Odds of exposure among cases are lower than controls

71
 ➢ Exposure is negatively associated with disease

Example: Relationship between lung cancer incidence and drinking status

Suppose we were interested in the relationship between lung cancer incidence and heavy
drinking (defined as ≥ 2 drinks per day)

We conducted a retrospective study for past 10 years where drinking status was determined
at the baseline and cancer endpoints

The 2x2 table is constructed relating lung cancer incidence to initial drinking status

OR =1.67, suggesting that heavy drinking is a risk factor for lung cancer

Strengths:

1. Cost effective relative to other analytical studies such as cohort studies

2. Case-control studies are retrospective, and cases are identified at the beginning of the
study; therefore, there is no long follow-up period (as compared to cohort studies)

3. Efficient for the study of diseases with long latency periods

4. It is possible to look at multiple exposures simultaneously

5. Useful as initial studies to establish an association

Weaknesses:

1. Particularly prone to bias, especially selection, recall and observer bias because they
rely on memory and people with a condition will be more motivated to recall risk factors

2. Case-control studies are limited to examining one outcome

3. Unable to estimate incidence rates of diseases (unless study is population based)

4. Poor choice for the study of rare exposures

5. The temporal sequence between exposure and disease may be difficult to establish

6. It can be difficult to find a suitable control group

72
References:

1) Soben Peter. Essentials of Public Health Dentistry. 5th ed. New Delhi: Arya

Publising House; 2013.

2)Park, Park’s Textbook of Preventive &Social Medicine, 22nd Edition, Jabalpur:

Banarsidas Bhanot,2013.

73
 Chi squared test (Chi Square test in medical research/ Application of Chi-
square test in Psychiatric research

Chi Square test:

➢ It is developed by Karl Pearson.

➢ It is a non-parametric test of significance not based on any assumption/ distributions

of any variable.

➢ It is applied to sets of categorical data to evaluate hoe likely it is that any observed
difference between the sets arose by chance. It is based on frequencies and not on
parameters like mean and SD.

➢ It is statistical hypothesis test in which the sampling distribution of the test statistic is a
chi square distribution when null hypothesis is true.

➢ Degrees of freedom (df): it denotes the extent of independence/ freedom enjoyed by a

given set of observed frequencies.

➢ If df > 2 distribution is bell shaped, df = 2 distribution is ‘L’ shaped with maxim

ordinate at zero and df < 2 distribution is ‘L’ shaped with maxim ordinate at the origin.

➢ Uses: there are three important uses of chi square test

1. Test of association

2. Test of goodness of fit of distribution

3. Test of proportions

1. Test of association:

➢ Most important application of the test.

➢ It measures the probability of association between two discrete attributes. For

example, smoking and cancer, treatment and outcome of disease or vaccination
and smoking etc.

➢ There are two possibilities- either they influence or affect each other or they do not.
In other words, they are either independent of each other or they are dependent
on each other.

2. Test of goodness of fit of distribution:

➢ Test helps to find whether the observed frequency distribution fits in a hypothetical/
theoretical or assumed distribution of qualitative data

➢ Assumption of no difference between the observed and hypothetical distribution is

made (null hypothesis)

➢ Frequency assumed to be equal in each case or either case.

3. Test of proportions

74
 ➢ To find significance of difference in two or more than two proportions.

➢ For example: incidence of diabetes in 20 non obese with that 20 obese persons
or number of diabetics and non diabetics in groups weighing 40-50 kg, 50-60
kg and 60-70 kg.

Assumptions for applying chi square test:

1. Random sample

2. Data must be in the form frequencies

3. Frequency data must have a precise numerical value and organised into groups

4. All the in the sample must be independent

5. Lowest expected frequency should not be less than 5

Limitations of chi square test:

1. Can be applied in only on fourfold table

2. Will not give result if the expected value in any cell is less then 5

3. If the sample total is less than 50, need to be interpreted in caution

4. Test only tells about presence or absence of association between two events and not
strength of association

5. Tells only about probability of occurrence and does not indicate cause and effect
relationship

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

75
 Relevance of Cohort study in the field of research in behavioural
medicine

Introduction:

1. A cohort study is a type of epidemiological study in which a group of people with a

common characteristic is followed over time to find how many reach a certain health
outcome of interest (disease, condition, event, death, or a change in health status or
behaviour.

2. In epidemiological terms the cohort is a group of people with something in common,

usually an exposure or involvement in a defined population group.

3. It is a type of analytical study which is undertaken to obtain additional evidence to

refute or support existence of association between suspected cause and diseases

4. Other names of cohort study are Longitudinal study, Incidence study and forward
looking study

Features of cohort studies

1. Cohorts are identified prior to appearance of disease under investigation

2. The study groups are observed over a period of time to determine the frequency of
disease among them

3. The study proceeds from cause to effects

Indications for cohort study:

1. There is good evidence of an association between exposure and disease, from other
studies

2. Exposure is rare

3. Attrition of study population can be minimized

4. Sufficient fund is available

76
 Population

Sample

Not exposed/
Exposed/ Variable Variable absent
present

Condition/ Disease Condition/ Disease Condition/ Disease Condition/ Disease

develops does not develop develops does not develop
(a) (b) (c) (d)

Study design for a cohort study

Consideration during selection of Cohort:

1. The cohort must be free from disease under study

2. Insofar as the knowledge permits, both the groups should be equally susceptible to
disease under study

3. Both the groups must be comparable in respect of all variable which influence the
occurrence of disease

4. Diagnostic and eligibility criteria of the disease must be defined beforehand

Types of cohort study:

Prospective cohort study:

1. The common strategy of cohort studies is to start with a reference population (or a
representative sample thereof), some of whom have certain characteristics or
attributes relevant to the study (exposed group), with others who do not have those
characteristics (unexposed group)

2. Both groups should, at the outset of the study, be free from the condition under
consideration

3. Both groups are then observed over a specified period to find out the risk each group
has of developing the condition(s) of interest

4. Framingham Heart Study Framework Initiated in 1948 to study the relationship of a

variety of factors to the subsequent development of heart disease

5. Problem of prospective study:

• Long duration of study

77
 • Continuous funding for long period

• Attrition of study subjects

Retrospective Cohort Study:

1. A retrospective cohort study is one in which the outcome have all occurred before the
start of the investigation

2. Investigator goes back to the past to select study group from existing records of the
past employment, medical and other records and traces them forward through time
from the past date fixed on the records usually to the present

3. Known with the name of Historical Cohort and noncurrent cohort

Ambi-directional cohort Study:

1. Elements of prospective and retrospective cohort are combined

2. The Cohort is identified from past records and assessed for the outcome

3. The same cohort is the followed up prospectively into future for the further assessment
of outcome

Prognostic cohort studies:

Prognostic cohort studies are a special type of cohort study used to identify factors that might
influence the prognosis after a diagnosis or treatment

Advantages of a cohort study:

1. A cohort study directly measures the risk and of a health outcome occurrence over
time

2. Cohort studies are an efficient means of studying exposures tend to be better for rare
outcomes

3. Cohort studies allow the investigator to assess multiple outcomes of a single exposure

4. Cohort studies establish temporal relationships exposure and outcome

5. Exposure clearly precedes outcome because the population under study at is free of
the outcome of interest

6. Cohort studies avoid recall bias as well survival bias

7. Therefore, cohort studies are the best observational studies to study the cause and
effect relationships

Disadvantages of cohort studies:

1. Cohort studies require large sample sizes, especially when the outcome is rare,
defined as less than 1 event per 1000-person years (e.g., all specific cancers).
Therefore, studies tend to be expensive and time consuming

78
 2. When there are losses to follow-up (individuals leave the cohort before the end of
follow-up) biases occur

3. Thus, individuals who leave the cohort prematurely may have a different baseline risk
than members who remain in the cohort throughout the entire length of follow-up.
Therefore, the study may not be generalizable to the original target population, but
those who remained under investigation the length of the study

4. Also, any differences in quality of measurement of exposure or disease between

exposed and non-exposed cohorts may introduce information bias and thereby distort
the results

References:

1. Dr. Carl M. Shy, Epidemiology 160/600 Introduction to Epidemiology for Public Health
course lectures, 1994-2001, The University of North Carolina at Chapel Hill,
Department of Epidemiology

2. Rothman KJ, Greenland S. Modern Epidemiology. Second Edition. Philadelphia:

Lippincott Williams and Wilkins, 1998.

3. The University of North Carolina at Chapel Hill, Department of Epidemiology Courses:

Epidemiology 710, Fundamentals of Epidemiology course lectures, 2009-2013, and
Epidemiology 718, Epidemiologic Analysis of Binary Data

79
 Factor Analysis

Introduction:

➢ It is a data reduction technique designed to represent a wide range of attributes on a

smaller number of dimensions.

DEFINITION

1. “A statistical approach that can be used to analyse interrelationship among a large

number of variables and a explain these variables in terms of their common underlying
dimension(factor)”

2. Factor analysis is a general name denoting a class of procedures primarily used for
data reduction and summarization

3. Variables are not classified as either dependent or independent. Instead, the whole set
of interdependent relationships among variables is examined in order to define a set
of common dimensions called Factors

Purpose of Factor Analysis:

1. To identify underlying dimensions called Factors, that explain the correlations among
a set of variables.

e.g lifestyle statements may be used to measure the psychographic profile of consumers

2. To identify a new, smaller set of uncorrelated variables to replace the original set of
correlated variables for subsequent analysis such as Regression or Discriminant
Analysis.

e.g psychographic factors may be used as independent variables to explain the difference
between loyal and non-loyal customers

Types of Factor Analysis:

Exploratory FA:

1. Summarizing data by grouping correlated variables

2. Investigating sets of measured variables related to theoretical constructs

3. Usually done near the onset of research

Confirmatory FA:

1. More advanced technique

2. When factor structure is known or at least theorized

3. Testing generalization of factor structure to new data, etc.

80
Assumptions:

1. Models are usually based on linear relationships

2. Models assume that the data collected are interval scaled

3. Multicollinearity in the data is desirable because the objective is to identify interrelated

set of variables

4. The data should be amenable for factor analysis. It should not be such that a variable
is only correlated with itself and no correlation exists with any other variables. This is
like an Identity Matrix. Factor analysis cannot be done on such data

SAMPLE SIZE:

Minimum numbers of variable for FA is 5 cases per variable

e.g. 20 variables should have>100 cases(1:5)

Factor analysis in Psychology:

➢ Charles Spearman pioneered the use of factor analysis in the field of psychology and
is sometimes credited with the invention of factor analysis

➢ He discovered that school children's scores on a wide variety of seemingly unrelated

subjects were positively correlated, which led him to postulate that a general mental
ability, or g, underlies and shapes human cognitive performance

➢ His postulate now enjoys broad support in the field of intelligence research, where it is
known as the g theory.

➢ Raymond Cattell expanded on Spearman's idea of a two-factor theory of intelligence

after performing his own tests and factor analysis. He used a multi-factor theory to
explain intelligence.

➢ His research led to the development of his theory of fluid and crystallized intelligence,
as well as his 16 Personality Factors theory of personality

Applications in psychology:

➢ Factor analysis is used to identify "factors" that explain a variety of results on different
tests

➢ For example, intelligence research found that people who get a high score on a test of
verbal ability are also good on other tests that require verbal abilities

➢ Researchers explained this by using factor analysis to isolate one factor, often
called crystallized intelligence or verbal intelligence, which represents the degree to
which someone is able to solve problems involving verbal skills.

➢ Factor analysis in psychology is most often associated with intelligence research.

➢ However, it also has been used to find factors in a broad range of domains such as
personality, attitudes, beliefs, etc

➢ It is linked to psychometrics, as it can assess the validity of an instrument by finding if

the instrument indeed measures the postulated factors.

81
Advantages:

• Reduction of number of variables, by combining two or more variables into a single

factor. For example, performance at running, ball throwing, batting, jumping and weight
lifting could be combined into a single factor such as general athletic ability

• Usually, in an item by people matrix, factors are selected by grouping related items

• In the Q factor analysis technique, the matrix is transposed, and factors are created by
grouping related people: For example, liberals, libertarians, conservatives and
socialists, could form separate groups.

• Identification of groups of inter-related variables, to see how they are related to each
other

Disadvantages:

• Factor analysis can be only as good as the data allows. In psychology, where
researchers often have to rely on less valid and reliable measures such as self-reports,
this can be problematic

• Interpreting factor analysis is based on using a "heuristic", which is a solution that is

"convenient even if not absolutely true"

• More than one interpretation can be made of the same data factored the same way,
and factor analysis cannot identify causality.

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 What is incidence and prevalence? what are different types of
prevalence? discuss briefly their significance

Introduction:

Measures of disease frequency are used to describe how common an illness (or other health
event) is with reference to the size of the population (the population at risk) and a measure of
time

2 main measures of disease frequency are:

1. Prevalence: Measures existing cases of disease and is expressed as a proportion

2. Incidence: Measures new cases of disease and is expressed in person-time units

Prevalence

➢ The prevalence represents existing cases of a disease and can be seen as a measure
of disease status; it is the proportion of people in a population having a disease

➢ Prevalence= Number of subjects having the disease at a time point

▪ Total number of subjects in the population

➢ The prevalence is often useful as it reflects the burden of a disease in a certain

population

➢ This is not limited to burden in terms of monetary costs; it also reflects burden in terms
of life expectancy, morbidity, quality of life, or other indicators

➢ Knowledge of the burden of disease can help decision makers to determine where
investments in health care should be targeted

➢ For instance, the prevalent number of end-stage renal disease (ESRD) patients
predicts the need for dialysis facilities and the related costs

➢ There are two main measures of prevalence:

1. Point prevalence:

The proportion of individuals with the condition at a specified point in time

Point Prevalence = Number of people with disease at a given point of time

Number of people in the population at the same point of time

Example:

Of 10,000 adults in town A, on 1st June 2007, 2,000 have depression. The prevalence of
depression among adults in town A on June 1st, 2007 is = 2,000/10,000 = 0.2 or 20%

2. Period Prevalence:

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The proportion of individuals with the condition at any time during a specified time period or
interval

Period Prevalence= Number of people with the condition in a given period of time

Number of people in the population during same period of time

Example:

In 2012, the 12-month prevalence for major depressive episode among U.S. adults was 6.9%.

• Incidence:

Number of new cases of a disease (or other health outcome of interest) that develops in a
population at risk during a specified time period

There are two main measures of incidence:

Incidence rate:

➢ It is related to a measure of the population at risk during the study period

➢ Number of new cases within a specified time period divided by the person-time
at risk during the time period

➢ It is measured in person-time units

Incidence = Number of people who develop disease in a specific time period

Rate Person-time units at risk during the follow-up period

Example:

11 new cases of autism are diagnosed in a community during 2007. In June, the population
of the community is 100,000 people.

Incidence rate = 11 cases/100,000 persons x 1 year

= 11/100,000 person-years, or, 1 per 10,000 person-years

Incidence risk/ Cumulative incidence:

➢ It is related to the population at risk at the beginning of the study period

➢ Proportion of individuals in a population (initially free of disease) who develop

the disease within a specified time interval

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 ➢ Incidence = Number of people who develop disease in a specific time period
Risk Number of disease-free persons at beginning of that time period

Example:

100 people in a closed population (i.e. adds no new members over time) are observed for a
2-year period. 2 develop autism during this period. The 2-year cumulative incidence of autism
in this population is= (2/100)*100= 2 per 100 persons or 2%.

Relation between Prevalence and Incidence

Reference:

Marlies Noordzij, Friedo W. Dekker, Carmine Zoccali, Kitty J. Jager. Measures of Disease
Frequency: Prevalence and Incidence. Nephron Clin Pract 2010;115:c17–c20.

85
 Non-parametric statistics

Non-Parametric tests

➢ Many of the tests that are used for analyses of data have a presumption that data
must have a normal distribution. When the data does not meet normal distribution,
Non-Parametric tests are used

➢ These are those tests that don’t have any presumption about data

➢ These work with Median, which is a much more flexible statistic because it is not
affected by outliers

➢ Advantages of non-parametric tests:

1. Area of study is better represented by median. That is median better represents

the centre of distribution.

2. When the sample size is small. With small sample size it is not possible to
ascertain the distribution of data, so the parametric tests lack sufficient power
to provide meaningful results.

3. Presence of outliers. Parametric test can only assess continuous data and the
results can be significantly affected by outliers.

Parametric test Non-Parametric test

Testing a mean One sample Sign test

t test

Comparison of means of 2 Independent sample t test Mann Whitney U test

unrelated groups

Comparison of means of 2 Paired t test Wilcoxon Signed rank test

related samples

Comparison of means of > ANOVA Kruskal Wallis test

2 unrelated samples

Comparison of means of > Repeated measures of Friedman’s test

2 related samples ANOVA

Assessing the relationship Pearson’s

Spearman’s correlation
between 2 quantitative
Correlation
variables

Chi Square test

➢ It is developed by Karl Pearson.

86
 ➢ It is a non-parametric test of significance not based on any assumption/ distributions
of any variable.

➢ It is applied to sets of categorical data to evaluate hoe likely it is that any observed
difference between the sets arose by chance. It is based on frequencies and not on
parameters like mean and SD

➢ It is statistical hypothesis test in which the sampling distribution of the test statistic is a
chi square distribution when null hypothesis is true

➢ Uses: there are three important uses of chi square test

1. Test of association

2. Test of goodness of fit of distribution

3. Test of proportions

Assumptions for applying chi square test:

1. Random sample

2. Data must be in the form frequencies

3. Frequency data must have a precise numerical value and organised into
groups

4. All the in the sample must be independent

5. Lowest expected frequency should not be less than 5

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

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 Normal distribution and standard deviation

Normal distribution

➢ Also called as Bell-shaped curve or Gaussian distribution, after the well-known

mathematician Karl Freidrich Gauss

➢ It is the most common and widely used continuous distribution

➢ Bell shaped curve can be obtained by compiling data into a frequency table and
graphing it in a histogram

➢ Normal distribution is easy to work with mathematically

➢ In many practical cases, the methods developed using normal theory work well even
when the distribution is nearly normally distributed

➢ Standard normal distribution (Z distribution), is used to find probabilities and

percentiles for regular normal distributions

➢ It serves as a standard by which all other normal distributions are measured

➢ It is a normal distribution with mean “0” and standard deviation of “1”

➢ Properties of the standard normal curve

➢ Its shape is symmetric

➢ Area of the curve is greatest in the middle, where there hump and thins out towards
the tails

➢ It has mean denoted by μ (mu) and standard deviation denoted by б (sigma)

➢ Total area under the curve is equal to 1

➢ Property of the curve is mean= median= mode, this is because the shape of the data
is symmetrical with one peak

➢ Because of bell shape, probabilities for the normal distribution follow the empirical rule.
About 68% of values lie within 1 SD of mean, 95% of values lie within 2 SD of mean
and almost its entire values (about 99.7%) lie within 3 SDs of the mean

➢ There is a strong correlation between the size of a sample n and the extent to which a
sampling distribution approaches the normal distribution

Importance in statistics:

1. All the inferential statistics like correlation, regression, t test and ANOVA are based
on the assumptions that the data follows a normal distribution

2. It is assumed that the samples taken are normally distributed

3. The once which do not use these properties are called Non-parametric tests

4. It is important to check whether the given data follows a normal distribution or not

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 5. If it does not, then parametric test cannot be used

Tests to check normal distribution:

1. By measuring central tendency, skewness, kurtosis

2. Graphical representation of the data

3. Tests like Kolmogorov-Smirnov test, Shapiro-Wilk test etc

If data is not normally distributed, the data can be transferred so that parametric test can be
applied. It can be done by log transformation or square root transformation

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

89
 Applied statistics of Pearson correlation co- efficient

Introduction:

➢ Correlation is a measure of the relation between two or more variables

➢ Correlation coefficients can range from -1.00 to +1.00

➢ The value of -1.00 represents a perfect negative correlation while a value of +1.00
represents a perfect positive correlation

➢ A value of 0.00 represents a lack of correlation

➢ Represented by ‘r’

➢ Types:

1. Pearson /Linear/Product moment corelation

2. Spearman /Nonlinear

PEARSON /LINEAR/PRODUCT MOMENT CORELATION:

➢ Despite its name, it was first introduced by Francis Galton in the 1880s

➢ The most widely-used type of correlation coefficient is Pearson r, also called

linear or product- moment correlation.

➢ For a population

Pearson's correlation coefficient when applied to a population is commonly represented by the

Greek letter ρ (rho) and may be referred to as the population correlation coefficient or
the population Pearson correlation coefficient. The formula for ρ is:

ρ x,y = Cov(X,Y)

σX σY

where:

• Cov is the covariance

• σX' is the standard deviation of X

• σY is the standard deviation of Y

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Interpretation:

1. The correlation coefficient ranges from −1 to 1. A value of 1 implies that a

linear equation describes the relationship between X and Y perfectly, with
all data points lying on a line for which Y increases as X increases

2. A value of −1 implies that all data points lie on a line for which Y decreases
as X increases

3. A value of 0 implies that there is no linear correlation between the variables

• Pearson correlation (hereafter called correlation), assumes that the two variables are
measured on at least interval scales and it determines the extent to which values of
the two variables are "proportional" to each other

• The value of correlation (i.e., correlation coefficient) does not depend on the specific
measurement units used; for example, the correlation between height and weight will
be identical regardless of whether inches and pounds, or centimeters and kilograms
are used as measurement units

• Proportional means linearly related; that is, the correlation is high if it can be
"summarized" by a straight line (sloped upwards or downwards)

• This line is called the regression line or least squares line, because it is determined
such that the sum of the squared distances of all the data points from the line is the
lowest possible

Interpretation of the Values of Correlations:

o The correlation coefficient (r) represents the linear relationship between two
variables

o If the correlation coefficient is squared, then the resulting value (r2, the
coefficient of determination) will represent the proportion of common variation
in the two variables (i.e., the "strength" or "magnitude" of the relationship)

o In order to evaluate the correlation between variables, it is important to know

this "magnitude" or "strength" as well as the significance of the correlation

Significance of Correlations:

• The significance level calculated for each correlation is a primary source of information
about the reliability of the correlation

• The significance of a correlation coefficient of a particular magnitude will change

depending on the size of the sample from which it was computed

• The test of significance is based on the assumption that:

91
 1. The distribution of the residual values (i.e., the deviations from the regression
line) for the dependent variable y follows the normal distribution

2. The variability of the residual values is the same for all values of the
independent variable x.

PROBLEMS WITH PEARSONS COEFFICEIENT

1.Outliers:

➢ Outliers are atypical (by definition), infrequent observations

➢ Because of the way in which the regression line is determined (especially the
fact that it is based on minimizing not the sum of simple distances but the sum
of squares of distances of data points from the line), outliers have a profound
influence on the slope of the regression line and consequently on the value of
the correlation coefficient

➢ A single outlier is capable of considerably changing the slope of the regression

line and, consequently, the value of the correlation, as demonstrated in the
following example.

➢ Needless to say, one should never base important conclusions on the value of
the correlation coefficient alone (i.e., examining the respective scatterplot is
always recommended)

2. Nonlinear Relations between Variables:

➢ Another potential source of problems with the linear (Pearson r) correlation is

the shape of the relation

➢ As mentioned before, Pearson r measures a relation between two variables

only to the extent to which it is linear; deviations from linearity will increase the
total sum of squared distances from the regression line even if they represent
a "true" and very close relationship between two variables

➢ The possibility of such non-linear relationships is another reason why

examining scatterplots is a necessary step in evaluating every correlation

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3. Spurious Correlations:

➢ Although you cannot prove causal relations based on correlation coefficients,

you can still identify so-called spurious correlations; that is, correlations that are
due mostly to the influences of "other" variables

➢ For example, there is a correlation between the total amount of losses in a fire
and the number of firemen that were putting out the fire; however, what this
correlation does not indicate is that if you call fewer firemen then you would
lower the losses

➢ There is a third variable (the initial size of the fire) that influences both the
amount of losses and the number of firemen.

➢ If you "control" for this variable (e.g., consider only fires of a fixed size), then
the correlation will either disappear or perhaps even change its sign.

➢ The main problem with spurious correlations is that we typically do not know
what the "hidden" agent is.

➢ However, in cases when we know where to look, we can use partial correlations
that control for (partial out) the influence of specified variables.

4. Are correlation coefficients "additive?"

➢ No, they are not

➢ For example, an average of correlation coefficients in a number of samples

does not represent an "average correlation" in all those samples

➢ Because the value of the correlation coefficient is not a linear function of the
magnitude of the relation between the variables, correlation coefficients cannot
simply be averaged

➢ In cases when you need to average correlations, they first have to be converted
into additive measures

➢ For example, before averaging, you can square them to obtain coefficients of
determination which are additive (as explained before in this section), or
convert them into so-called Fisher z values, which are also additive

5. How to Determine Whether Two Correlation Coefficients are Significant:

• A test is available that will evaluate the significance of differences between two
correlation coefficients in two samples.

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• The outcome of this test depends not only on the size of the raw difference
between the two coefficients but also on the size of the samples and on the
size of the coefficients themselves.

• Consistent with the previously discussed principle, the larger the sample size,
the smaller the effect that can be proven significant in that sample.

• In general, due to the fact that the reliability of the correlation coefficient
increases with its absolute value, relatively small differences between large
correlation coefficients can be significant.

94
 What is qualitative research? essential features, strengths and
limitations of qualitative research? Importance of Quantitative research
in Psychiatry

I. Introduction:

Qualitative research:

➢ A form of social inquiry that focuses on the way people interpret and make sense of
their experiences and the world in which they live

➢ Qualitative research can provide insight which is not possible to elucidate with purely
quantitative data like:

1. A means for exploring and understanding the meaning individuals or groups

ascribe to social or human problems

2. Study human behaviour and social world

➢ It helps us to understand the world in which we live and why things are the way they
are

Qualitative research answer questions on:

➢ Why people behave the way they do

➢ How opinions and attitudes are formed
➢ How people are affected by the events that go on around them
➢ How and why cultures have developed
➢ The difference between social groups
Sr Qualitative research Quantitative research
No.
1. Subjective Objective
Concern with opinion, experience and
feelings of individuals
2. Holistic Reductionist- identify a set of variables
3. Phenomenological Scientific
4. Descriptive Experimental
5. Naturalistic Contrived
6. Inductive – General theories Deductive- Test proposed theories
7. Small sample- Representative sample
Direct data collection, interview,
observation
8. Results- Generalizability is not an aim Usually generalizability is an important aim

II. Four major types of qualitative research design include:

1. Phenomenology

2. Ethnography

95
 3. Grounded theory

4. Case study

1. Phenomenology:

➢ Study of a phenomena – describing something that exist as part of the world

➢ Phenomena might be:

• An event, a situation, an experience or a concept

• e.g. back pain

➢ It begins with the acknowledgment that there is a gap in our understanding

➢ It may not necessarily provide definitive explanations, but it does raise awareness
and increase insight

2. Ethnography:

➢ The term means “portrait of people”

➢ It is a methodology for descriptive studies of cultures and people

➢ e.g. cultural parameter is suspected of affecting the population’s response to care

or treatment

➢ It requires extensive fieldwork by the researchers

➢ Data collection includes formal and informal interview on several occasion and
observation

➢ It is extremely time consuming

➢ These studies might be problematic when researchers are not familiar with social
norms and language

3. Grounded theory:

➢ Main feature: development of a new theory through the collection and analysis of
data about a Phenomenon

➢ It goes beyond phenomenology as the explanation are genuinely new knowledge

and are used to develop theories

➢ Various data collection techniques are used

➢ Literature review, documentary analysis, interviews, observation

III. Methods of collecting qualitative data:

1. Direct interaction with individuals

2. One to one interaction Or interaction with a group

96
 3. Interviews

4. Focus Group Discussion

5. Observation

Data collection is time consuming

Benefits of these methods include richness of data and deeper insight into phenomena under
study

1. Interviews:

➢ Structured interviews:

• Same questions in same away

• Limited range of responses (e.g. questionnaires)

➢ Semi structured interviews or focused interviews:

• Series of open ended questions

• Provide opportunities to both researchers and respondents to discuss certain

topics in more details

➢ Unstructured interviews or in-depth interviews:

• Discussing limited number of topics

• Phrase questions in the interviewee’s previous response

➢ Qualitative interviews are semi structure or unstructured

➢ Qualitative interviews should be fairly informal

➢ Require careful consideration and preparation

2. Focused group discussion:

➢ Collect information from groups of people rather than a series of individuals

➢ FGD can be used when:

✓ Resources are limited

✓ To identify a number of individuals who share a common factor

✓ It is desirable to collect the views of several people within the population

sub group

✓ Group interaction among participants has the potential for greater

insights to be developed

➢ Characteristics of a focus group:

✓ Group size: usually 6-10 people

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 ✓ Several FGD should be run in any research, it would be wrong to rely on the
views of just one group

✓ Members of each group should have something in common

✓ May use pre-formed groups e.g. pressure groups

➢ Data collection and analysis is time consuming

➢ Requires certain skills e.g Facilitation, moderating, listening, observing and

analysing

3. Observation:

Might be the only method to collect information in certain conditions

Observation of people VS. observation of environment

Observation can also serve for verifying or nullifying information collected through other
methods

Techniques for collecting data:

➢ Written descriptions

• Researcher may miss to record

• May focus on one thing and miss equally or even more important things

➢ Video recording:

• No need to take notes

• Review time after time

• Recording my affect, the behaviour of the people under observation

• Fixed camera may limit the range of possible observation

➢ Photographs:

• Good way of collecting observable data of phenomena which can be captured

in a single shots or series of shots

• Photographs of buildings, neighborhoods, dress and appearance

➢ Documentation:

• Wide range of written materials

• Policy document, annual reports, minutes of meeting, codes of conduct, notice

boards etc

IV. Analysing qualitative data:

➢ Involves summarizing data and presenting the results in a way that communicate
the most important features

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 ➢ As quantitative research it is important to discover the big picture in qualitative
research as well, but by using different technics

➢ We start labeling or coding every item of information to recognize differences and

similarities between all different items

➢ No system for pre-coding

➢ Needs a method of identifying and coding items of data which appear in the text of
transcript

➢ All the items of data from one interview should be compared with other interviews

➢ Same procedures are used for qualitative data collected through interviews,
FGDs, observation and documentary analysis – since all are concerned with
analyzing text

Content analysis:

➢ Procedure for categorization of verbal or behavioral data

➢ It involves coding and classifying data

Analysis done at two levels:

• Basic or manifest level: descriptive – what was actually said

• Higher or interpretative level: what was meant by response – also called latent level of
analysis

V. Presenting the results of qualitative research:

➢ Look at themes and categories and structure the results accordingly

➢ The structure can be set out at the beginning as a list or diagram

➢ Themes are the main findings of the study

➢ To support findings, evidence are presented at direct quotations from respondents

➢ A range of quotations should be selected:

1. Strength of opinion or belief

2. Similarities between respondents

3. Differences between respondents

4. Link between different categories

VI. Strengths of Qualitative research:

✓ Aims to understand meaning

✓ Interpretation in particular settings, situations and conditions

✓ Rigorous and systematic data collection and analysis often occur concurrently

✓ Data rich in descriptions

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 ✓ Concepts derived from the data itself

✓ Aims to explore and communicate

✓ Aims at hypothesis generation

VII.Challenges:

✓ Small scale

✓ Non-representative samples

✓ Bias

✓ Access to samples

✓ Time consuming

✓ Record keeping

✓ Relationships between the researcher and the researched

✓ Subjectivity

✓ Reliability

✓ Verification

✓ Difficulty in studying large populations

Acknowledgement:

Najibullah Safi, MD. MSc. HPM, NPO/PHC, WHO Afghanistan

100
 Randomized controlled Trial

1. Historical aspects:

➢ First reported clinical trial - conducted by James Lind(1747), to identify treatment

for Scurvy

➢ First published RCT in medicine – Streptomycin treatment of

pulmonary tuberculosis, 1948

➢ Austin Bradford Hill – credited as having conceived the modern RCT

➢ Late 20th century – RCTs recognized as the standard method for "rational
therapeutics" in medicine

2. Principles of RCT:

➢ RCT is a trial in which subjects are randomly assigned to one of two groups:

1. One (the experimental group) receiving the intervention that is being tested

2. The other (the comparison group or control) receiving an alternative

(conventional) treatment

➢ The two groups are then followed up to see if there are any differences between
them in outcome

➢ The results and subsequent analysis of the trial are used to assess the
effectiveness of the intervention

➢ RCTs are the most stringent way of determining whether a cause-effect relation
exists between the intervention and the outcome

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3. RCT Classification:

➢ By study design –

1. Concurrent parallel design

2. Cross-over design:

• Experimental & reference groups are crossed over (exposed group

becomes non-exposed & vice-versa)

• Reduces ethical concerns

➢ By Hypothesis (Superiority vs. Non-inferiority vs. Equivalence)

➢ By outcome of interest (efficacy vs. Effectiveness)

1. Explanatory –

Test efficacy in a research setting with highly selected participants and under highly controlled
conditions

2. Pragmatic RCT –

Test effectiveness in everyday practice with relatively unselected participants and under
flexible conditions

Can "Inform decisions about practice"

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4. Types of Bias in RCT:

❑ Selection bias:

• Error introduced when the study population does not represent the target population

❑ Information bias:

• Occurs during data collection

❑ Confounding:

• Factor associated with both exposure and outcome, and has an independent effect in
causation of outcome

5. Randomisation:

 The random assignment of subjects into one of two groups is the basis for establishing
a causal interpretation for an intervention

 Effective randomisation will minimise confounding variables that exist at the time of
randomisation

 Randomisation must be concealed from the investigator

 Analysis of results should occur based on the initial randomisation, irrespective of what
may subsequently actually have happened to the subject (i.e., “intention to treat
analysis”)

Types of randomisation:

 Types -

1. Simple

2. Block

3. Stratified

4. Cluster

 Methods -

1. Random number tables

2. Computer software

3. Lottery method

6. Allocation concealment:

 Procedure for protecting the randomization process so that the treatment to be

allocated is not known before the patient is entered into the study

 Standard methods –

❑ Sequentially numbered, opaque, sealed envelopes (SNOSE)

❑ Sequentially numbered containers

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 ❑ Pharmacy controlled randomization

❑ Central randomization

7. Blinding:

 Procedures that prevent study participants, caregivers, or outcome assessors from

knowing which intervention was received

 Blinding at the stage of applying the intervention and measuring the outcome is
essential if bias (intentional or otherwise) is to be avoided

 The subject and the investigator should ideally be blinded to the assignment (double
blind)

 Blinding is achieved by making the intervention and the control appear similar in every
respect

 Blinding can break down for various reasons, but this can be systematically assessed

8. Features of a well-designed RCT:

 The sample to be studied will be appropriate to the hypothesis being tested so that any
results are appropriately generalisable

 The study will recruit sufficient patients to allow it to have a high probability of detecting
a clinically important difference between treatments if a difference truly exists

 There will be effective (concealed) randomisation of the subjects to the

intervention/control groups (to eliminate selection bias and minimise confounding
variables)

 The sample to be studied will be appropriate to the hypothesis being tested so that any
results are appropriately generalisable.

 The study will recruit sufficient patients to allow it to have a high probability of detecting
a clinically important difference between treatments if a difference truly exists

 There will be effective (concealed) randomisation of the subjects to the

intervention/control groups (to eliminate selection bias and minimise confounding
variables)

 The sample to be studied will be appropriate to the hypothesis being tested so that any
results are appropriately generalisable.

 The study will recruit sufficient patients to allow it to have a high probability of detecting
a clinically important difference between treatments if a difference truly exists

 There will be effective (concealed) randomisation of the subjects to the

intervention/control groups (to eliminate selection bias and minimise confounding
variables)

9. LIMITATIONS:

 External validity may be limited

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  Time and costs

 Conflict of interest dangers

 Ethical issues

Reference:

Peter Peduzzi, William Henderson, Pamela Hartigan, Philip Lavori. Analysis of Randomized
Controlled Trials. Epidemiol Rev Vol. 24, No. 1, 2002

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 Define reliability of a test instrument in Psychiatry. What are the
different types of reliability and how are they measured? Inter-rater
reliability

Reliability:

Definition:

1. Reliability refers to the ability of a measurement instrument to produce the

same result on repeated measurement

2. Reliability refers to the consistency of scores obtained by the same persons

when re-examined with the same test on different occasions, or with different
sets of equivalent items, or under other variable examining conditions
(Anastasi, 1990)

3. It indicates the extent to which individual differences in test scores are

attributable to “true” differences in the characteristics under consideration and
the extent to which they are attributable to chance errors

4. A valid measurement or a system is reliable by definition

5. There is no guarantee that a reliable system is also valid

Types of reliability:

1. Scorer/ Inter-rater reliability:

➢ It refers to ability of measurement instrument to produce the same result when

administered by two different raters

➢ It is the probability that 2 raters:

(i) will give the same score to given answer

(ii) rate a given behaviour in the same way

(iii) add up the score properly

➢ Scorer reliability should be near perfect

2. Test-Retest reliability:

➢ It assesses the ability of a measurement to arrive at the same result for the
same subject on repeated administrations

➢ The interval between the test and retest should be long enough to ensure that
the person’s responses are based on his/ her current condition rather than the
memory of responses in the first test administration

➢ If there is too long, there is a risk that the person’s condition may have changed

3. Parallel form reliability:

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 ➢ It refers to the degree to which two equivalent versions of a test give the same
result

➢ This type of reliability is usually used when a test cannot be exactly repeated.

4. Split half reliability:

➢ If a test cannot be repeated or if there is no parallel form, a test can be split in

two and these two halves are correlated with each other. For e.x odd vs even
items

➢ There is a mathematical formula for computing the mean of all possible split
halves.

5. Internal consistency:

➢ The degree to which one test item correlates with all other test items

➢ It is denoted by α co-efficient

➢ It should not drop below 0.7

• Psychometric tests aim to measure a real quantity

• Real quantity is true score (t), score obtained on test is observed score (x)

• As no test is perfect, there is error (e)

• Aim is to reduce ‘e’ to minimum to make as reliable as possible

• In practice, when the test is repeated, each occasion will give different score,
i.e. observed score will cluster around true score

• If reliability of the test is perfect, real score= observed score (t=e)

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

107
 What is sample? how will you select an appropriate sample for an
epidemiological study?

Sampling:

Introduction:

➢ Sampling is a process used in statistical analysis in which a predetermined number of

observations will be taken from a larger population

➢ A population includes all people/ items with the characteristic one wishes to understand

➢ Because there is very rarely enough time or money to gather information from
everyone/ everything in a population, the goal becomes finding a representative
sample of that population

➢ Probability sampling:

1. Every unit in the population has a chance of being selected in the sample

2. This makes it possible to produce unbiased estimates of population

3. It includes simple, Systemic, Stratified and Cluster sampling

➢ Non-probability sampling:

1. Some elements of the population have no chance of selection

2. It involves the selection of elements based on assumptions regarding the

population of interest, which forms the criteria for selection

3. It includes Quota, Purposive and Convenience sampling

Types of sampling techniques

1. Simple random sampling:

➢ Each element in the population has an equal probability of selection and each
combination of elements has an equal probability of selection

➢ Numbers are drawn out by lottery technique

2. Systematic random sampling:

➢ Relies on arranging the study population according to some ordering scheme and then
selecting elements at regular intervals

➢ It involves a random start and then proceeds with selection of every kth element from
then on

➢ It is less accurate than simple random sampling

3. Stratified sampling:

➢ When a population has a number of distinct categories, the frame can be organised by
these categories into separate ‘starta’

108
 ➢ Each stratum is then sampled as an independent sub population, out of which
individual elements can be randomly selected

4. Cluster sampling:

➢ Sometimes it becomes impossible/ impractical to create a sampling frame of a target

population, and/ or the target population is widely dispersed geographically, making
data collection costs relatively high. In such cases, cluster sampling would be ideal

➢ A cluster is an aggregate or intact grouping of population

➢ This type of sampling involves random selection of items from clusters

➢ Clusters may be space based, such as naturally occurring geographical/ physical units;
organisation based like districts, schools, grades etc.

➢ Heterogeneity of the cluster is central to a good cluster sample design. Ideally, within
cluster difference should be high and between cluster difference should be low

➢ It is commonly implemented in multistage sampling

5. Quota sampling:

➢ This is similar to stratified sampling, but instead of randomisation, quota is used in

selecting the sample

6. Purposive sampling:

➢ Sample is selected based on the purpose of the research

➢ Here the researcher believes that the sample selected serves the purpose of the
research

➢ It has big sampling errors and carry misleading conclusions

7. Convenience sampling:

➢ Sample is selected because it is easy to assess/ collect them

➢ No reason tied to the purpose of research

8. Snowball sampling:

➢ Sociometric sampling technique generally used to study the small group

➢ All the persons in a group identify their friends who in turn identify their friends and
colleagues, until the informal relationships coverage into some type of a definite social
pattern

➢ It is just like snowball increasing in size as it goes on rolling in ice field

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

109
 Standard deviation

Introduction:

1. The standard deviation (often SD) is a measure of variability

2. When we calculate the standard deviation of a sample, we are using it as an estimate

of the variability of the population from which the sample was drawn

3. For data with a normal distribution, about 95% of individuals will have values within 2
standard deviations of the mean, the other 5% being equally scattered above and
below these limits

4. SD is a special form of average deviation from the mean

5. It is the positive square root of the arithmetic mean of the squared deviations from the
mean of the distribution

Formula for SD:

Calculation of SD:

1. Find the Mean

2. Calculate the difference between each score and the Mean

3. Square the difference between each score and the mean

4. Add up all the squares of the difference between each score and the mean

5. Divide the obtained sum by n– 1

6. Extract the positive square root of the obtained quotient

Characteristics of SD:

1. The standard deviation is affected by the value of every observation

2. The process of squaring the deviations before adding avoids the algebraic
fallacy of disregarding the signs

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 3. It has a definite mathematical meaning and is perfectly adapted to algebraic
Treatment

4. It is, in general, less affected by fluctuations of sampling than the other

measures of dispersion

5. The standard deviation is the unit customarily used in defining areas under the

normal curve of error. It has, thus, great practical utility in sampling and statistical inference

111
 Student t test

Student t-test:

➢ Developed by WS Gosset, a chemist working for the Guinness brewery in Dublin,

Ireland ("Student" was his pen name)

➢ It can be used to determine if two sets of data are significantly different from each other

➢ A t-test is any statistical hypothesis test in which the test statistic follows a Student's t
distribution if the null hypothesis is supported

➢ The t-distribution is similar to standard normal distribution, but it’s shorter and flatter
than the standard normal distribution (Z distribution). But as the sample size increases
(degrees of freedom) the t distribution approaches the standard normal distribution

➢ Degree of freedom is always a simple function of sample size that is (n-1)

➢ Particular advantage of the t-test is it does not require any knowledge of the population
standard deviation

➢ So it can be used to test hypothesis of a completely unknown population, and the only
available information about the sample comes from the sample

➢ All that is required for a hypothesis test with t-test is a sample and a reasonable
hypothesis about the population mean

➢ Types of Student t-test:

1.One sample t-test:

only one group and typically used to compare a sample mean to a known population mean.
E.g. a group of schizophrenic patients were assessed on cognitive tests and the group is
compared with the population

2.Paired/ Dependent sample t-test:

There are two groups and two means which are related to each other. Like two scores for
each person, or when there are matched scores. E.g. a sample is tested to see the metabolic
side effects before and after treatment. Before and after sample are compared to see any
difference

3.Unpaired/ Independent/ two sample t-test:

There are two means, two groups and not related to each other. Used to compare means from
independent groups. E.g. two sample of patients one given a placebo and another newer anti-
psychotic both were compared to see the utility of newer antipsychotic.

112
Assumptions:

1. Data must come from a population that follows a normal distribution.

2. For two sample t-test, the two populations must have equal variances. If variances are not
equal then Wlech’s t-test is used.

3. Each score must be independent of all other scores

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

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 What is the difference between meta -analysis and systematic
review? describe two metanalysis studies / Metanalysis

Introduction:

➢ The need to arrive at decisions affecting clinical practise fostered the

momentum toward evidence-based medicine.

➢ Evidence-based medicine may be defined as the systematic, quantitative,

preferentially experimental approach to obtaining and using medical
information

➢ Therefore, meta-analysis, a statistical procedure that integrates the results of

several independent studies, plays a central role in evidence-based medicine

Meta-Analysis

Systematic Review

RCT

Cohort Studies

Case Control studies

Case series/Case
reports
Animal
research

Hierarchy of Evidence

Meta-Analysis:

➢ Glass first defined meta-analysis in the social science literature as “The statistical
analysis of a large collection of analysis results from individual studies for the purpose
of integrating the findings”.

➢ Meta-analysis is a quantitative, formal, epidemiological study design used to

systematically assess the results of previous research to derive conclusions about that
body of research.

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 ➢ Typically, but not necessarily, the study is based on randomized, controlled clinical
trials

➢ Outcomes from a meta-analysis may include a more precise estimate of the effect of
treatment or risk factor for disease, or other outcomes, than any individual study
contributing to the pooled analysis

➢ Identifying sources of variation in responses; that is, examining heterogeneity of a

group of studies, and generalizability of responses can lead to more effective
treatments or modifications of management

➢ Examination of heterogeneity is perhaps the most important task in meta-analysis

➢ The Cochrane collaboration has been a long-standing, rigorous, and innovative leader
in developing methods in the field

➢ Useful guide to improve reporting of systematic reviews and meta-analyses is the

PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses)
statement that replaced the QUOROM (QUality Of Reporting of Meta-analyses)
statement

Systematic review:

➢ Meta-analyses are a subset of systematic review

➢ A systematic review attempts to collate empirical evidence that fits prespecified

eligibility criteria to answer a specific research question

➢ The key characteristics of a systematic review are:

✓ A clearly stated set of objectives with predefined eligibility criteria for studies

✓ An explicit, reproducible methodology

✓ A systematic search that attempts to identify all studies that meet the eligibility
criteria

✓ An assessment of the validity of the findings of the included studies (e.g., through
the assessment of risk of bias)

✓ A systematic presentation and synthesis of the attributes and findings from the
studies used

➢ Systematic methods are used to minimize bias, thus providing more reliable findings
from which conclusions can be drawn and decisions made than traditional review
methods

➢ Systematic reviews need not contain a meta-analysis there are times when it is not
appropriate or possible

➢ However, many systematic reviews contain meta-analyses

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Systematic review vs Meta- Analysis:

“Systematic review” will refer to the entire process of collecting, reviewing, and presenting all
available evidence, while the term “meta-analysis” will refer to the statistical technique involved
in extracting and combining data to produce a summary result

Aims of metanalysis:

➢ Meta-analyses are conducted to assess the strength of evidence present on a disease

and treatment

➢ One aim is to determine whether an effect exists

➢ Another aim is to determine whether the effect is positive or negative and ideally, to
obtain a single summary estimate of the effect

➢ The results of a meta-analysis can:

✓ Improve precision of estimates of effect

✓ Answer questions not posed by the individual studies

✓ Settle controversies arising from apparently conflicting studies

✓ Generate new hypotheses

➢ In particular, the examination of heterogeneity is vital to the development of new

hypotheses

Steps in doing systematic reviews/meta-analysis

Following are the six fundamental essential steps while doing systematic review and meta-
analysis.

1. Define the question

➢ This is the most important part of systematic reviews/meta-analysis

➢ The research question for the systematic reviews may be related to a major public
health problem or a controversial clinical situation which requires acceptable
intervention as a possible solution to the present healthcare need of the community

➢ This step is most important since the remaining steps will be based on this

2. Reviewing the literature

➢ This can be done by going through scientific resources such as electronic database,
controlled clinical trials registers, other biomedical databases, non-English literatures,
“gray literatures” (thesis, internal reports, non–peer-reviewed journals, pharmaceutical
industry files), references listed in primary sources, raw data from published trials and
other unpublished sources known to experts in the field

➢ Among the available electronic scientific database, the popular ones are PUBMED,
MEDLINE, and EMBASE

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3.Sift the studies to select relevant ones

➢ To select the relevant studies from the searches, we need to sift through the studies
thus identified

➢ The first sift is pre-screening, i.e., to decide which studies to retrieve in full, and the
second sift is selection which is to look again at these studies and decide which are to
be included in the review

➢ The next step is selecting the eligible studies based on similar study designs, year of
publication, language, choice among multiple articles, sample size or follow-up issues,
similarity of exposure, and or treatment and completeness of information

➢ It is necessary to ensure that the sifting includes all relevant studies like the
unpublished studies (desk drawer problem), studies which came with negative
conclusions or were published in non-English journals and studies with small sample
size

4. Assess the quality of studies

➢ The steps undertaken in evaluating the study quality are early definition of study quality
and criteria, setting up a good scoring system, developing a standard form for
assessment, calculating quality for each study, and finally using this for sensitivity
analysis

➢ For example, the quality of a randomized controlled trial can be assessed by finding
out the answers to the following questions:

1. Was the assignment to the treatment groups really random?

2. Was the treatment allocation concealed?

3. Were the groups similar at baseline in terms of prognostic factors?

4. Were the eligibility criteria specified?

5. Were the assessors, the care provider, and the patient blinded?

6. Were the point estimates and measure of variability presented for the primary
outcome measure?

7. Did the analyses include intention-to-treat analysis?

5. Calculate the outcome measures of each study and combine them

➢ We need a standard measure of outcome which can be applied to each study on the
basis of its effect size

➢ Based on their type of outcome, following are the measures of outcome: Studies with
binary outcomes (cured/not cured) have odds ratio, risk ratio; studies with continuous
outcomes (blood pressure) have means, difference in means, standardized difference
in means (effect sizes); and survival or time-to-event data have hazard ratios

6. Combining studies

➢ Homogeneity of different studies can be estimated at a glance from a forest plot

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 ➢ The definitive test for assessing the heterogeneity of studies is a variant of Chi-square
test (Mantel–Haenszel test)

➢ The final step is calculating the common estimate and its confidence interval with the
original data or with the summary statistics from all the studies

➢ The best estimate of treatment effect can be derived from the weighted summary
statistics of all studies which will be based on weighting to sample size, standard
errors, and other summary statistics

➢ Log scale is used to combine the data to estimate the weighting

Interpret results: Graph

➢ The results of a meta-analysis are usually presented as a graph called forest plot
because the typical forest plots appear as forest of lines

➢ It provides a simple visual presentation of individual studies that went into the meta-
analysis at a glance

➢ It shows the variation between the studies and an estimate of the overall result of all
the studies together

Advantages of Systematic Reviews:

Systematic reviews have specific advantages because of using explicit methods which:

➢ Limit bias

➢ Draw reliable and accurate conclusions

➢ Easily deliver required information to healthcare providers, researchers, and

policymakers

➢ Help to reduce the time delay in the research discoveries to implementation

➢ Improve the generalizability and consistency of results

➢ Generation of new hypotheses about subgroups of the study population

➢ Overall, they increase precision of the results

Limitations in Systematic Reviews/Meta-analysis:

➢ As with all research, the value of a systematic review depends on what was done, what
was found, and the clarity of reporting

➢ As with other publications, the reporting quality of systematic reviews varies, limiting
readers’ ability to assess the strengths and weaknesses of those reviews

➢ Even though systematic review and meta-analysis are considered the best evidence
for getting a definitive answer to a research question, there are certain inherent flaws
associated with it such as:

✓ The location and selection of studies

✓ Heterogeneity

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 ✓ Loss of information on important outcomes

✓ Inappropriate subgroup analyses

✓ Conflict with new experimental data

✓ Duplication of publication

Publication Bias:

➢ Publication bias results in it being easier to find studies with a “positive” result

➢ This occurs particularly due to inappropriate sifting of the studies where there is always
a tendency towards the studies with positive (significant) outcomes

➢ This effect occurs more commonly in systematic reviews/meta-analysis which need to

be eliminated

➢ The quality of reporting of systematic reviews is still not optimal

➢ In a recent review of 300 systematic reviews, few authors reported assessing possible
publication bias even though there is overwhelming evidence both for its existence and
its impact on the results of systematic reviews

➢ Even when the possibility of publication bias is assessed, there is no guarantee that
systematic reviewers have assessed or interpreted it appropriately

References:

1. S. Gopalakrishnan and P. Ganeshkumar. Systematic Reviews and Meta-analysis:

Understanding the Best Evidence in Primary Healthcare. J Family Med Prim Care.
2013 Jan-Mar; 2(1): 9–14.

2. Haidich AB. Meta-analysis in medical research. HIPPOKRATIA 2010, 14 (Suppl 1):

29-37.

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 Tests of significance/Measures of statistical significance

Statistics: It is a broad subject, with applications in a vast number of different fields. Generally
speaking it is the methodology of collecting, analysing, interpreting and drawing conclusions
from information. It provides methods for

1. Design: planning and carrying out research studies.

2. Description: summarising and exploring data.

3. Inference: making predictions and generalising about phenomena represented by the

data

Tests of Significance:

➢ They are statistical procedures to draw inferences from samples about population

Need for tests of significance is to find:

1. Whether difference between sample estimate and population values is significant

or not?

2. Whether differences between different sample estimates is significant or not

Steps in Tests of Significance

1. State clearly the Null Hypothesis (Ho)

2. Choose Level of Significance (α)

3. Decide test of Significance

4. Calculate value of test statistic

5. Obtain P-Value

6. Conclude about Null Hypothesis (Ho)

Tests of significance:

A. Parametric Statistics:

These tests should be used when:

➢ The given observations are independent

➢ Observations come from normal distribution

➢ The hypothesis involves population parameters

➢ Parametric procedures may be applied on measurement data only

➢ Computations are sometimes difficult

➢ Parametric procedures are more robust than Non-Parametric procedures

120
 1. Z-test (for large samples) for testing significance of:

➢ Single population means

➢ Difference of two population means

➢ Single population proportion

➢ Difference of two population proportions

2. t-test (for small samples) for testing significance of:

➢ Single population means

➢ Difference of two population means

➢ Paired data (effectiveness of drug)

➢ Correlation coefficient

3. F-Test:

➢ Testing equality of several means

➢ Testing equality of two population variances

➢ One-way, Two-way and Multi-way ANOVA

B. Non-Parametric tests:

Non-parametric tests should be used when:

➢ The given observations are independent

➢ Observations may not be from normal distribution

➢ Based on minimum assumptions

➢ The hypothesis is not concerned about population parameters

➢ Non-Parametric procedures may be applied on weak measurement scale i.e.

on count data or rank data

➢ Computations are simple

1. Chi-square:

There are three important uses of chi square test

i. Test of association

ii. Test of goodness of fit of distribution

iii. Test of proportions

H0: Relative Risk =1 or Odds Ratio =1

2. Sign test: Testing median

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 3. Wilcoxon signed rank test: Testing median

4. Run test: For randomness

5. Median test: For testing equality of two medians

6. Mann-Whitney test: For testing equality of two medians

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

122
 Type I and Type II errors / Discuss about Type I and Type II error in
biostatistics

Types of error

➢ Aim of doing a study is to check whether the data agree with certain predictions. These
predictions are called hypothesis.

➢ Hypothesis arises from the theory that drives the research. These are formulated
before collecting the data.

➢ Hypothesis testing will help to find if variation between two sample distributions can
just be explained through random chance or not. Before concluding that two
distributions vary in a meaningful way, precautions must be taken to see that the
differences are not just through random chance.

➢ There are two types of hypothesis- Null (H0) and Alternative hypothesis (H1)

➢ Null hypothesis is usually a statement that the parameter has value corresponding to,
in some sense, no effect

➢ Alternative hypothesis is a hypothesis which contradicts the null hypothesis

➢ Significance test is a way of statistically testing hypothesis by comparing the data

values

➢ Significance test analyses the strength of sample evidence against the null hypothesis.
The test is conducted to investigate whether the data contradicts the null hypothesis,
suggesting alternative hypothesis is true

➢ p-Value is the probability, if H0 were true, that the test statistic would fall in this
collection of values. The smaller the p-value, the more strongly the data contradicts
H0. When p-value ≤ 0.05, data sufficiently contradicts H0.

Type α/ I error- Rejecting true null hypothesis

1. Leading to conclusion that difference is significant, when in fact there is no real

difference

2. In simple terms, it is asserting something that is absent. It is False Positive

3. For example, a study indicating that a particular treatment cures a disease when in fact
it does not

4. It is popularly known as p-value

5. Maximum p-value allowed is called as level of significance. Being serious p-value is

kept low, mostly less than 5% or p<0.05

6. It means to say that there is only 5 in 100 chances that the variation we are seeing is
due to chance

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Type β/ II error- Accepting false null hypothesis

1. Leading to conclusion that difference is not significant, when in fact there is real
difference

2. It is also called as False Negative

3. For example, a study indicating that a new treatment modality fails to work, when in
fact it does work

4. It is also called as Power of the test & indicates sensitivity of the test

5. Type II error can be decreased by ensuring enough power

➢ All statistical hypothesis tests have a probability of making type I and II errors. These
error rates are traded off against each other. For a given test, the effort to reduce one
type of error generally results in increasing the other type of error

➢ For a given test, one way to reduce the error is to increase the sample size where ever
it is feasible

➢ It is not possible to reduce both type I & II, So α error is fixed at a tolerable limit & β
error is minimized by ↑ sample size.

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

124
 Validity of a test

Validity

Definition: the degree to which a test measures what it is supposed to measure is known as
validity

Types of validity:

1. Face validity:

➢ It refers to whether test seems sensible to the person completing it, i.e. does it appear
to measure what it is meant to be measuring

➢ e.g People might have negative reactions to an intelligence test that did not appear to
them to be measuring their intelligence

2. Content validity:

➢ It refers to the degree to which the test measures all the aspects of the item that is
being assessed

➢ It is the extent to which the measurement method covers the entire range of relevant
behaviors, thoughts, and feelings that define the construct being measured

➢ If test anxiety is thought to include both nervous feelings and negative thoughts, then
any measure of test anxiety should cover both of these aspects

➢ A course exam has good content validity if it covers all the material that students are
supposed to learn and poor content validity if it does not

3. Concurrent validity:

➢ It reveals that at a given point of time, high scorers on a test may be more likely than
low scorers

➢ To determine test’s concurrent validity, external measures are obtained at the same
time that the test is given to the sample of subjects

➢ For example, correlation between HAMD and MADRS in which concurrent validity of
MADRS is checked with HAMD, already established instrument for depression

4. Criterion Validity:

➢ It is the extent to which people’s scores are correlated with other variables or criteria
that reflect the same construct

➢ Example:

An IQ test should correlate positively with school performance

Types of Criterion Validity:

1. Predictive validity:

125
 ➢ It refers to degree to which a test predicts whether some criterion is achieved in future.

➢ Here the external criterion would have to be obtained a number of years down the road
for the test to have the predictive validity.

2. Concurrent Validity:

When the criterion is something that is happening or being assessed at the same time as the
construct of interest, it is called concurrent validity.

5. Construct validity:

➢ It refers to whether a test measures some specified hypothetical construct

➢ If a test is measuring one construct, there should not be cluster of items that seem to
be measuring different things.

6. Factorial validity:

➢ If a test breaks down into various sub-factors then the number and nature of these
factors should remain stable across time and different subject populations.

7. Incremental validity:

➢ It refers whether the test results improve decision making

➢ For example, whether knowledge of neuropsychological test results improves the

detection of brain injury

8. Discriminant Validity:

➢ It is the extent to which people’s scores are not correlated with other variables that
reflect distinct constructs

➢ Example:

1. Imagine, that a researcher with a new measure of self-esteem claims that self-
esteem is independent of mood; a person with high self-esteem can be in either a
good mood or a bad mood (and a person with low self-esteem can too)

2. Then this researcher should be able to show that his self-esteem measure is not
correlated (or only weakly correlated) with a valid measure of mood

3. If these two measures were highly correlated, then we would wonder whether his
new measure really reflected self-esteem as opposed to mood.

9. External Validity:

It is the extent to which the results of a research study can be generalized to different
situations, different groups of people, different settings, different conditions, etc.

10. Internal Validity:

It is basically the extent to which a study is free from flaws and that any differences in a
measurement are due to an independent variable and nothing else

126
Measurement of Validity:

There are some extremely important points to remember about the way that
Psychiatrist/Psychologists evaluate the validity of a measurement method.

1. First, this process requires empirical evidence. A measurement method cannot be

declared valid or invalid before it has ever been used and the resulting scores have
been thoroughly analysed

2. Second, it is an ongoing process. The conclusion that a measurement method is valid

generally depends on the results of many studies done over a period of years

3. Third, validity is not an all-or-none property of a measurement method. It is possible

for a measurement method to judged "somewhat valid" or for one measure to be
considered "more valid" than another

Reference:

Statistics notes complied by Dr D, Raj kiran, Dept of Psychiatry, KIMS Narketpally

127
FUNCTIONAL
NEURO-
ANATOMY

128
 Frontal Lobe Syndromes

Dr Amitkumar Chougule

Background

The frontal lobe is the largest lobe in the brain. In any case, dysfunctions of the frontal
lobe can give rise to relatively specific clinical syndromes.

Traditional classification systems divide the frontal lobes into:

1. The precentral cortex

2. Prefrontal cortex
3. Orbitofrontal cortex
4. Superior mesial regions
Each of these areas has widespread connectivity.

Given the unique connectivity between the frontal regions and deeper brain
structures, lesions of these areas or their connections generate relatively distinctive
clinical behaviors.

Dorsolateral Frontal Cortex:

1. Dorsolateral frontal cortex is concerned with planning, strategy formation, and

executive function
2. Patients with dorsolateral frontal lesions tend to have apathy, personality
changes, abulia, and lack of ability to plan or to sequence actions or tasks.
3. These patients have poor working memory for:
➢ Verbal information (if the left hemisphere is predominantly affected)
➢ Spatial information (if the right hemisphere bears the lesion brunt)
The frontal operculum:

1. It contains the center for expression of language

2. Patients with left frontal operculum lesions may demonstrate Broca aphasia
and defective verb retrieval
3. Patients with exclusively right opercular lesions tend to develop expressive
aprosodia
The orbitofrontal cortex:

1. It is concerned with response inhibition

2. Patients with orbitofrontal lesions tend to have difficulty with disinhibition,
emotional lability, and memory disorders
3. Patients with such acquired sociopathy, or pseudopsychopathic disorder, are
said to have an orbital personality
4. Personality changes from orbital damage include impulsiveness, puerility, a
jocular attitude, sexual disinhibition, and complete lack of concern for others

Superior Mesial region:

129
 ➢ Patients with superior mesial lesions affecting the cingulate cortex typically
develop akinetic mutism
➢ Patients with inferior mesial (basal forebrain) lesions tend to manifest
anterograde and retrograde amnesia and confabulation
➢ Broca aphasia from a lesion in areas 44 and 45 on the left hemisphere leads
to nonfluent speech, agrammatism, paraphasias, anomia, and poor repetition
➢ Lesions anterior, superior, and deep to (but sparing) the Broca area produce
abnormal syntax and grammar but repetition and automatic language are
preserved. This disorder is known as transcortical motor aphasia and
uninhibited echolalia is common.
➢ Memory disturbances only develop with lesion extension into the septal
nucleus of the basal forebrain
➢ Appreciation of verbal humor is most impaired in right frontal polar pathology
Pathophysiology:

➢ The frontal lobe mediated responsibility of decision making depends on the valuation
of a choice, such as its costs, benefits, and probability of success, as well as the
assessment of the outcome of a given choice, in order to adapt future behaviors
appropriately
➢ The anterior cingulate cortex is primarily responsible for selecting choices and
evaluating the outcome of that selection to ensure adaptation to the environment
➢ The orbitofrontal cortex is responsible for changes in behavior in response to
unexpected outcomes
➢ Poor judgment and inappropriately weighting the value of past experiences may, as a
result, occur with frontal lobe dysfunction
➢ Working memory involves a complex circuit that involves many brain regions, including
the dorsolateral frontal cortex, thalamus, and parts of the temporal and parietal cortices
➢ Working memory is defined as memory for a limited amount of information (such as a
telephone number) that needs to be kept in consciousness for a few seconds (until the
number is dialed) and then may be lost forever
➢ Most patients are able to hold 6 or 7 digits in working memory. Patients with frontal
lobe impairment may have decreased capacity in working memory (eg, shortened digit
span) or difficulty manipulating information in working memory (eg, impaired reverse
digit span test)

Epidemiology:

Major causes of syndromes of frontal lobe dysfunction:

1. Degenerative Dementias Including Alzheimer Disease

2. Dementia With Lewy Bodies
3. Parkinson plus Syndromes
4. Frontotemporal Dementias
5. Cerebrovascular Disease
6. Normal Pressure Hydrocephalus And Other Hydrocephalic Disorders
7. Psychiatric Diseases such as schizophrenia and major depression

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In addition, any neurologic or psychiatric disease that can affect the frontal lobe (eg, multiple
sclerosis, CNS lupus) may be associated with frontal lobe dysfunction.

Frontal lobe dysfunction is associated with blood alcohol level and occurs during acute
intoxication with many recreational drugs.

Sex:

Traumatic brain injury is much more common in men than women both in the United States
and worldwide. Gender predominance depends on the specific underlying neurologic disorder.

Age:

➢ The relative likelihood of different causes of frontal lobe dysfunction is a function of

patient age.
➢ In teenagers and young adults, the most common causes are mental retardation,
traumatic brain injury, and drug intoxication.
➢ In middle aged patients, brain tumors, cerebrovascular disease, infections such as
HIV, multiple sclerosis, and early onset degenerative dementias are common.
➢ In late life, cerebrovascular disease and degenerative dementias are predominant
causes of frontal lobe dysfunction.
➢ The main degenerative dementias of frontal lobe predominance, frontotemporal lobar
degenerations, together with Alzheimer disease, are the most common degenerative
dementias in the presenile age (younger than 65 years).
PRESENTATION

Main behavioural disorders suggestive of dysexecutive syndrome

Highly suggestive:

1. Global hypoactivity with abulia-apathy-aspontaneity

2. Global hyperactivity with distractibility-impulsivity-disinhibition
3. Perseveration and stereotyped behaviour
4. Syndrome of environmental dependency (imitation and utilisation behaviour)
Other supportive features:

1. Confabulation and reduplicative paramnesia

2. Anosognosia and anosodiaphoria
3. Disturbances of emotion and social behaviour
4. Disorders of sexual behaviour and control of micturition
Main cognitive disorders suggestive of dysexecutive syndrome

Highly suggestive deficits:

1. Response initiation; response suppression and focused attention

2. Rule deduction; maintenance and shifting of set
3. Problem-solving and planning
4. Information generation
Supportive deficits and developing areas

1. Tasks coordination and divided attention

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 2. Sustained attention
3. Strategic mnemonic processes
4. Theory of mind
History:

The examiner should inquire about the following changes:

Appropriateness of behavior: Does the patient say things that he or she would never have
said before, such as "You are so fat" or "That is a really ugly dress"?

Patient's table manners: Does the patient now take food and start eating before everyone
else or take food from other people's plates without asking? Patient's empathy and ability to
infer the mental state of others: This kind of dysfunction often leads to inappropriate behavior.

Possible apathy: Does the patient care less about hobbies, family members, and finances
then previously? An increase or decrease in the patient's sexuality or in his or her judgment
about possible liaisons

Indeed, a detailed past psychiatric history is required

Many commonly used brief mental state tests, including the MiniMental State Examination,
are not designed to test frontal lobe function—they are insensitive and not specific to frontal
lobe dysfunction.

Two validated bedside tools that extend the cognitive screen to the frontal lobes are the

1. Frontal Assessment Battery(FAB)

2. Montreal Cognitive Assessment (MoCA)

Tests relatively sensitive to frontal lobe dysfunction include the following:

1. Go/NoGo task:

2. Antisaccade task:

➢ After checking eye movements and visual fields, ask the patient to move his or her
eyes contralateral to the stimulus (usually wiggling finger).
➢ A failure in the task (visual grasp) may reflect dysfunction in the dorsolateral prefrontal
cortex or a lesion interrupting the pathway between this frontal region and the superior
colliculus (Munoz and Everling, 2004)
3.Trail making test (TMT):

➢ This test is widely used as a diagnostic tool for eliciting shifts between cognitive sets.
➢ TMT requires cognitive flexibility generated through activity in the dorsolateral and
medial prefrontal cortices.
4. Lexical fluency (word generation, Thurstone test):

➢ Ask the patient to generate as many words as possible beginning with the letter F in 1
minute
➢ No proper names or derivatives are allowed

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 ➢ A normal score for a native English speaker with at least a high school education is at
least 8 words
➢ Note that semantic category fluency tasks (eg, naming as many animals or fruits in a
minute as possible) localize to the temporal not frontal lobes. Therefore, such tests are
not as useful as the letter fluency task for testing frontal dysfunction.
5. Design fluency:

➢ (How many designs with 4 lines) has been suggested as an alternative for aphasic
patients
➢ Although the lexical fluency test has relatively poor localizing value, marked
impairment is lateralizing to the left frontal lobe
6. Attention and concentration test:

➢ Serial 7 s (ie, serial subtraction of 7 from 100 to 65) has been proposed as a measure
of attention and concentration
➢ Spelling the word world backwards is commonly used as a substitute for patients who
cannot perform the serial 7s
➢ Digit span is also used to measure attention and concentration. A normal span is 6-7
digits forward and 4-5 backward

7. Alternating sequences task:

➢ Ask the patient to copy a segment with alternating M s and N s. Perseveration may
occur in patients with frontal lobe lesions
8. Luria's 3step motor program:

➢ It is a sequential performance of 3 movements, usually the fist edge–palm test, which

is making a fist, laying the hand on edge, and laying the palm of the hand down on the
table
➢ Consider perseveration or failure to perform sequential movements an abnormal
response
9. The applause test:

➢ It is also manifestation of perseveration

➢ Patients are asked to clap 3 times after demonstration by the examiner
➢ Abnormal outcome consists of clapping 4 or more times (positive applause sign). This
test has been felt highly specific for parkinsonian disorders with frontal involvement.
General bedside and neuropsychological testing for these deficits is described below.

1. Aphasia:

➢ Aphasia may result from lesions in and around the Broca area
➢ Classic Broca type aphasia consists of nonfluent speech, grammatical errors, inability
to repeat and to name objects and verbs, and deep dyslexia
➢ Aphasia can be assessed at the bedside by asking patients to name and repeat both
common and low frequency words (eg, pen and watch are considered easy, but clip,
lens, and hammock are considered difficult)
➢ "No ifs, ands, or buts" is commonly applied. Assess reading, writing, and spontaneous
speech. Deep dyslexia and spelling disorders are extremely common in patients with
Broca aphasia.

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2. Apraxia:

➢ Patients with frontal lesions can be apraxic for skilled limb movements without losing
the knowledge or understanding of the movement. Patients can also be apraxic
because of supplementary motor area lesions and convexity lesions, in addition to
parietal lesions.
➢ Asking the patient to pantomime the use of real tools (eg, scissors, bread knife,
hammer, screwdriver) can test praxis.
3. Neglect:

➢ Neglect is most common after lesions of the right hemisphere involving either the right
parietal lobe or the right frontal lobe
➢ Other areas, including the thalamus and the basal ganglia, may also be implicated.
Patients with right brain lesions typically neglect the left hemispace
➢ Neglect can be further fractionated into motor and sensory components, extinction,
anosognosia (denial of illness), and anosodiaphoria (minimization of illness)
➢ Neglect can be tested at the bedside by asking the patient to draw or read
➢ Patients may neglect the left half of the drawing or leave off the left half of words
(neglect dyslexia)
➢ Cancellation tasks require that the patient cancel or cross out all the letter A s, circles,
or some other element mixed with others on a page
➢ Patients with neglect may omit cancelling the targets on the left half of the page
➢ Line bisection tests require the patient bisect a line of sufficient length (usually 12
inches or more). Patients with neglect may bisect significantly to the right of midline.
4. Constructional apraxia:

➢ This refers to the inability to draw.

➢ On the Mini Mental State Examination, subjects are asked to draw interlocking
pentagons
➢ Complex figures can be taken from the Wechsler Adult Intelligence Scale (WAIS) or
the Rey Complex Figure Test
➢ Constructional apraxia localizes to the right hemisphere or to the frontal lobes.
5. Judgment, insight, and social appropriateness:

No good tests exist for these functions other than observation. Patients can score highly on
the WAIS or other cognitive tests and still be unable to behave appropriately.

6. Acquired sociopathy can occur with individuals with orbitofrontal cortex injuries who may
score highly on all cognitive measures and yet are unable to hold a job, make and maintain
long term personal relationships, and exercise judgment.

7. Memory deficits: Patients with frontal lobe injuries, especially orbitofrontal injuries, may
have deficits of declarative memory or memory for temporal order of events.

8. Lack of originality, inattentiveness, and inappropriate emotional reactions: Some

patients with traumatic lesions of the frontal lobes have these qualities. Patients cannot plan,
initiate, organize, or form and maintain personal relationships. They lack insight and remain
dependent on caregivers despite normal intellect, as measured conventionally.

9. Frontal release responses:

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 ➢ Frontal release responses, including suck, grasp, snout, and groping reflexes, may be
present, as may paratonic rigidity and abnormal gaze
➢ Although these are not cognitive signs of dysfunction, they certainly help in localization
and diagnosis
10. Utilization behavior:

➢ This behavior includes using, touching, or playing with an object that most people
would consider inappropriate and may be a sign of frontal lobe dysfunction
➢ An example would be a patient taking a physician’s stethoscope off his desk and
listening to his heart while the physician is sitting and talking with him.
11. Alien hand syndrome:

➢ This occurs when a patient’s hand assumes complex positions that are not under the
patient’s volitional control and may also be a sign of frontal systems dysfunction.
12. Gait impairment:

➢ A relatively upright posture in the setting of short stride, hesitant, slightly widened base
gait are characteristic of frontal lobe disorders. Some patients, even when helped to
stand up, cannot begin walking (ignition apraxia)
➢ Others have poor balance with risk of falling from the slightest shove or surface
irregularity. Frontal gait is common in advanced Alzheimer disease, some vascular
dementias, and normal pressure hydrocephalus.
13. Incontinence:

➢ Dysfunction of the posterior superior frontal gyri and anterior parts of the cingulate
gyrus can lead to incontinence of urine and stool
➢ Patients frequently have no warning of the need to urinate or defecate, and are
surprised and embarrassed when they find they have soiled themselves

TREATMENT

Medical Care:

➢ Medical care depends entirely on the pathology present

➢ Physical and occupational therapy remain an important cornerstone of motor symptom
management in FTD
➢ Speech therapy may also help patients manage symptoms associated with aphasia,
apraxia, and dysarthria
➢ Recent advances in the understanding of FTLD pathophysiology and genetics have
led to development of potentially disease modifying therapies, as well as symptomatic
therapies aimed at ameliorating social and behavioral deficits.
Consultations:

➢ Consultation with a neuropsychologist and/or behavioral neurologist is indicated to

determine the nature and extent of the cognitive deficits present and to help work with
the patients and families
Consultation with a social worker may also be helpful. Activity Patients with frontal lesions
and deficits frequently need supervision because of their lack of impulse control and their
inability to form and follow plans and strategy.

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 Basal Ganglia

Introduction:

The basal ganglia are a collection of masses of grey matter situated within each cerebral
hemisphere. Basal ganglia/ Basal nuclei are grouped together based on their interconnections. Basal
ganglia form the important component of the extrapyramidal motor system.

Major Structures:

The basal ganglia are generally considered to include:

1. Caudate nucleus

2. Putamen

3. Globus pallidus (paleostriatum or pallidum)

4. Subthalamic nucleus

5. Substantia nigra

6. Amygdala

7. Ventral striatum

8. Ventral pallidum

The commonly used terms:

1. Striatum refers to the caudate nucleus and the putamen together

2. Corpus striatum refers to the caudate nucleus, the putamen, and the globus pallidus

3. Lentiform nucleus refers to the putamen and the globus pallidus

4. The ventral striatum includes the nucleus accumbens and the olfactory tubercle

5. The ventral pallidum is a region of group of neurons termed the substantia innominata

Amygdala is included within basal ganglia as it occupies an important position and connection
between the basal ganglia and the limbic system. Embryological evidence supports inclusion of the
amygdala as a basal ganglia structure.

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137
INPUTS TO THE BASAL GANGLIA.

The striatum is the major recipient of the inputs to the basal ganglia. Three major afferent systems
are known to terminate in the striatum:

1. Corticostriatal

2. Nigrostriatal

3. Thalamostriatal

Corticostriatal:

➢ The corticostriatal projection originates from all regions of the neocortex, arising primarily
from the pyramidal cells of layers V and VI, which use the excitatory neurotransmitter
glutamate.

➢ Afferents from the sensorimotor cortex terminate predominantly in the putamen;

association regions of the cortex terminate preferentially in the caudate nucleus.

➢ The prefrontal regions, in particular, provide a heavy input to the head of the caudate
nucleus. In addition, afferents from the limbic cortical areas, the hippocampus, and the
amygdala terminate in the ventral striatum.

Nigrostriatal pathway

➢ The second major class of afferents uses the neurotransmitter dopamine.

➢ Electron microscopy studies have shown that many of the synapses formed by dopamine
axon terminals on medium spiny neuron dendrites are immediately adjacent to the synapses
provided by corticostriatal axons, suggesting that dopamine may play an important role in
modulating the excitatory influence of cortical projections on striatal neurons.

Thalamocortical:

➢ The thalamic nuclei providing the projections are the intralaminar nuclei, particularly the
central median nucleus.

INTERNAL PROCESSING:

The striatum receives a major projection from the cerebral cortex.

Direct Pathway:

➢ Within the striatum, the subclass of medium spiny neurons that contain the neuropeptide
substance P sends inhibitory projections to the internal segment of the globus pallidus in
what is termed the direct pathway.

➢ The direct loop projections from the striatum to GPi inhibit the inhibitory pallidothalamic
pathway and result in net cortical excitation and facilitation.

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Indirect pathway:

➢ In contrast, the subpopulation of medium spiny neurons that contain the neuropeptide
enkephalin provides inhibitory projections to the external segment of the globus pallidus,
which sends inhibitory afferents to the internal segment of the globus pallidus in what is
termed the indirect pathway.

➢ The STN facilitates the inhibitory projection of the GPi to the thalamus resulting in a net
decrease in activity in the thalamocortical pathways

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OUTPUT OF BASAL GANGLIA:

➢ The internal segment of the globus pallidus is the source of much of the output of the basal
ganglia.

➢ Segment of the globus pallidus provides a projection to the ventral lateral and ventral
anterior nuclei of the thalamus and to the intralaminar thalamic nuclei, particularly the
central median nucleus.

➢ The pars reticulata of the substantia nigra also provides a projection to the ventral anterior
and ventral lateral thalamic nuclei. These portions of the ventral lateral and ventral anterior
thalamic nuclei project to the premotor and prefrontal cortices.

➢ As a result of the projections of the premotor and prefrontal cortices to the primary motor
cortex, the basal ganglia are able to influence indirectly the output of the primary motor
cortex.

➢ In addition, the cortical output of the basal ganglia exhibits marked convergence; although
the striatum receives afferents from all regions of the neocortex, the eventual output of the
globus pallidus and pars reticulata is largely conveyed through the thalamus to a much
smaller portion of the neocortex —the premotor and prefrontal regions.

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141
142
Functions and the functional circuitry of basal ganglia:

1. Regulation of voluntary movement

2. Learning of motor skills

3. Execution of a particular movement

4. Preparation of the body for the movement

5. Role in cognition, emotion, and oculomotor control

6. Behavior,memory, attention, and reward processes

7. Learning of associations between stimuli, actions and rewards

8. Selection between competing response alternatives

9. Motivational modulation of motor behavior

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Cognitive loop:

Frontal lobe

Thalamus caudate

Globus
pallidus

Limbic loop:

The limbic loop may be involved in the motor expressions of emotion

Oculomotor loop:

• The oculomotor loop is involved in the control of saccadic eye movements

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Recent advances:

➢ Hyperdirect pathway:

• More recently a third basal ganglia pathway has been described called the “hyperdirect
pathway”

(Nambu et al., 2002; Nambu, 2004)

• This pathway avoids the striatum and consists of connections between motor cortex, STN,
and GPi

• The purpose of this pathway is to inhibit actions that have already been initiated

• Disturbance of this pathway plays a role in impulsive behaviors

➢ Historically, motor systems have been divided into pyramidal (corticospinal) and
extrapyramidal (basal ganglia) components. However, this division is no longer accurate for
several reasons. First, other structures of the brain outside the traditional pyramidal and
extrapyramidal systems, such as the cerebellum, are involved in the control of movement.
Second, the pyramidal and extrapyramidal systems are not independent; the neural circuits
of these systems are interconnected. For example, the basal ganglia influence motor
behavior through certain regions of the cerebral cortex, which then directly (through the
corticospinal tract) or indirectly (through specific brainstem nuclei) produce motor activity.

➢ More recent studies of the connections of the basal ganglia support a role for these
structures in cognitive functions. The DLPFC has been shown to receive inputs from portions
of the thalamus that are the targets of projections from specific locations within the internal
segment of the globus pallidus, providing evidence for a distinct pallidothalamocortical
pathway.

➢ In addition to linking association regions of the cerebral cortex, such as the prefrontal and
posterior parietal areas, with the control of motor activity in the primary motor cortex, some
of the output of the basal ganglia seems to be directed back to regions of the prefrontal

145
 cortex. These findings suggest that “closed” loops are present between the prefrontal cortex
and basal ganglia, which presumably have a cognitive rather than a motor function.

THE ROLE OF THE BASAL GANGLIA IN PSYCHIATRIC DISORDERS:

1. OCD

2. Autism

3. ADHD

4. Schizophrenia

5. Depression

6. Addiction

OCD Spectrum disorders:

• There is evidence of basal ganglia dysfunction from imaging studies of OCD

• Both reduced and increased volumes of caudate nuclei are reported

• Increased caudate metabolism has been found to reduce after effective treatment of the
OCD

• Patients with OCD have shown increased caudate blood flow

• Imagining studies point to the importance of limbic-orbitofrontal-basal ganglia-

thalamocortical circuits in the pathogenesis of OCD

• Obsessive-compulsive symptoms may occur when an aberrant positive feedback loop

develops in the excitatory fronto-thalamic neuronal circuit

• OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits due to an

imbalance of tone between direct and indirect striato-pallidal pathways

• The basal ganglia serve as

➢ motor pattern generators in the brainstem

➢ cognitive pattern generators in the cerebral cortex

• The loop neocortex - basal ganglia -thalamus -neocortex plays a role in establishing

➢ cognitive habits

➢ motor habits

• Thus cortical-basal ganglia loop dysfunction in OCD reflects

➢ repetitive actions (compulsions)

➢ repetitive thoughts (obsessions)

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AUTISM:

• Significant enlargement of the total caudate volume in the order of 8% was found in the
subjects with autism

• This greater caudate volume was proportional to the increased total brain volume

• Motor, social, and communicative impairments in boys with autism are associated with
shape abnormalities in the basal ganglia

• Studies suggest abnormalities within frontal-subcortical circuits

• Glutamate dysfunction in the basal ganglia may be associated with Autism

ADHD:

• This condition linked clinically and genetically to GTS and OCD

• There is evidence from Neuroimaging studies of striatal dysfunction in patients with ADHD

• Teicher and colleagues concluded that ADHD may be related to functional abnormalities in
the putamen

• Boys with ADHD showed significantly smaller basal ganglia volumes compared with typically
developing boys

• They concluded that in ADHD there is atypical brain development involving multiple frontal-
subcortical control loops

SCHIZOPHRENIA:

• Basal ganglia disturbance has a role in causation of Schizophrenia

• In the striatum anomalies of dopamine synthesis, storage and release have been reported

• Striatal dopaminergic system is overactive

• The striatum of schizophrenia patients displays augmentation of presynaptic dopamine

function indicating an increase in dopamine synthesis capacity

• Schizophrenia subjects show elevations in striatal D2 receptors

• Enhanced striatal dopamine levels, synthesis and release are present in drug free
schizophrenia subjects

• In first degree relatives of schizophrenia subjects

➢ Striatal dopamine synthesis is higher

➢ Abnormalities in D2 receptors are present

• Elevated striatal dopamine function is correlated with:

1. Prodromal psychotic symptoms in schizophrenia

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 2. Predictor of the psychotic episode

3. Risk factor for the disease

• In the substantia nigra following abnormalities are reported in patients with schizophrenia

➢ High variability of tyrosine hydroxylase (TH) levels

➢ Increase in homovanillic acid

➢ Increase in glutamate receptor subunits

• Mesolimbic dopamine system and the D3 receptor have been implicated in schizophrenia

• D3 mRNA positive neurons are highly concentrated in the ventral striatum

• D3 receptors are also present in large numbers in the limbic striatal-pallidal thalamic loop

• Joyce and Gurevich have shown that there is 45% increase in D3 receptor numbers in ventral
striatal neurons and their striatopallidal targets in patients with schizophrenia

• This increase in D3 receptors is reduced by antipsychotic treatment

• The atypical antipsychotic drugs with its 5HT2 antagonist action are very effective in
schizophrenia

• This finding has focused attention on the interactions within the striatum between
dopamine and serotonin systems

• There is evidence reviewed by Kapur and Remington that blockade of nigral 5HT2 receptors
can lead to disinhibition of striatal dopamine release

• These mechanisms are likely to be the focus of future therapeutic drug development
programmes in schizophrenia

DEPRESSION:

• Two interrelated basal ganglia thalamocortical circuits have a role in pathophysiology of

Depression

1. These are the limbic circuit connecting the amygdala and anterior cingulate with the
ventral striatum and medial and ventral lateral prefrontal cortex

2. Prefrontal circuit connecting the basal ganglia particularly the head of the caudate
and the lateral prefrontal cortex

• Functional imaging studies have suggested pathological interactions between the amygdala-
ventral striatum and prefrontal cortex in the genesis of major depression

• There is positive correlations between regional cerebral blood flow, glucose metabolism in
amygdala and depression severity ratings

• During antidepressant treatment amygdala metabolism decreases towards normal

• Depressed patients performing a complex planning task fail to demonstrate the normal
control finding of increased caudate activation with increasing task difficulty

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 • Animal studies have shown an association between nucleus accumbens and motivation

• Study in humans suggested that the nucleus accumbens important focus in patients with
affective disorders

• Dopamine system has a role in depression

1. Similarities between psychomotor retardation in depression and the bradykinesia of PD

2. Increased incidence of depression in PD

• Laasonen-Balk et al considered the hypothesis that:

1. Depression is associated with a net decrease in dopamine transmission

2. Secondary or compensatory up regulation of D2 receptor density

• Late onset depression:

➢ MRI studies have reported increased incidence of caudate hyperintensities in elderly

depressed patients

➢ The presence of subcortical hyperintensities may be associated with poor prognosis

➢ Cerebrovascular insufficiency in subcortical and basal ganglia structures may precipitate

some cases of late onset affective disturbance

ADDICTION:

• It has been hypothesised that the amygdala is a critical structure in which neuroadaptations
lead to positive effects of many drugs of misuse

• Amygdala has a role in abstinence or withdrawal of the drugs of misuse

• The nucleus accumbens has been described as a limbic-motor interface and receives
innervation from amygdala

• Connections of the orbitofrontal cortex-ventral tegmental area-nucleus accumbens-

thalamus are important for drug reinforcement and addiction

• This circuit is important in the compulsive aspect of drug taking behaviour

ROLE OF BASAL GANGLIA IN NEUROPSYCHIATRIC DISORDERS:

1. Parkinson’s disease

2. Huntington’s disease

3. Progressive supranuclear palsy(PSP)

4. Wilson’s disease (WD)

5. Fahr’s disease

6. Gilles de la Tourette’s syndrome (GTS)

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PARKINSONS DISEASE:

Pathologically PD is characterized by

• Degeneration of the dopamine neurons in the substantia nigra pars compacta accompanied
by a loss of dopamine terminals in the striatum

• Presence of Lewy bodies in the substantia nigra, locus coeruleus, nucleus basalis, raphe and
ventral tegmental area

• The SNc cells are the origin of the nigrostriatal dopaminergic pathway

• Loss of dopamine input to the striatum decreases thalamocortical activation by effects

mediated by both D1 and D2 receptors

• There is decreased activity in the direct loop mediated by the D1 receptor causing loss of
striatal inhibition of GPi and increased inhibition of the motor thalamus resulting in
decreased cortical activation

• There is also decreased inhibition of the indirect loop mediated by the D2 receptor

• The STN is released from the inhibitory control of GPe which causes increased activity of the
STN which increases the inhibitory effects of GPi

• Both of these effects decrease the thalamic drive to the motor cortex causing hypokinesia
and bradykinesia

HUNTINGTONS DISEASE:

• In Huntington disease (HD) there is loss of ENKergic neurons in the striatum which project
primarily to Gpe

• Loss of these neurons removes inhibition from GPe which leads to inhibition of STN

• Excitation of thalamus leading to increased thalamocortical activity and hyperkinesis

• Depression is a very common in HD with a frequency of up to 40% of cases

• Postulated to dysfunction of limbic-caudate and frontocaudate circuitry

• PET data have demonstrated that depression in HD is associated with orbitofrontal and
inferior prefrontal hypometabolism

• Cognitive impairment is present early in the course of the disease

• Pattern of deficits is suggestive of frontosubcortical dementia

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Progressive supranuclear palsy: (Steele-Richardson-Olszweski’s disease):

Pathologically PSP is considered a “tauopathy” and the main neurochemical deficits found relate to
dopamine in the nigrostriatal pathway and acetylcholine

• Cognitive impairment is very common in PSP affecting 80% of patients

• The pattern of deficits is characteristic of “subcortical dementia”

Wilson’s disease (WD)/ hepatolenticular degeneration:

• Autosomal recessive disorder of copper metabolism

• The cerebral pathology of WD mainly affects the lenticular nuclei (pallidus and putamen)

• Abnormalities can also be found in the caudate, thalamus, cerebellar nuclei and white
matter

Fahr’s disease (idiopathic clacification of the basal ganglia):

• Characterised by progressive calcium deposition in the basal ganglia

• Tissue damage by free radicals or by abnormal iron transport triggers calcification

• The pallidus is most affected

• The pattern of cognitive impairment found in FD is of the frontosubcortical type

Gilles de la Tourette’s syndrome (GTS) (Tourette’s disorder):

• Characterized by a combination of both multiple motor and one or more vocal (phonic) tics
which wax and wane and occur many times a day in bouts with varying intensity and
complexity

• Its onset occurs before the age of 18 years

• There is evidence of involvement of the dopaminergic system

• Caudate nucleus volumes were significantly smaller in children and adults with GTS

• Lenticular nucleus volumes were smaller in adults with GTS and in children with GTS with
comorbid OCD

• Smaller lenticular nucleus volumes serves as additional marker for the presence of comorbid
OCD and for the persistence of tic symptoms into adulthood

References:

1. H A Ring, J Serra-Mestres. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg

Psychiatry 2002;72:12–21

2. Darlene Susan Melchitzky, M.S., and David A. Lewis, M.D. Functional Neuroanatomy. In
Benjamin James Sadock, Virginia Alcott Sadock, Pedro Ruiz, Editor. Comprehensive textbook
of Psychiatry. 10th ed. Wolters Kluwer;2017. P. 125-29

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 Discuss the functional anatomy of hypothalamus, its Dysfunctions in
psychiatric disorder

General:
• Small structure that is a part of the diencephalon and sited at the lower part of the lateral
wall and floor of the third ventricle
• Located below the thalamus and weighs about 4 grams
• Separated macroscopically from the thalamus by the hypothalamic sulcus and lies in front of
the interpeduncular nuclei
• There are prominent neural connections (portal hypophyseal vessels) with the posterior lobe
of the pituitary (hypothalamohypophyseal tract) and vascular connections with the anterior
lobe i.e. hypothalamic control of the pituitary
• Functionally part of the limbic system

Hypothalamic Relations:
1. Superior: Hypothalamic sulcus
2. Inferior: Optic chiasm, tuber cinereum, mammilary bodies, median eminence and infundibulum
3. Anterior: Lamina terminalis
4. Posterior: Midbrain tegmentum
5. Medial: 3rd ventricle
6. Lateral: Internal capsule

Hypothalamic Nuclei:
1. Anterior: supraoptic, preoptic, suprachiasmatic, paraventricular
2. Middle (tuberal): infundibular, lateral, dorsal, dorso and ventromedial, posterior
3. Posterior: Mammilary, posterior

Regions:
1. Mammillary region (includes mammillary bodies).
2. Tuberal region (tuber cinereum, and infundibulum).
3. Supraoptic region (superior to optic chiasm).
4. Preoptic region.

Afferent and Efferent Hypothalamic Connections:

1. Connections with limbic system, nuclei of the midbrain tegmentum, thalamus, lenticular nucleus,
mammillary nuclei, reticular parts of midbrain.
2. Tracts: Medial forebrain bundle, fornix, stria terminalis, mammillary peduncle, rhinohypothalamic
fibres, etc.

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Important Hypothalamic Regulatory Functions: Homeostasis
1. Temperature regulation (thermoregulation)
2. Neuroendocrine hormonal control of: Catecholamines, vasopressin, oxytocin, TSH, ACTH,
FSH, LH, prolactin, GH (by releasing and inhibiting hormones RH/IH) ie regulation of
hormonal release from the pituitary gland (hypophysis) ie control of the pituitary gland
3. Appetite control (thirst, hunger) ie eating and drinking (satiety and feeding center)
4. Sexual behaviour, blood circulation
5. Defense reactions (fear, rage); sleep wake cycle, aggression, pleasure, defense
mechanisms ie regulator of emotional and behavioural patterns.
6. Anterior hypothalamus: regulates parasympathetic functions.
7. Posterior hypothalamus: regulates sympathetic functions.
8. Supraoptic and paraventricular nuclei are the principle producers of oxytocin and

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vasopressin (ADH).
9. Regulation of diurnal rhythms and states of consciousness - especially the suprachiasmatic
nucleus that establishes patterns of sleep.

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155
156
 Limbic circuit, give an account of its lesions/ Neuro anatomy of Limbic
system with appropriate diagrams/ Describe the limbic circuit

Limbic system:

➢ The term ‘limbic system’ was first used by MacLean in 1952 to describe a set of
structurally and functionally related structures of the brain bordering the midline, inner
surface of each cerebral hemisphere
➢ The LIMBIC SYSTEM includes diverse cortical and subcortical structures located mainly in
the medial and ventral regions of the cerebral hemispheres
➢ These structures are unified by their evolutionarily ancient origins, and they constitute
the major portion of the forebrain in many species
➢ Only in higher mammals has the larger neocortical mantle surpassed the limbic system in
size
➢ A group of structures that lie in the border zone between cerebral cortex
(telencephalon) and hypothalamus (diencephalon)
➢ Includes parts of cerebrum, diencephalon, midbrain
➢ Earlier known as the rhinencephalon- smell brain
➢ Anatomically, the limbic structures include the:
i. Subcallosal
ii. The cingulate
iii. The parahippocampal gyri
iv. The hippocampal formation
v. The amygdalaoid nucleus
vi. The mammillary bodies
vii. The anterior thalamic nucleus
➢ Functionally, promote a bridge between hypothalamus and neocortex that is endocrine,
visceral, emotional and voluntary responses to the environment
➢ Therefore, it plays an important role in emotion, behavior, drive and memory

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The main circuit of limbic system

158
Limbic Lobe vs Limbic system:

Limbic Lobe

Limbic lobe Limbic system

(Cortical areas of the limbic system) (Limbic lobe+ Nuclei +connection)
1. Parahippocampal Nuclei:
gyrus 1. Amagdyla
2. Hippocampus 2. Septal nuclei
3. Orbitalfrontal 3. Mammillary body
4. Cingulate gyrus 4. Anterior thalamus
5. Insula Connection:
1. Fornix
2. Median forebrain bundle
3. Stria-terminalis
4. Mamillo-thalamic tract

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 Hippocampal formation includes hippocampus, dentate gyrus, Subicular complex, gyrus
fasciolaris & indusium griseum

Hippocampus:

➢ Curved elevation of grey matter extends the entire length of the floor of the inferior horn of
the lateral ventricle
➢ Resembles a seahorse in coronal section and is called Ammon’s horn / ram’s horn /cornua
ammonis
➢ Three major parts- subiculum, hippocampus proper, dentate gyrus
➢ Anterior expanded end has shallow grooves- pes hippocampus
➢ Terminates posteriorly below splenium of corpus callosum
➢ Ventricular surface is covered with ependyma
➢ Histologically- 3 layers:
• Superficial molecular layer
• Middle pyramidal layer
• Inner polymorphic layer
➢ Axons of the pyramidal layer form a thin layer of white matter beneath the ventricular
ependyma- alveus

Connections of hippocampus:

Afferent:

➢ Cingulate gyrus
➢ Septal nuclei via fornix
➢ From the hippocampus of the oppposite side via commissure of fornix
➢ fibers from indusium griseum pass posteriorly via longitudinal striae
➢ Entorhinal area
➢ Dentate and parahippocampal gyri

Efferent:

➢ Axons of pyramidal cells of hippocampus ----Alveus ----Fimbria----crus of

➢ fornix------Body of fornix-----two columns of fornix.
➢ The columns of fornix at the region of interventricular foramen ends as precommissural and
postcommissural fibers.

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Precommissural fibers end in septal nuclei, lateral preoptic area, anterior part of hypothalamus.
They also go to habenular nuclei via stria medullaris thalami.

Postcommissural fibers end in mamillary bodies, anterior nuclei of thalamus and tegmentum of
midbrain.

Dentate gyrus

• Lies between the fimbria of the hippocampus and the parahippocampal gyrus.
• Anteriorly it is continued into the uncus
• Posteriorly it is continuous with the indusium griseum
• Histologically it has 3 layers
o Superficial molecular layer
o Middle granular layer
o Inner polymorphic layer

Indusium griseum

• Is a thin layer of grey matter that covers the superior surface of the corpus callosum
• Medial and lateral longitudinal stria are embedded in it.
Parahippocampal gyrus

Lies betweenthe hippocampal fissure and the collateral sulcus.

Amygdaloid nucleus

• Situated in the uncus

• Lies anterosuperior to the tip of the inferior horn of the lateral ventricle

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 • Anteriorly related to the tail of the caudate nucleus
• Posteriorly, stria terminalis emerges
Connections of amygdaloid nucleus

➢ Afferent
➢ Neocortex
➢ Efferent
➢ Stria terminalis arises from the amygdaloid nucleus, follows the curve of the lateral ventricle
and ends in septal nuclei, hypothalamus, anterior perforated substance and piriform lobe
➢ Amygdala of two sides are interconnected by fibers passing through the stria terminalis of
one side crossing over to the opposite side through anterior commissure
➢ On reaching the interventricular foramen, fibers leave stria terminalis to enter the stria
medullaris thalami and reach habenular nucleus

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Mammillary bodies

• 2 small bodies situated adjacent each other behind tuber cinereum

• Part of hypothalamus
• Consists of a layer of white matter outside and a mass of grey matter inside.
• The grey matter consists a medial and a lateral nucleus
• Efferents reach anterior nucleus of thalamus through mammillothalamic tract
The limbic system is arranged as 3 concentric rings:

From a phylogenetic and cytoarchitectural view point, limbic lobe consists of:

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 1. Archicortex- (hippocampal formation and dentate gyrus)
2. Paleocortex- (piriform cortex of parahippocampal gyrus)
3. Mesocortex /juxtallocortex- transition between allocortex and neocortex (cingulate
gyrus)

Functions of Limbic System:

The functions of the limbic system are also ancient, and they play an important role for survival in
the animal kingdom
Limbic functions can be divided into the following four basic categories:

1. Homeostatic functions including autonomic and neuroendocrine control

2. Olfaction
3. Memory
4. Emotions and drive
Other important functions of limbic system:

1. Generates emotions (Emotional brain)

2. Add feeling to sensory experience which direct to behavior.

3. Affect: interpret the sensory experience as pleasant or unpleasant.

4. Memory and learning which is closely linked to emotion.

5. Sexual behavior, emotions of rage, fear, anxiety and motivation

Clinical implications:

TEMPORAL LOBE EPILEPSY:

➢ Form of focal epilepsy, a chronic neurological condition, Characterized by Recurrent

epileptic seizures arising from one or both temporal lobes
➢ Two main types
1. Mesial temporal lobe epilepsy (MTLE)
2. Lateral temporal lobe epilepsy (LTLE)
➢ Mesial temporal sclerosis:
1. 47-70% of all TLE
2. Severe neuronal loss in CA1, May spread to involve CA3 and CA4
3. CA2 and dentate are only mildly involved
4. Pathological abnormalities: -
1. Specific pattern of hippocampal neuron cell loss (m/c)
2. Associated with hippocampal atrophy and gliosis
3. Dispersion of granule cell layer in dentate gyrus
➢ Pts classically describe fear, déjà vu, jamaisvu, elementary and complex visual
hallucinations, illusions, forced thinking, emotional distress
2. Limbic Encephalitis:

➢ Limbic encephalitis is a form of encephalitis

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 ➢ An inflammatory process involving the hippocampi, amygdala and less frequently
frontobasal and insular regions of the limbic system and other parts of the brain
➢ Clinical features: -
i. Severe impairment of short-term memory (cardinal sign)
ii. Confusion
iii. Psychiatric symptoms (changes in behavior & mood – irritability,
depressive, sleep disturbances),
iv. Seizures
➢ 60% of the time, limbic encephalitis is paraneoplastic in origin
➢ Paraneoplastic limbic encephalitis (PLE) is a particularly severe form of limbic
encephalitis caused by neoplasms most commonly associated with small cell lung
carcinoma
➢ Whereas the majority of encephalities are viral in nature, PLE is often associated with
cancer
3. Alzheimer’s disease:

➢ Neurodegenerative changes in limbic system

➢ Amyloid proteins build up and form amyloid plaques (outside cells)
➢ Neurofibrillary tangles (inside cells), leads to neuronal death
➢ Hippocampus is one of first areas to degenerate, leads to anterograde amnesia
➢ Cortex also degenerates early, leads to retrograde amnesia and dementia

4. Kluver- Bucy Syndrome:

➢ Neurobehavioural syndrome associated with bilateral lesions in the medial temporal
lobe, particularly amygdala
➢ Clinical features
1. Facial Blunting (may not respond appropriately to stimuli)
2. Hyperphagia (extreme weight gain without a strictly monitored diet)
3. Hyperorality (marked tendency to examine all objects orally)
4. Hypermetamorphosis (an irresistible impulse to attend & react to visual stimuli)
5. Inappropriate Sexual Behavior (Hyper sexuality)
6. Atypical sexual behavior, mounting inanimate objects.
7. Visual Agnosia/ "psychic blindness" (inability to visually recognize objects)

5. Korsakoff’s syndrome:

➢ Amnestic syndrome, caused by thiamine deficiency

➢ Associated with poor nutritional habits of people with chronic alcohol abuse, gastric
carcinoma, haemodialysis etc.
➢ Leads to damage to:
1. Mammillary bodies
2. Dorsomedial nucleus of thalamus

➢ Symptoms:

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 Amnesia, confabulation, attention deficit, disorientation, and vision impairment , change
in personality like -lack of initiatives, spontaneity, lack of interest or concern, Executive
function deficits
➢ Recent memory more affected than remote, Immediate recall is usually preserved

6. Limbic system and schizophrenia:

➢ Ventricular enlargement

➢ Reduced limbic volumes

➢ Decreased size of hippocampus & thalamic

➢ Decreased amygdala response during facial recognition tasks (fMRI)

➢ Decreased activity in dorsolateral prefrontal cortex (PET)

➢ The Papez circuit is probably involved in schizophrenia:

1. The distortion of cortical neuronal organization of layer II of the ERC

2. Decreased size of hippocampus

3. Reduced number of GABAergic cells in the cingulate and anterior thalamus with
resultant glutamatergic excitotoxicity

7. Limbic system and Bipolar Disorder:

➢ Reductions in volume of the:

1. Frontal lobes

2. Basal ganglia

3. Amygdala

4. Hippocampus

➢ Functional studies have revealed decreased activity in the prefrontal cortex and anterior
cingulate gyrus, which is the centre for integration of attentional and emotional output
and helps effortful control of emotional arousal.
8. Limbic system and anxiety disorders:

➢ May be the result of a failure of the anterior cingulate and hippocampus to modulate the
activity of the amygdala (top-down regulation)
➢ A fear circuitry, involving the amygdala, prefrontal and anterior cingulate has been
described (bottoms-up regulation)
➢ The limbic system, which is involved in storing memories and creating emotions, is also
thought to play a central role in processing all anxiety-related information.

➢ People with obsessive-compulsive disorder (OCD) often show increased activity in the
basal nuclei, in particular the striatum and other frontal lobe areas of the forebrain

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9. ADHD

➢ Disrupted connections between the amygdala and orbitofrontal cortex may contribute to
behavioral disinhibition seen in individuals with ADHD

10. OCD

➢ Neuro-imaging has implicated the cortical-striatal-thalamic circuit

➢ PET imaging shows increased glucose metabolism in the orbital gyri

➢ It is postulated that orbitofrontal –thalamic hyperactivity gives rise to obsessive thoughts

11. AUTISM

➢ Limbic structures involved include the cingulate gyrus and amygdala, which mediate
cognitive and affective processing

➢ The basolateral circuit integral for social cognition is disrupted in autism spectrum
disorders

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 Neuroanatomy of Papez Circuit

Papez circuit

Fornix
Hippocampus
Mamillary body

Cingulum Mamillothalamic
Cingulate gyrus
tract
Anterior nucleus of
Thalamocingulate thalamus
tract

Introduction:
➢ James Papez’s delineation of a circuit after injecting rabies virus into a cat’s hippocampus
and monitoring its progression through the brain, unraveled the basis of cortical control of
emotion
➢ Further elaboration of the circuit has included the prefrontal cortex (PFC), amygdala and
septum among other areas
Functions:
➢ Learning, recent memory
➢ Hippocampus converts recent memory to long term memory
➢ Control of emotional behavior
➢ Feeling, feeding, fighting and fleeing activities
➢ Emotions necessary for sexual function (self preservation)
➢ Integrates olfactory, visceral, and somatic impulses through hypothalamus
➢ No olfactory function

Clinical anatomy

➢ Bilateral damage of hippocampus-anterograde amnesia

➢ Bilateral ablation of amygdala (and hippocampus)-
o Treatment of rage attacks in man
o Kluver Bucy syndrome- hyperphagia, docility, hypersexuality (in monkeys)

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➢ Korsakoff’s syndrome- lesion in mamillary bodies- amnestic confabulatory syndrome (severe
impairment of memory)
➢ Schizophrenia

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 Caudate nucleus

Anatomy:

• C shaped structure
• 3 regions- head body and tail
• Associated with contour of lateral ventricles (head- frontal horn of lateral ventricles
continuous with putamen, tail- temporal horn terminates in the amygdala)
• Located center of brain, sitting astride thalamus
• It is one of the structures that make up the dorsal striatum (with putamen), which is a
component of the basal ganglia. The caudate is also one of the brain structures, which
compose the reward system and functions as part of the cortico–basal ganglia–thalamic loop

❖ Neurochemistry:
Highly innervated by Dopamine neurons

❖ Motor functions:
o Spatial Mnemonic Processing (selective impairment in Parkinson’s disease)
o Directed movements
❖ Cognitive functions:
o Goal directed action
o Memory
o Learning
o Sleep
o Emotion
o Language
o Threshold control
❖ Clinical significance:
o Alzheimer’s disease
o Parkinson’s disease
o Huntington’s disease
o Attention-Deficit Hyperkinetic Disorder
o Schizophrenia
o Bipolar Type 1
o Obsessive compulsive disorder

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 Thalamus in Psychiatry

Introduction:

• Gatekeeper to the cortex

• Thalamus is an ovoid nuclear mass about 4 cm long
• Target of all sensory information (except olfaction) on its way to the cortex
• All subcortical structures project to the cortex via the thalamus
Anatomy:

• Paired structure
• Located on both sides of the third ventricle
• Mostly connected through interthalamic adhesion
• External Features and Relations:
a. Two ends or Poles- Anterior and posterior
b. Four surfaces- Medial, lateral, superior and inferior
Subdivisions of Thalamus:

A) Medial and lateral nucleus:

a. Internal medullary lamina divides thalamus into medial and lateral groups
of nuclei
b. Internal medullary lamina itself houses the inter laminar nuclei
c. Lamina splits into 2 halves anteriorly and encloses anterior nucleus of the
thalamus
d. Medial group- mediodorsal and medio-ventral nuclei
e. Lateral group-
1. Dorsal tier- lateral dorsal, lateral posterior, pulvinar
2. Ventral tier- ventral anterior, ventral posterior (ventral
posterolateral, ventral posteromedial), ventral lateral

B) Lateral and posterior nuclei

a. Lateral geniculate and medial geniculate

C) Surrounding nuclei
Thalamus is surrounded by a sheet of neurons which form the thalamic reticular
nucleus.

Functional classification of Thalamic nuclei

o Relay nuclei (receive input from periphery and pass onto cortex)
o Association nuclei (connect areas of cortex to one another)
o Other-
▪ Interlaminar (basal ganglia and limbic systems)
▪ Reticular nucleus (synchronizes thalamic activity with cortex)

Two types of inputs:

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 o Specific input contain input that need to be forwarded to cortex
o Regulatory inputs modulate and are much more in number than specific
Two types of firing pattern:

o Tonic firing (for linear transfer of information)

o Burst firing (detection of new/ changing stimuli). Burst firing increases during
sleep so as to decrease the amount of information related to cortex.
Functional division of major thalamic nuclei

Type Nucleus
Sensory Ventral postero-lateral (A- dorsal column, medial lemniscus, E-
somatosensory cortex)

Ventral posteromedial (A- face, trigeminal lemniscus, E-

somatosensory)

Lateral geniculate (A- visual optic tract,E- optic cortex)

Medial geniculate (A- auditory, inferior collicular ,E- auditory

cortex)
Motor Ventral anterior (A- Basal ganglia, cerebellum, E- motor,
premotor cortex)

Ventral lateral (A- Basal ganglia, cerebellum, E- motor,

premotor cortex)
Limbic Anterior (A- mammillothalamic, E- cingulate, prefrontal and
parietal)

Dorsomedial (A- entorhinal, E- cingulate, parietal)

Association Lateral dorsal (dorsolateral) DM

Lateral posterior- Pulvinar (A- Retina, visual and auditory

association area, parietal temporal frontal occipital association,
E- same)

Intralaminar Centromedian/ parafascicular (A- cholinergic ad dopaminergic

input from brain stem, E- striatum and diffusely to cortex)

Reticular A- Collaterals from corticothalamic and thalamocortical, E-

entire thalamus

Blood supply- Posterior cerebral artery

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173
Neuro-Psychiatric Aspects of Thalamus:

1. Dejerine Roussy Syndrome:

➢ CVAs can cause thalamic syndrome- Déjerine-Roussy syndrome

➢ Damage to the spinal tracts that carry pain and temperature sensation from the
periphery to the thalamus
➢ Thalamic pain starts several weeks after the stroke and presents as an intense
burning pain on the side of the body affected by the stroke and is often worsened
by cutaneous stimulation, often accompanied by mood swings
2. Chronic Pain:

➢ The DM nucleus is associated with the affective qualities of behavior and

somatic sensation through its connections with the hypothalamus and the
prefrontal cortex
➢ Removal of this nucleus and/or a prefrontal lobotomy may be used to modify
or reduce the emotional stress associated with chronic pain
3. Schizophrenia:

➢ Imaging studies have not established clearly whether there are volume differences in
subcortical structures in schizophrenia;

➢ Good evidence for a reduced size of the thalamus has emerged from postmortem
studies.

➢ Cytoarchitectural: replicated finding that the dorsomedial nucleus, which is part of a

circuit involving the prefrontal cortex, contains significantly fewer neurones than in
normal subjects

Robots syndrome:

➢ Rare
➢ Castaigne et.al
➢ Memory impairment (lack of attention), apathy, loss of social interest, Disturbance
of vigilance
➢ Bilateral symmetrical ischemic lesions of medial thalamic nu and mammillothalamic
tract

Vascular Dementia:

➢ The dysexecutive syndrome in vascular dementia includes impairment in goal

formulation, initiation, planning, organizing, sequencing, executing, set-sifting and
set-maintenance, as well as in abstracting-lesions affecting the prefrontal
subcortical circuit including prefrontal cortex, caudate, pallidum, thalamus, and the
thalamocortical circuit
Korsakoff’ Amnesic Syndrome:

➢ About 80 per cent of alcoholic patients recovering from Wernicke's encephalopathy

develop Korsakoff's amnesic syndrome
➢ Characterized by marked deficits in anterograde and retrograde memory, apathy,
an intact sensorium, and relative preservation of other intellectual abilities

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 ➢ Korsakoff's amnesic syndrome may also appear without an antecedent episode of
Wernicke's encephalopathy
➢ Histopathological lesions in the dorsomedial thalamus, anterior nucleus of
thalamus

Hepatic encephalopathy:

➢ The brains of patients with hepatic encephalopathy show enlargement and

proliferation of protoplasmic astrocytes in the basal ganglia, thalamus, red nucleus,
pons, and cerebellum, in the absence of neuronal loss or other glial changes

➢ Unilateral asterixis – in toxic encephalopathy co existing with structural lesions

(contralateral lesions of thalamus)

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 TEMPORAL LOBE FUNCTIONS

Dr Udayan Bhaumik

Introduction:

Location:

It is located on either side of the brain beneath the lateral sulcus of cerebral hemispheres. It
serves several important functions, especially the lateral temporal lobe which plays a role in
speech and the medial temporal lobe in memory

Medial Temporal Lobe:

➢ It has been functionally linked to long-term memory. These structures include the
hippocampus, entorhinal, perirhinal cortices as well as parahippocampal cortices
➢ Its main role is believed to be in declarative memory
➢ Recollection (conscious retrieval of previously learned information) is believed to occur
in the hippocampus
➢ Familiarity with memory contents is believed to be processed by the perirhinal cortex
➢ Spatial memory is processed in parahippocampal cortex
➢ The perirhinal cortex is anatomically well connected to the inferior temporal regions of
the ventral visual processing stream and parahippocampal cortex with the dorsal visual
stream and the auditory association cortices
➢ According to the multiple trace theory, hippocampus is involved in the retention and
retrieval of episodic memories over extended periods of time whereas some
researchers also believe its role to be more time-limited, with gradual transfer of
episodic memories from hippocampus to neocortex for long-term storage.
➢ The medial temporal lobe structures are also associated with high-level perception
➢ Visual discrimination impairments for complex objects may be observed after lesion in
the perirhinal cortices
➢ However various explanations for these phenomena are still being studied

Lateral temporal lobe:

➢ Superior temporal cortex in humans plays a vital role in speech sound processing
➢ This region contains the cortical representation of the auditory sensory system
➢ Bilateral lesions restricted to the superior temporal lobes result in the syndrome of
‘pure word deafness', characterized by a relatively isolated impairment of speech
sound discrimination
➢ Studies using positron emission tomography (PET) and functional magnetic
resonance imaging (fMRI) have demonstrated activation of the superior temporal
cortex bilaterally when subjects are presented with speech sounds in contrast to no
sounds
➢ From an information processing perspective, the perception of speech involves
several stages of auditory sensory analysis and pattern extraction as well as
interactions between sensory and stored linguistic information

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➢ The primary auditory cortex is largely confined to the caudal one- third of the
transverse temporal or Heschl's gyrus, suggesting a role for this region in early
sensory analysis of speech sounds. Heschel’s gyrus on the dorsal temporal surface,
is activated by all stimuli, whereas activation of the lateral surface of the superior
temporal gyrus is more variable across stimuli. The spatial extent of activation was
greatest for speech sounds, less for non-speech tones and least for noise
➢ The demonstration of a speech-specific response in left temporal lobe structures
suggests the existence of distinct subsystems within the auditory cortex, with
phonetic processing being principally carried out in the left superior temporal gyrus
and the perception of dynamic pitch variation (in music and speech) being dependent
on processes in the right superior temporal gyrus
➢ The results demonstrate that the dorsal–ventral model of human language
processing
➢ Also, Wernicke's area in the superior temporal cortex lies posterior to the plane of the
primary auditory cortex
➢ Access to word meaning is considered to be a major function of Wernicke's area.
This implies that the auditory word meaning pathway is directed posteriorly from the
primary auditory cortex
➢ Complex mental representations necessary for their unique identification are located
in the anterior ventral temporal lobe, with connections via the uncinate fasciculus to
prefrontal cortex
➢ Studies suggest that this same general anatomical organization underlies the
comprehension of speech
➢ The anterior superior temporal sulcus projects widely to high-order association cortex
and medial temporal lobe structures, diffusely distributed regions within which
associative knowledge about the meaning of words (i.e. semantic memory) is most
likely to be represented.

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 Parietal Lobe

Dr Udayan Bhaumik

Introduction:

Functional Anatomy:

➢ The parietal lobe underlies the parietal bone of the skull

➢ Its anterior border on the lateral aspect is marked by the central sulcus and its posterior
border by the parieto-occipital sulcus
➢ On the medial aspect it extends inferiorly to the cingulate gyrus, anteriorly to the central
sulcus, and posteriorly to the parieto-occipital sulcus
➢ The parietal lobe consists of the primary somatosensory cortex, the superior parietal
lobule, and the inferior parietal lobule
➢ The anterior parietal lobe, made up of the postcentral gyrus and posterior paracentral
lobule, is concerned with somatosensory sensations –touch, pain, temperature, and
limb position (proprioception)
➢ The posterior parietal lobe integrates somatosensory signals with signals from the
visual, auditory, and vestibular systems

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Functions:

The main functions of parietal lobe are:

1. Tactile functions (primary and secondary somatosensory cortex)

2. Eye movements (parietal eye field)

3. Spatial relations and right-left orientation

4. Calculations

5. Construction and other forms of praxis

6. Consciousness, body movements in space, self-awareness, episodic memory

retrieval, visuospatial imagery (praecuneus)

Parietal lobe dysfunction is seen in the following disorders:

Schizophrenia:

➢ Attention deficits are recognized in patients with schizophrenia

➢ Since the dorsal visual stream serves areas of the parietal lobe important in attention
it has been hypothesized that a defect in this system may underlie attention deficits in
this population
➢ Reduced activation of precuneus and inferior parietal lobule was also found in this
population and found to correlate with violence
➢ Episodic memory loss was found to be associated with precuneus atrophy.
Gerstmann Syndrome:

➢ Pantomime recognition (recognition of common gestures) may be lost following

damage to the dominant inferior parietal lobule
➢ A lesion involving the angular gyrus may produce part or all of Gerstmann syndrome:
1. Left–right confusion

2. Finger agnosia

3. Dysgraphia

4. Dyscalculia

Balint Syndrome:

➢ The patient with Balint syndrome is unable to process the visual field as a whole and
is fixed on only one part, a form of tunnel vision known as simultanagnosia
➢ Bilateral damage to the posterior inferior parietal lobule, often including adjacent
occipital cortex, may produce Balint syndrome
1. Optic apraxia –eyes tend to remain fixed on a visual target, although spontaneous
eye movements are unaffected
2. Optic ataxia –a deficit in using visual guidance to grasp an object
3. Simultanagnosia –seeing only the components of a visual object; unable to see the
object as a whole

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Tests for Parietal Lobe Function:

1. Object recognition

2. Eye movements

3. Calculations, reading and writing comprehension

4. Stereognosis, graphaesthesia

5. Gnosis and right-left confusion (by testing parts of body)

6. Praxis(ideational and ideomotor),truncal and limb apraxias-Eg:standing like a

boxer,light a candle

7. Picture description and construction of figures, Block design tests

8. Assessment of general sensations

References:

1)Georg Goldenberg: Apraxia and the parietal Lobes: Neuropsychologia 47 (2009) 1449–1459

2)Clark,Boutros and Mendez: The Brain and Behaviour: An introduction to Behavioural

Neuroanatomy:3rd edtn(1998)

3)Strub & Black:Mental Status Examination in Neurology:4th edtn(2000)

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 Corpus callosum

Introduction:

➢ It is a flat bundle of commissural fibres about 10 cm long located between and

beneath the cerebral cortices in the brains of placental mammals
➢ Spanning a part of the longitudinal fissure, it connects the left and right cerebral
hemispheres, and enables communication between the hemispheres
➢ It is the largest white matter structure in the human brain, consisting of 200–250
million axonal projections
Structure:

➢ The posterior end of the corpus callosum, near to the cerebellum, is called splenium.
➢ The thickest part, it overlaps the tela chorioidea of the third ventricle and the mid-
brain, ending in a thick, convex, free border
➢ Its anterior end near to the frontal lobes is called the genu. It is bent downward and
backward in front of the septum pellucidum
➢ It is prolonged backward under the name of the rostrum, and is connected below with
the lamina terminalis, which stretches from the interventricular foramina to the recess
at the base of the optic stalk
➢ The trunk of the corpus callosum is between the splenium and the genu
➢ A narrowed part between the body and the splenium is known as the isthmus of the
corpus callosum

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Connections:

➢ On either side of the corpus callosum, fibres radiate in the white matter and pass to
the various parts of the cerebral cortex, curving forward from the genu into the frontal
lobe to constitute the forceps anterior, and curving backwards into the occipital lobe
to form the forceps posterior
➢ Between these two parts is the main body of the fibres which constitute the tapetum
and extend laterally on either side into the temporal lobe, and cover in the central
part of the lateral ventricle.
Blood supply:

➢ Arterial supply is derived from two arterial systems, the primary being the carotid
system and secondary being the vertebrobasilar system. The carotid system is
represented by the pericallosal portion of the anterior cerebral artery distal to the
anterior communincating artery and in 20-80% cases, arising from it
➢ These two arterial systems give rise to numerous perforating arteries which divide
intricately to supply the corpus callosum
➢ Venous drainage is principally through the callosal and the callosocingulate veins

Functions:

182
 1. It is hypothesized to play a fundamental role in integrating information and mediating
complex behaviours
2. Believed to play a primary role in cognition
3. Weakened integrity of the callosum directly contributes to a decline in cognitive
function in aging adults whereas increased callosal thickness in typical childhood
development correlates with intelligence, processing speed and problem solving
abilities
4. It is also hypothesized that structural defects may play a role in Autistic Spectrum
disorders, ADHD and schizophrenia.
5. An intact corpus callosum contributes significantly to efficient executive function
6. Alterations in neuroanatomical connectivity (e.g. callosal fibres) is seen to cause
faulty functional coupling in a discrete frequency range (alpha; 8–12 Hz) both
between and within the cerebral hemispheres
Split Brain Syndrome:

➢ Studied first by Sperry, it is seen in partial or complete severing of corpus callosum

➢ It may be iatrogenic (as a treatment modality for intractable seizures practised
earlier) or traumatic, less common causes being cerebrovascular accidents and
Marchiafava-Bignami Disease
➢ Here, information cannot be exchanged between the two hemispheres, particularly
concerning speech and object recognition. Some of these may improve with time.
➢ Thus, corpus callosum has important neuropsychiatric implications, a lot of which is
still being studied.

References:

1. Divya Agrawal, Biswa Bhusan Mohanty, Sanjay Kumar, Prafulla Kumar Chinara:
Split brain syndrome: One brain but two conscious minds?. J Health Res Rev [serial online]
2014 [cited 2017 Nov 15];1:27-33.

2. Kakou M, Velut S, Destrieux C: [Arterial and venous vascularization of the corpus

callosum]: Neurochirurgie. 1998 May;44(1 Suppl):31-7.

3. Maria G Knyazeva: Review Article-Splenium of Corpus Callosum: Patterns of

Interhemispheric Interaction in Children and Adults: Neural Plasticity

Volume 2013 (2013), Article ID 639430

4. A Fitsiori, D Nguyen, A Karentzos,J Delavelle,and M I Vargas:The corpus callosum:

white matter or terra incognita: Br J Radiol. 2011 Jan; 84(997): 5–18.

5. Leighton B. N. Hinkley ,Elysa J. Marco ,Anne M. Findlay,Susanne Honma,Rita J.

Jeremy et al: The Role of Corpus Callosum Development in Functional Connectivity and
Cognitive Processing:plos.org: https://doi.org/10.1371/journal.pone.0039804

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 Ascending Reticular Activating System

Introduction:

➢ Consciousness is an arousal and awareness of environment and self, which is

achieved through action of the ascending reticular activating system (ARAS) on the
brain stem and cerebral cortex
➢ The reticular activating system is composed of several neuronal circuits connecting
the brainstem to the cortex
➢ These neuronal connections originate mainly in the reticular formation of the brainstem
and project through synaptic relays in the intralaminar nucleus of thalamus to the
cerebral cortex
➢ In addition, several brainstem nuclei like locus coeruleus, dorsal raphe, median raphe,
pedunculopontine nucleus, parabrachial nucleus, non-specific thalamic nuclei,
hypothalamus, and basal forebrain are also included in the ARAS system.
Role in Consciousness:

➢ Direct studies of the neurons involved in the sleep-wakefulness regulation, have

revealed membrane depolarization of the majority of cortical neurons, which is
performed by reticular activating system
➢ These neurons process and respond to the incoming signals from other neurons, both
at receptor and intracerebral level, only in a state of tonic depolarization
➢ Neocortical neurons require ascending tonic depolarization. Similarly, the spinal
motoneurons require descending depolarization for the maintenance of the muscle
tone. The latter is critical for position maintenance and voluntary movement
performance
➢ EEG studies show that cortical activation appears as suppression of all the slow
rhythms (δ, θ, α, and σ bands) in EEG, increase in a power of the β-band rhythms (15–
30 Hz), and synchronization of high-frequency rhythms in γ-band (30–60 Hz)
➢ Subsequently, the muscles tone increases, and baseline sympathetic tone emerges,
and the state of alertness appears
Neuro-anatomy and Neuro-chemistry of ARAS:

➢ The ascending reticular activating system (ARAS), containing glutamatergic,

cholinergic, aminergic, and hypocretinergic neurons
➢ It receives collateral fibres from the surrounding specific sensory systems
➢ The main long ascending pathway of the brainstem reticular formation is the central
tegmental tract, which projects to the intralaminar nucleus of thalamus
➢ Lesions in the rostro-medial midbrain tegmentum abolish the electroencephalographic
arousal reaction elicited by sensory stimulation even though the long ascending
sensory pathways remain intact
➢ The cerebral cortex acts in a top-down manner to alter the state of consciousness by
influencing the reticular neurons
➢ It is recognized as important in the induction and maintenance of rapid eye movement
(REM) sleep

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 ➢ The cholinergic neurons fire at the highest rate during wakefulness and REM sleep but
decrease their rates of firing at the onset of NREM sleep
➢ Noradrenergic neurons in the LC show the highest firing rates during wakefulness, the
lowest during REM sleep, and an intermediate rate during NREM sleep.
➢ The wakefulness-promoting aminergic neurons include:
1. Noradrenergic neurons in the locus ceruleus
2. Serotoninergic neurons in the dorsal raphe of the brain stem
3. Histaminergic neurons in the tuberomammillary nucleus of the hypothalamus
4. Possibly also dopaminergic neurons in the ventral tegmental area, substantia
nigra, and ventral periaqueductal area
5. Posterior hypothalamic histaminergic neurons are also believed to play a role in
wakefulness
The excitatory amino acids glutamic and aspartic acids, intermingled within the ARAS and
present in many neurons projecting into the cerebral cortex, forebrain, and brain stem, are
released maximally during wakefulness

The Hypocretin System:

➢ The discovery of hypothalamic hypocretin neurons with their widespread CNS

projections directs our attention to the role of the hypocretinergic system in controlling
sleep-wake regulation
➢ Hypocretin systems promote wakefulness mainly through excitation of
tuberomammillary histaminergic, LC noradrenergic, and midline raphe serotoninergic
and dopaminergic neurons
➢ Sleepiness may partly be induced by a reduction of activity of the hypocretin systems.
These neurons also participate in REM sleep regulation through activation of the
aminergic neurons (REM-off), which in turn inhibit REM-generating neurons.
References:

1)Clarke,Boutros and Menzes:The Brain and Behaviour-an Introduction to Behavioural

Neuroanatomy:3rd edtn

2)Vladimir m Kovalzon:Ascending Reticular Activating System of the brain: Translational

Neuroscience and Clinics: Vol. 2, No. 4, December 2016, pp 275–285

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 Autonomic Nervous system

Introduction:

➢ The autonomic nervous system regulates the various automatic processes in that
without conscious effort. Supplies all the major internal organs in the body.
➢ Has two main divisions:
1. Sympathetic
2. Parasympathetic
➢ After the autonomic nervous system receives information about the body and external
environment, it responds by stimulating body processes, usually through the
sympathetic division, or by inhibiting them, usually through the parasympathetic
division
➢ The functioning of the autonomic nervous system involves two neurons
➢ One cell is located in the brain stem or spinal cord. It is connected by nerve fibres to
the other cell, which is located in a cluster of nerve cells (called an autonomic
ganglion). Nerve fibres from these ganglia connect with internal organs
➢ Most of the ganglia for the sympathetic division are located just outside the spinal cord
on both sides of it
➢ The ganglia for the parasympathetic division are located near or in the organs they
connect with.
➢ The autonomic nervous system involves the action of two neurotransmitters,
acetylcholine and norepinephrine

Role in psychiatric disorders:

1. Anxiety disorders: Excessive and disordered firing of sympathetic nervous system
2. ANS and Psychiatric disorders:
➢ Evidence indicates that reductions in heart rate variability are found in individuals with
psychiatric disorders, including depression, schizophrenia, anxiety disorders and
substance dependence
➢ Meta-analysis by Alvares et al (2016) suggested ANS dysfunction to be a characteristic
feature in otherwise healthy patients with a major psychiatric disorder, with the largest
effects observed in patients with psychosis

3. Schizophrenia:
➢ Autonomic nervous system dysfunction and higher mortality in schizophrenia was
explored by Fujibayashi et al (2009) and he found autonomic system depression to
correlate positively with illness severity in schizophrenia, which explain increased rate
of adverse cardiovascular events and sudden cardiac death in schizophrenia
4. Depression:
➢ Dysregulation of the autonomic nervous system has been postulated in depression
➢ It is a known risk factor for medical morbidity and mortality in cardiac disease
➢ Medically well depressed psychiatric patients have found elevated levels of plasma
catecholamines and other markers of altered ANS function compared with controls
(Carney 2005)

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 ➢ Studies of depressed patients suffering from coronary heart disease has also shown
to have autonomic dysfunction like increased heart rate, decreased heart rate
variability, exaggerated heart rate responses to physical stressors, high variability in
ventricular repolarization, and low baroreceptor sensitivity
5. ANS and Psychotropics:
➢ He also noted that psychotropics have a small impact in further reducing heart-rate
variability in these populations, specifically associated with TCA and clozapine use
6. Heart rate variability and Psychiatric disorders:
➢ Patients with a psychiatric disorder have significantly increased rates of modifiable
lifestyle risk factors for cardiovascular disease, including obesity, diabetes,
hypertension, increased alcohol use and smoking as well as higher rates of major
physical health conditions, all of which may contribute to further reducing heart rate
variability in these populations
➢ Sudden cardiac death due to antipsychotics was also found be, at least partly, due to
autonomic dysregulation
➢ Autonomic functions may be partly controlled to reduce the symptoms of mental
illnesses. Techniques like mindfulness and biofeedback influence the regulation of
various autonomic processes by stimulating parasympathetic nervous system

References:
1. Philip Low:Overview of autonomic nervous system:msdmanuals.com
2. Gail A. Alvares,Daniel S. Quintana,an B. Hickie & Adam J. Guastella: Autonomic
nervous system dysfunction in psychiatric disorders and the impact of psychotropic
medications: a systematic review and meta-analysis: J Psychiatry Neurosci 2016;41(2)
3. Fujibayashi M, Matsumoto T, Kishida I, Kimura T, Ishii C, Ishii N, Moritani T:
Autonomic nervous system activity and psychiatric severity in schizophrenia:
Psychiatry Clin Neurosci. 2009 Aug;63(4):538-45
4. Hagit Cohen,Uri Lowenthal,Michael Matar & Moshe Kotler:Association of autonomic
dysfunction and Clozapine:Heart rate variability and risk ofsudden death in patients
with schizophrenia on long-term psychotropic medication:BJP(2001).179.167-171
5. Carney RM1, Freedland KE, Veith RC: Depression, the autonomic nervous system,
and coronary heart disease: Psychosom Med. 2005 May-Jun;67 Suppl 1:S29-33.

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 Basic Concepts Of Information Processing

Introduction:

The theory of information processing is derived from cognitive psychology. It compares the
human mind to a computer which takes information from the environment and assimilates it
after processing so that it may be reproduced in future.

Assumptions of Information Processing Theory:

(1) Information made available by the environment is processed by a series of processing

systems (e.g. attention, perception, short-term memory)

(2) These processing systems transform or alter the information in systematic ways

(3) The aim of research is to specify the processes and structures that underlie cognitive
performance

(4) Information processing in humans resembles that in computers

The process of attention can be understood by conceptualizing is to think of humans as

information processors who can only process a limited amount of information at a time without
becoming overloaded

Broadbent,in the 1950's, adopted a model of the brain as a limited capacity information
processing system, through which external input is transmitted

The Information Processing System has three components:

1. Input processes are concerned with the analysis of the stimuli.

2. Storage processes cover everything that happens to stimuli internally in the brain and
can include coding and manipulation of the stimuli.

3. Output processes are responsible for preparing an appropriate response to a

stimulus.

Information processing models assume serial processing of stimulus inputs:

1. Serial processing effectively means one process has to be completed before the next
starts.
2. Parallel processing assumes some or all processes involved in a cognitive task(s)
occur at the same time
General model of information processing has three components:

1. Sensory memory:

➢ Here, information is gathered through the senses through a process called

transduction

188
 ➢ Through receptor cell activity, it is altered into a form of information that the brain can
process
➢ These memories, usually unconscious, last for a very short amount of time, ranging up
to three seconds
➢ Our senses are constantly bombarded with large amounts of information
➢ The sensory memory acts as a filter, by focusing on what is important, and forgetting
what is unnecessary. Sensory information thus progresses into working memory, only
if it is seen as relevant or familiar.
2. Working /Short Memory:

1. Baddeley (2001) issued a model of working memory as consisting of three components

2. The executive controls system oversees all working memory activity, including
selection of information, method of processing, meaning, and finally deciding whether
to transfer it to long term memory or forget it
3. Two counterparts of this system are the auditory loop processing auditory information,
and the visual-spatial loop, where visual information is processed
4. Sensory memories transferred into working memory will last for 15-20 seconds, with a
capacity for 5-9 pieces of information
5. Information is maintained in working memory through maintenance or elaborative
rehearsal. Maintenance refers to repetition, while elaboration refers to the organization
of information (such as chunking or chronology)
6. The processing that occurs in working memory is affected by various factors
7. Individuals have varying levels of cognitive load, or the amount of mental effort they
can engage in at a given moment, due to individual characteristics and intellectual
capacities
8. Secondly, information that has been repeated many times becomes automatic and
thus does not require much cognitive resources (e.g. riding a bike)
9. Lastly, according to the task at hand, individuals use selective processing to focus
attention on information that is highly relevant and necessary
3. Long term Memory:

➢ Long term memory includes various types of information: declarative (semantic and
episodic), procedural, and imagery
➢ As opposed to the previous memory constructs, long term memory has unlimited space
➢ The crucial factor of long term memory is how well organized the information is
➢ This is affected by proper encoding (elaboration processes in transferring to long term
memory) and retrieval processes (scanning memory for the information and
transferring into working memory so that it could e-used)
➢ As emphasized in Bransford’s work, the degree of similarity between the way
information was encoded and the way it is being accessed will shape the quality of
retrieval processes.
➢ These basic concepts have been utilized and used to explain information processing
➢ Research in this field is happening and should give a better understanding of how
these processes actually happen

189
Fig: Model of Information Processing

References

1. Saul Mcleod: Information Processing:2008:

2. Miller et al: Information Processing Theory

190
 Blood Supply Of The Brain

Introduction:

➢ The entire blood supply of the brain is derived from two sets of arteries from the dorsal
aorta
➢ The entire blood supply of the brain and spinal cord depends on two sets of branches
from the dorsal aorta:
1. The vertebral arteries arise from the subclavian arteries
2. Internal carotid arteries are branches of the common carotid arteries
➢ The vertebral arteries and the ten medullary arteries that arise from segmental
branches of the aorta provide the primary vascularization of the spinal cord
➢ These medullary arteries join to form the anterior and posterior spinal arteries. If any
of the medullary arteries are obstructed or damaged, the blood supply to specific parts
of the spinal cord may be compromised. The pattern of resulting neurological damage
differs according to whether the supply to the posterior or anterior artery is interrupted.
➢ The major branches that arise from the internal carotid artery—the anterior and middle
cerebral arteries—form the anterior circulation that supplies the forebrain. These
arteries also originate from the circle of Willis
➢ Each gives rise to branches that supply the cortex and branches that penetrate the
basal surface of the brain, supplying deep structures such as the basal ganglia,
thalamus, and internal capsule
➢ Lenticulostriate arteries that branch from the middle cerebral artery supply the basal
ganglia and thalamus
➢ The posterior circulation of the brain supplies the posterior cortex, the midbrain, and
the brainstem; it comprises arterial branches arising from the posterior cerebral,
basilar, and vertebral arteries. The pattern of arterial distribution is similar for all the
subdivisions of the brainstem:
1. Midline arteries supply medial structures
2. Lateral arteries supply the lateral brainstem
3. Dorsal-lateral arteries supply dorsal-lateral brainstem structures and the
cerebellum
➢ Among the most important dorsal-lateral arteries (also called long circumferential
arteries) are the posterior inferior cerebellar artery (PICA) and the anterior inferior
cerebellar artery (AICA), which supply distinct regions of the medulla and pons
➢ These arteries, as well as branches of the basilar artery that penetrate the brainstem
from its ventral and lateral surfaces (called paramedian and short circumferential
arteries), are especially common sites of occlusion and result in specific functional
deficits of cranial nerve, somatic sensory, and motor function.
Circle of Willis:

➢ It is formed in front by the anterior cerebral arteries, branches of the internal carotid
artery, which are connected together by the anterior communicating branches; behind
by the two posterior cerebral arteries, branches of the basilar artery, which are

191
 connected on either side with the internal carotid by the posterior communicating
arteries
➢ The lamina terminalis, the optic chiasma, the infundibulum, the tuber cinereum, the
corpora mammillaria, and the posterior perforated substance lie within this anastomotic
network
➢ It is rarely seen radiographically in its entirety; anatomical variations are very common
and a well-developed communication between each of its parts is identified in less than
half of the population
➢ Asymmetry of the circle of Willis results in significant asymmetry of flow and is an
important factor in the development of intracranial aneurysms and ischemic stroke
➢ Patients with aneurysms are more likely to have asymmetry or an anomaly of the circle
➢ Uncommonly, persistence of fetal anastomoses involving the circle of Willis is found,
including persistent trigeminal, otic, hypoglossal, and proatlantal arteries

192
Cortical arterial system:

➢ The terminal branches of the anterior, middle, and posterior cerebral arteries form the
cortical system. They divide and ramify in the substance of the pia mater, and give off
branches which penetrate the brain cortex perpendicularly
➢ These branches are divisible into two types like long and short. The long or medullary
arteries pass through the gray matter and penetrate the subjacent white substance to
the depth of 3 or 4 cm, without intercommunicating others and thus constitute so many
independent small systems. The short vessels are confined to the cortex, where they
communicate with the long vessels to form compact net-work in the middle zone of the
gray matter, the outer and inner zones being sparingly supplied with blood
➢ Vessels of the cortical arterial system are not terminal arteries like ganglionic system,
preventing widespread effect on the cortex in case of ischaemia
Ganglionic arterial system:

➢ All the vessels of this system are given off from the arterial circle of Willis or from the
vessels close to it
➢ They form six principal groups:
✓ Anteromedial group, derived from the anterior cerebral arteries and anterior
communicating branch
✓ Postero-medial group, from the posterior cerebral arteries and posterior
communicating branches
✓ Right and left antero-lateral groups, from the middle cerebral arteries
✓ Right and left postero-lateral groups, from the posterior cerebral arteries around
the cerebral peduncles
➢ Unlike cortical arteries,these ar terminal in nature
Blood brain barrier:

The blood brain barrier forms a tight between the capillaries and the tissue of brain interface

In addition to tight junctions, astrocytic surround the outside of capillary endothelial cells

The reason for this endothelial—glial allegiance is unclear, but may reflect an influence of
astrocytes on the formation and maintenance of the blood-brain barrier.

Fig 1:Blood Brain barrier:

193
194
 Cerebral dominance

Introduction:

➢ The nature of asymmetric functioning of the human brain came in to being due to the
increased prevalence of right handers
➢ Because the left hemisphere was found to control the right hand, found dominant in
most individuals, it came to be known as the dominant hemisphere
➢ Later, evidence that the right hemisphere was the more specialized for perception and
emotion also led to idea about the complementary roles of the two sides of the brain
in maintaining psychological equilibrium
➢ Testing of each disconnected hemispheres in patients callosectomised for refractory
seizures again revealed the left to be specialized for language and the right for
emotional and nonverbal functions
Evolution with language implications:

➢ Right-left asymmetry of brain has been seen in both vertebrates and invertebrates
➢ These can arise due to neural, genetic or epigenetic mechanisms
➢ A right-handed cerebral dominance for emotion has been found in all primates and
may relate to left dominance for language
Inborn asymmetry:

➢ Handedness and cerebral asymmetries are detectable in the foetus

➢ Ultrasound recording has shown that by the tenth week of gestation, majority of
foetuses move the right arm more than the left, and from the 15th week most suck the
right thumb rather than the left. In these prenatal brain asymmetries, around two-thirds
of cases show the leftward bias
➢ The same ratio applies to the asymmetry of the temporal planum in both infants and
adults
Variations in asymmetry:

➢ Handedness and cerebral asymmetry are not only variable, they are also imperfectly
related
➢ Some 95–99 percent of right-handed individuals are left-brained for language, but so
are about 70 percent of left-handed individuals

195
 ➢ Even at rest, the human brain exhibits asymmetry in functioning with different regions
➢ Although handedness has been, in part, believed to be explained due to genetic
influence, he manner in which handedness is inherited has been most successfully
modelled by supposing that a gene or genes influence not whether the individual is
right- or left-handed, but whether a bias to right-handedness will be expressed or not
➢ In those lacking the “right shift” bias, the direction of handedness is a matter of chance
and not likely to be influenced genetically
➢ Linkage analyses have often revealed candidate laterality genes, but all too often these
fail in follow-up analysis—a common problem in the search for genes related to human
behaviour
➢ Two such candidate genes identified are PCSK6 and LRRTM1
➢ Rearrangement between X and Y chromosomes is also believed to be involved in
handedness.
Conclusions:

➢ Genetic considerations aside, departures from right-handedness or left-cerebral

dominance have sometimes been linked to disabilities
➢ Ambidextrity has been found to be associated with stammering, poor academic skills
and as well as schizophrenia. However, regarding left-handed individuals as deficient
or contrarian may be based more on prejudice than on the facts.

References:

• Michael C. Corballis Left Brain, Right Brain: Facts and Fantasies:plos.org:2014

• J. J. Fleminger and l. Bunce: Investigation of cerebral dominance in 'left-handers' and

'right-handers' using unilateral electroconvulsive therapy: Journal of Neurology,
Neurosurgery, and Psychiatry, 1975, 38, 541-545

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 Cerebral laterality

Introduction: There exists a variation in terms of anatomy and functioning of the right and left
cerebral hemispheres.

This asymmetry is present at the structural level of not only humans but also other primates
and from the newborn period.

Anatomical differences:

Initially demonstrated and later further studies,the detectable asymmetry was found to be
localized primarily to the upper surface of the posterior portion of temporal lobe.Because this
region,the plenum temporale,constitutes a large portion of Wernicke’s area,localization of
speech is lateralised to the left hemisphere in most humans.

Gender differences:

Brain laterality differences between the genders have also been documented and may
underlie gender differences in cognitive styles.For eg, the females' overall linguistic
advantage over males may reflect stronger leftward lateralization of the language networks.On
the other hand, the males' spatial skills advantage over females may reflect stronger rightward
lateralization of visuospatial networks. Gender differences in the lateralization of brain function
might also contribute to gender differences in the incidence of various neurospychiatric
disorders.

Psychiatric aspects:

➢ Disordered right-left laterality is believed to play a role in the pathogenesis of disorders

like autism spectrum disorders and schizophrenia. However how exactly it plays a role
is uncertain.
➢ In 1925 Orton had suggested developmental reading problems might be the result of
a poorly lateralized brain. This link was developed more fully in the 1980s, when Annett
formulated a detailed genetic theory of lateralization that linked developmental dyslexia
and language disorders to specific genotypes of a postulated ‘right shift’ factor. Prior
to the development of modern neuroimaging, the only reliable way of assessing
cerebral lateralization in an individual was the Wada technique, an invasive pre-
surgical procedure in which anaesthetic would be injected into one carotid artery to
produce a transient inactivation of the corresponding hemisphere.

197
 ➢ It is commonly asserted as fact that left-handedness is associated with conditions such
as dyslexia, and that handedness is highly heritable, and yet the evidence for both
claims is lacking.
➢ Moreover, relationship between handedness and laterality is imperfect. With the
advent of newer neuroimaging techniques, it has become possible to focus on these
aspect
➢ However, till now, most of the studies have focussed on structural brain asymmetry.

Genetic contribution:

➢ Developmental language and literacy disorders are heritable, and the pattern of
inheritance suggests they are complex multifactorial disorders, caused by the
combined action of many genes and environmental risk factors, each of small effect
➢ Based on endophenotype model, possibility that the genetic risk for dyslexia and SLI
can be hypothesized to be mediated by an effect on cerebral lateralization
➢ Pleiotropy model, on the other hand, states that the same genes that act as risk factors
for language problems also affect cerebral lateralization, but it does not entail that
cerebral lateralization mediates the relationship between genes and language
problems
➢ Among the language associated single nucleotide polymorphisms, CNTNAP2 showing
some evidence of lateralized effects
Conclusions:

➢ Overall, the evidence for genes affecting individual differences in cerebral lateralization
is not strong – both in terms of twin study data, and genetic variants associated with
phenotypic variation
➢ However, the idea that genetic variants are implicated in cerebral lateralization cannot
be dismissed
➢ Atypical lateralization may add or interact with genetic risk for language and cognitive
impairments; second, the asymmetry phenotype could differ for those who have
language impairments and the remainder of the population.
References:

1. Dardo Tomasi & Nora D. Volkow: Laterality Patterns of Brain Functional Connectivity:
Gender Effects: Cerebral Cortex, Volume 22, Issue 6, 1 June 2012, Pages 1455–1462
2. Norman Geschwind & Walter Levitsky: Human Brain: Left-Right Asymmetries in
Temporal Speech Region: Science 12 Jul 1968,Vol. 161, Issue 3837, pp. 186-187
3. Norman Geschwind & Albert M. Galaburda: Cerebral Lateralization:Biological
Mechanisms, Associations, and Pathology: I. A Hypothesis and a Program for
Research: Arch Neurol. 1985;42(5):428-459
4. Dorothy v M Bishop: Cerebral asymmetry and language development: cause, correlate
or consequence?: Science. 2013 Jun 14; 340(6138): 1230531.

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 Cortical control of Eye movements

Introduction:

➢ Eye movement research has advanced in recent years due to use of newer investigation
modalities like transcranial magnetic stimulation and functional magnetic resonance imaging
➢ However, older methods still provide a lot of valuable information as lesion studies remain
the best markers for brain area involvement
Frontal lobe:

➢ The areas controlling eye movements in frontal lobe are:

1. Frontal eye field

2. Supplementary eye field

3. Dorsolateral prefrontal cortex

➢ Frontal eye field:

a) It is involved in the preparation and triggering of all intentional saccades, which are
internally triggered towards an already present target
b) It is less involved in the triggering of reflex visually guided saccades, which is mainly
a function of parietal eye field
c) It also controls smooth pursuit movements, along with the parieto-temporal areas
d) The frontal eye field is located mainly at the intersection of precentral and superior
frontal sulci
e) A lateral locus of activation, along the lateral part of precentral sulcus and adjacent
portion of precentral gyrus has been noticed in fMRI and found to be activated by
both head and eye movements.
Pursuits:

➢ These areas appear to be located in the precentral sulcus, more posterior to the stimulation
site for saccades
Supplementary eye field:
➢ Located on the medial surface of the superior frontal gyrus
➢ In humans, it is located in the upper part of the para-central sulcus
➢ Anatomically it appears to be a critical node in the oculomotor circuit

199
 ➢ Supplementary eye field is connected with all areas involved in eye movement control—the
frontal eye field, the dorsolateral prefrontal cortex, the anterior cingulate cortex, most of
the parietal cortex, and also deep oculomotor structures in the brainstem
➢ Electrical stimulation in monkeys and lesion studies in humans have demonstrated that
supplementary eye field is involved in motor program comprising a saccade combined with a
body movement

Dorsolateral prefrontal cortex:

➢ It is involved in saccade inhibition, but plays its part in short-term spatial memory and in
decision processes
➢ Human and nonhuman primate studies have demonstrated that the dorsolateral prefrontal
cortex, and, more particularly, area 46 of Brodmann and the adjacent Brodmann area 9,
both located in the middle frontal gyrus, are involved in the control of memory-guided
saccades
➢ It serves the crucial role of decisional processes governing eye movement behaviour,
preparing intentional saccades by inhibiting unwanted reflexive saccades (inhibition),
maintaining memorized information for forthcoming intentional saccades (short-term spatial
memorization), or facilitating intentional anticipatory saccades
Parietal Lobe:

➢ In the parietal lobe, the location and function of regions involved in eye movements and
attention have been studied intensively, but are still not so well known
➢ The parietal lobe and more particularly its posterior part, are involved in the control of
saccades and attention
➢ As it has been noticed in supplementary eye field, the activation of the parietal eye field is
also modulated by head position
➢ The parietal eye field projects to both the frontal eye field and the superior colliculus
➢ In monkeys, these two projections appear to be qualitatively different, with a more visual
involvement for the parieto-FEF projection and a more saccadic involvement for the
parietosuperior colliculus projection
➢ The parieto-FEF projection is believed to be mainly involved in visual processing, whereas
the parietocolliculus projection is more involved in express saccades
Cingulate Cortex:

➢ Finally, the cingulate cortex has also been found to have an important role in the control of
voluntary saccades
➢ The rostral part of the cingulate cortex is involved in intentional saccade control, but not in
reflexive saccade control
➢ The dorsal bank of the anterior cingulate cortex is involved, via direct connections to
supplementary eye field, in preparing all the frontal ocular motor areas involved in
intentional saccade control to act in the forthcoming motor behaviour. It is densely
connected to Dorsolateral prefrontal cortex
Current understanding:

200
 ➢ Current idea regarding eye movement control postulates that in the frontal cortex, frontal
eye field is believed to be involved for the execution of intentional saccades
➢ The neuronal responses present in frontal eye field are prepared by the activities in
supplementary eye field, anterior cingulate cortex, and dorsolateral prefrontal cortex,
whereas the parietal lobe, through the posterior part of the internal capsule, is believed to
be sufficient to elicit reflexive saccades
➢ However the hierarchy between the various cortices for the same role requires more
understanding
References
1)P.Pouget: The cortex is in overall control of ‘voluntary' eye movement: Eye (Lond). 2015 Feb;
29(2): 241–245.

2) Charles Pierrot-Deseillignya , Dan Mileab and Rene M. Muri:Eye Movement Control by the
cerebral cortex: Current Opinion in Neurology 2004, 17:17–25

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 Cerebro-spinal fluid (CSF)

Introduction:

➢ It is produced and secreted by the choroid plexus of the ventricles of brain and absorbed by
the arachnoid granulations
➢ The bran volume of CSF is about 125 ml, while 500 ml is produced everyday
➢ It plays the role of a buffer inside the brain, thus providing mechanical and immunological
protection
➢ It also serves to autoregulate cerebral blood flow
Location:

➢ CSF occupies the subarachnoid space (between the arachnoid mater and the pia mater) and
the ventricular system around and inside the brain and spinal cord
➢ It fills the ventricles of the brain, cisterns, and sulci and is continuous with the central canal
of the spinal cord
➢ There is also a connection from the subarachnoid space to the bony labyrinth of the inner
ear via the perilymphatic duct where the perilymph is continuous with the cerebrospinal
fluid.
Drainage:

➢ Most of the CSF is produced from within the two lateral ventricles
➢ Thereafter the CSF passes through the interventricular foramina to the third ventricle, then
the cerebral aqueduct to the fourth ventricle
➢ From the fourth ventricle, the fluid passes into the subarachnoid space through four
openings – the central canal of the spinal cord, the median aperture, and the two lateral
apertures
Importance in Psychiatry:

➢ Numerous studies have been done to find out the relationship of CSF with various mental
illnesses
➢ Biomarkers in CSF are being studied for potential use as predictors for various mental
illnesses and also to understand their pathophysiology
➢ Core cerebrospinal fluid (CSF) biomarkers for Alzheimer’s Disease, namely total tau,
phosphorylated tau and the 42 amino acid form of amyloid-β have been found to reflect
disease pathology, and are candidate markers for predicting future cognitive decline in
healthy individuals and the progression to dementia in patients who are cognitively impaired

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 ➢ CSF anandamide levels correlated inversely with psychotic symptoms, suggesting that
anandamide release in the central nervous system (CNS) may serve as an adaptive
mechanism countering neurotransmitter abnormalities in acute psychoses
➢ Somatostatin dysregulation in the most consistently observed biological abnormality in
depression and schizophrenia, believed to cause dexamethasone suppression in these
individuals.
➢ Inflammatory markers like IL_6, TNF-beta and interferons have also been found in increased
levels in CSF suggesting a pro-inflammatory pathology for these mental illnesses
➢ Cerebrospinal fluid levels of the major central metabolites of serotonin, norepinephrine, and
dopamine-particularly low levels of 5-hydroxyindoleacetic acid and elevated levels of
methoxy-4 -hydroxy phenylglycol have been found to correlate with increased aggression,
which suggests the future use of thse markers as predictors of violence and mental illness in
both hospital and society settings
➢ Patients in the low 5-HIAA (below 15 ng/ml) have also been found to attempt suicide
significantly more often than those in the high range, and they used more violent methods
for the act
Diagram of CSF Flow:

203
204
References:

a) Kaj Blennow, Harald Hampel, Michael Weiner& Henrik Zetterberg: Cerebrospinal fluid and
plasma biomarkers in Alzheimer disease: Nature Reviews Neurology 6, 131–144 (2010)
b) Marie Åsberg, Lil Träskman, Peter Thorén 5-HIAA in the Cerebrospinal Fluid:A Biochemical
Suicide Predictor?: Arch Gen Psychiatry. 1976;33(10):1193-1197
c) Gerald L.Brown1∗Frederick K.Goodwin2∗James C.Ballenger3∗Peter F.Goyer4∗Leslie
F.Major5∗: Aggression in humans correlates with cerebrospinal fluid amine
metabolites:Psychiatry Reasearch,Volume 1,Issue 2,Oct 1979,pg131-39
d) Rosén, Christoffera; Zetterberg, Henrik:Current Opinion in Psychiatry: May 2013 - Volume 26
- Issue 3 - p 276–282: Cerebrospinal fluid biomarkers for pathological processes in
Alzheimer's disease
e) Claire Paquet, Eloi Magnin,, David Wallon et al: Utility of CSF biomarkers in psychiatric
disorders: a national multicentre prospective study: Alzheimer's Research &
Therapy20168:27

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 TEMPORAL LOBE FUNCTIONS

Introduction:

Location:

It is located on either side of the brain beneath the lateral sulcus of cerebral hemispheres. It serves
several important functions, especially the lateral temporal lobe which plays a role in speech and the
medial temporal lobe in memory

Medial Temporal Lobe:

➢ It has been functionally linked to long-term memory. These structures include the
hippocampus, entorhinal, perirhinal cortices as well as parahippocampal cortices
➢ Its main role is believed to be in declarative memory
➢ Recollection (conscious retrieval of previously learned information) is believed to occur in
the hippocampus
➢ Familiarity with memory contents is believed to be processed by the perirhinal cortex
➢ Spatial memory is processed in parahippocampal cortex
➢ The perirhinal cortex is anatomically well connected to the inferior temporal regions of the
ventral visual processing stream and parahippocampal cortex with the dorsal visual stream
and the auditory association cortices
➢ According to the multiple trace theory, hippocampus is involved in the retention and
retrieval of episodic memories over extended periods of time whereas some researchers
also believe its role to be more time-limited, with gradual transfer of episodic memories
from hippocampus to neocortex for long-term storage.
➢ The medial temporal lobe structures are also associated with high-level perception
➢ Visual discrimination impairments for complex objects may be observed after lesion in the
perirhinal cortices
➢ However various explanations for these phenomena are still being studied

Lateral temporal lobe:

➢ Superior temporal cortex in humans plays a vital role in speech sound processing
➢ This region contains the cortical representation of the auditory sensory system
➢ Bilateral lesions restricted to the superior temporal lobes result in the syndrome of ‘pure
word deafness', characterized by a relatively isolated impairment of speech sound
discrimination
➢ Studies using positron emission tomography (PET) and functional magnetic resonance
imaging (fMRI) have demonstrated activation of the superior temporal cortex bilaterally
when subjects are presented with speech sounds in contrast to no sounds
➢ From an information processing perspective, the perception of speech involves several
stages of auditory sensory analysis and pattern extraction as well as interactions between
sensory and stored linguistic information

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➢ The primary auditory cortex is largely confined to the caudal one- third of the transverse
temporal or Heschl's gyrus, suggesting a role for this region in early sensory analysis of
speech sounds. Heschel’s gyrus on the dorsal temporal surface, is activated by all stimuli,
whereas activation of the lateral surface of the superior temporal gyrus is more variable
across stimuli. The spatial extent of activation was greatest for speech sounds, less for non-
speech tones and least for noise
➢ The demonstration of a speech-specific response in left temporal lobe structures suggests
the existence of distinct subsystems within the auditory cortex, with phonetic processing
being principally carried out in the left superior temporal gyrus and the perception of
dynamic pitch variation (in music and speech) being dependent on processes in the right
superior temporal gyrus
➢ The results demonstrate that the dorsal–ventral model of human language processing
➢ Also, Wernicke's area in the superior temporal cortex lies posterior to the plane of the
primary auditory cortex
➢ Access to word meaning is considered to be a major function of Wernicke's area. This
implies that the auditory word meaning pathway is directed posteriorly from the primary
auditory cortex
➢ Complex mental representations necessary for their unique identification are located in the
anterior ventral temporal lobe, with connections via the uncinate fasciculus to prefrontal
cortex
➢ Studies suggest that this same general anatomical organization underlies the comprehension
of speech
➢ The anterior superior temporal sulcus projects widely to high-order association cortex and
medial temporal lobe structures, diffusely distributed regions within which associative
knowledge about the meaning of words (i.e. semantic memory) is most likely to be
represented.

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 Lobe Function Tests

Introduction:

➢ Lobe function tests are relevant in Psychiatry to systematically assess neuropsychiatric

functions pertaining to individual lobes and to delineate deficits related to them
➢ They are important to target through cognitive exercises, to mark improvement, to relate to
symptoms due to an organic etiology related to lobar function
➢ They also carry neuropsychological and legal importance. Bedside evaluation of these lobes
helps us to understanding the deficit area in a better way and correlate with neuroimaging
Frontal lobe tests:

Bedside tests:

1. Motor strength of hand grip. The patient is asked to grip the examiners fingers. Strength should
be roughly equal, with greater strength on the dominant side. It should be difficult for the examiner
to free her/his fingers.

2. Motor speed as in finger tapping has also been listed as a useful test but such tests do not
discriminate from the premotor cortex.

Premotor Cortex:

Bedside tests:

1. Sensorimotor abilities are tested by asking the patient touch each finger to the thumb in
succession as rapidly as possible. Watch for speed and dexterity.

2. Apraxia can be tested by asking the patient to "blow a kiss" and to demonstrate the use of a
shovel.

Frontal Eye field:

1. The patient is asked to follow the movement of a finger from left to right and up and down.

2. The patient to look from left to right, up and down with no finger to follow. Inability to move or
jerky movements should be assessed.

Dorsolateral Prefrontal Cortex:

1. Tests of attention, like finger tapping on hearing a particular letter, crossing out 6s and
9s, serial 100-7,40-3,20-1, days or months backwards.

2. Controlled oral word association test (COWAT): the patient is asked to produce as many
words as possible, in one minute, starting with F, then A, then S. Proper nouns and
previously used words with a different suffix are prohibited.

3. Tests for phonemic and categorical fluency

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4.Alternating hand sequences(fist-edge-palm) or figure copying with repetitive patterns

5.Wisconsin card sorting test-tests set shifting

Orbitofrontal cortex:

1.Testing familiar odours

2.Go/No go test-The patient is asked to make a response to one signal (the Go signal) and not to
respond to another signal (the no-go signal).

3.Stroop Test-Patients are asked to state the colour in which words are printed rather than the
words themselves. It tests response inhibition.

Frontal Release reflexes:

Glabellar tap,snout,suckling and rooting reflex,palmomental reflexes.

Temporal Lobe testing:

1)Language functions-repetition of words, sentences for working memory testing

2)Visual Recognition-Identifying different unrelated objects, pictures of famous personalities for

prosopagnosia

3)Auditory-Identifying various familiar melodies

4)Semantic Memory-Facts related to familiar settings

Parietal Lobe testing:

1)Finger Agnosia-Inability to point and identify fingers

2)Astereognosis, Agraphaesthesia

3)Figure, clock drawing and block Design-tests for constructional apraxia

4)Asomatognosia-Inability to recognize and name various body parts

5)Visual Field Testing

6)Comprehension in reading and writing

Reference:

• Strub & Black:The Mental Status Examination in Neurology:4th edtn(2000)

• https://eprints.utas.edu.au/287/32/Chapter_27__Frontal_lobes_-_bedside_testing.pdf

209
 Medial Longitudinal Fasciculus

Introduction:

➢ The medial longitudinal fasciculus is one of a pair of crossed fibre tracts on each side of
brainstem
➢ These bundles of axons are situated near the midline and are composed of both ascending
and descending fibres arising from various sources and terminate in different areas
➢ It serves a s the central connection for cranial nerves III, IV and VI with vertical gaze centre
being localised to rostral interstitial nucleus
Function:

➢ It determines the direction of movement of the eyes

➢ It integrates the functions of the nuclei of cranial nerves III, IV and VI with that of frontal eye
field and head movement governed by the VIII cranial nerve
➢ It serves as the integral component for saccadic movements as well as vestibulo-ocular and
optokinetic reflexes
➢ It also carries the descending tectospinal tract and medial vestibulospinal tracts into the
cervical spinal cord, and innervates some muscles of the neck and upper limbs playing a role
in visual coordination
Importance in Psychiatry:

➢ Clinically, lesion at the medial longitudinal fasciculus produces slowed or absent adduction
of the ipsilateral eye, usually associated with nystagmus of the abducting eye, a syndrome
called internuclear ophthalmoplegia
➢ In multiple sclerosis, demyelination of the axons in central nervous system can cause
internuclear ophthalmoplegia when the concerned axons get de-myelinated, presenting as
nystagmus and diplopia
➢ Bilateral lesions are usually associated with demyelinating processes but also observed in
occlusive vascular disorders and in neoplasms
➢ Vertical nystagmus is usually present on upgaze, and convergence may or may not be
preserved. Skew deviation is rarely observed
➢ Unilateral lesions are more common in occlusive diseases. In these cases, the weakness of
adduction is seen ipsilateral to the side of the lesion
➢ Abduction nystagmus is usually present contralateral to the and vertical nystagmus occurs
frequently
➢ Convergence is preserved. Skew deviation is common with the elevated eye usually on the
side of the lesion. Vertical gaze is usually preserved.
➢ The lateral paramedial pontine reticular formation, believed to be the source of integration
of both voluntary and reflex conjugate horizontal eye movements, along with the cerebral
hemispheres, is thought to generate a checking or fast component in the direction opposite
to the slow component that determines the direction of the specified nystagmus.
➢ This area is also known to be rich in serotonergic neurons and is one of the areas noted to be
show predilection for deposition of neurofibrillary tangles in Alzheimer’s Disease.

210
 ➢ Saccadic function involvement:
It has been noted in Parkinson’s Disease and schizophrenia

In schizophrenia, their examination may not be very reliable due to patients being on dopaminergic
blockers, but increased distractibility to the anti-saccadic task has been noted to be reliable as it is
seen in drug-induced Parkinsonism

It is also marked in tardive dyskinsesia and may be responsible for perseveration and set-shifting
difficulties seen in schizophrenia

References:

1. C Kennard, T J Crawford, l Henderson:A pathophysiological approach to saccadic eye movements

in neurological and psychiatric disease: J'ournal of Neurology, Neurosurgery, and Psychiatry
1994;57:881-885
2. L. R. Jenkyn, G. Margolis,A. G. Reeves: Reflex vertical gaze and the medial longitudinal fasciculus:
Journal ofNeurology, Neurosurgery, and Psychiatry, 1978, 41, 1084-1091
3. David Mamann & Peter O Yates:Serotonin nerve cells in Alzheimer's disease: Journal of
Neurology, Neurosurgery, and Psychiatry 1983;46:96-98

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 Parietal Lobe

Introduction:

Functional Anatomy:

➢ The parietal lobe underlies the parietal bone of the skull

➢ Its anterior border on the lateral aspect is marked by the central sulcus and its posterior
border by the parieto-occipital sulcus
➢ On the medial aspect it extends inferiorly to the cingulate gyrus, anteriorly to the central
sulcus, and posteriorly to the parieto-occipital sulcus
➢ The parietal lobe consists of the primary somatosensory cortex, the superior parietal lobule,
and the inferior parietal lobule
➢ The anterior parietal lobe, made up of the postcentral gyrus and posterior paracentral
lobule, is concerned with somatosensory sensations –touch, pain, temperature, and limb
position (proprioception)
➢ The posterior parietal lobe integrates somatosensory signals with signals from the visual,
auditory, and vestibular systems

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Functions:

The main functions of parietal lobe are:

6. Tactile functions (primary and secondary somatosensory cortex)

7. Eye movements (parietal eye field)

8. Spatial relations and right-left orientation

9. Calculations

10. Construction and other forms of praxis

6. Consciousness, body movements in space, self-awareness, episodic memory retrieval,

visuospatial imagery (praecuneus)

Parietal lobe dysfunction is seen in the following disorders:

Schizophrenia:

➢ Attention deficits are recognized in patients with schizophrenia

➢ Since the dorsal visual stream serves areas of the parietal lobe important in attention it has
been hypothesized that a defect in this system may underlie attention deficits in this
population
➢ Reduced activation of precuneus and inferior parietal lobule was also found in this
population and found to correlate with violence
➢ Episodic memory loss was found to be associated with precuneus atrophy.
Gerstmann Syndrome:

➢ Pantomime recognition (recognition of common gestures) may be lost following damage to

the dominant inferior parietal lobule
➢ A lesion involving the angular gyrus may produce part or all of Gerstmann syndrome:
5. Left–right confusion

6. Finger agnosia

7. Dysgraphia

8. Dyscalculia

Balint Syndrome:

➢ The patient with Balint syndrome is unable to process the visual field as a whole and is fixed
on only one part, a form of tunnel vision known as simultanagnosia
➢ Bilateral damage to the posterior inferior parietal lobule, often including adjacent occipital
cortex, may produce Balint syndrome
4. Optic apraxia –eyes tend to remain fixed on a visual target, although spontaneous eye
movements are unaffected
5. Optic ataxia –a deficit in using visual guidance to grasp an object

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 6. Simultanagnosia –seeing only the components of a visual object; unable to see the
object as a whole
Tests for Parietal Lobe Function:

9. Object recognition

10. Eye movements

11. Calculations, reading and writing comprehension

12. Stereognosis, graphaesthesia

13. Gnosis and right-left confusion (by testing parts of body)

14. Praxis(ideational and ideomotor),truncal and limb apraxias-Eg:standing like a boxer,light a

candle

15. Picture description and construction of figures, Block design tests

16. Assessment of general sensations

References:

1)Georg Goldenberg:Apraxia and the parietal Lobes: Neuropsychologia 47 (2009) 1449–1459

2)Clark,Boutros and Mendez:The Brain and Behaviour:An introduction to Behavioural

Neuroanatomy:3rd edtn(1998)

3)Strub & Black:Mental Status Examination in Neurology:4th edtn(2000)

214
 Pineal Gland

Introduction:

➢ Located in the epithalamus near the centre of the brain, in a groove where the two halves of
the thalamus join, the pineal gland derives its name from the pinecone, which it resembles
in shape
➢ It is the only unpaired midline brain structure, reddish grey in colour
Location:

➢ It is a part of the epithalamus, lying between the thalamic bodies and posterior to the
habenular commissure. Lies in the quadrigeminal cistern near the corpora quadrigemina
➢ It lies behind the third ventricle and is bathed by CSF through the pineal recess of the third
ventricle projecting into the stalk of the gland
Blood supply:

➢ It lies outside the blood-brain barrier and has a rich blood flow,second only to the kidneys
➢ It gets its blood supply from the postyerior choroidal branches of the posterior cerbral
artery.
➢ Venous Drainage:
Drainage is into the straight sinus through short-course veins emptying into the internal cerebral
veins and basal veins of Rosenthal, which form the great cerebral vein of Galen.
Innervation:

➢ The pineal gland receives a sympathetic innervation from the superior cervicalganglion
➢ A parasympathetic innervation from the pterygopalatine and otic ganglia is also present
➢ Further, some nerve fibers penetrate into the pineal gland via the pineal stalk (central
innervation)
➢ Also, neurons in the trigeminal ganglion innervate the gland with nerve fibers containing the
neuropeptide PACAP (Pituitary adenylate cyclase activating peptide)
Microscopic Structure:

➢ Pineal cells and neuroglial cells (which support the pineal cells) mainly comprise the gland
➢ Four main types of cells have been identified:
1. Pinealocytes
2. Interstitial cells/glial cells
3. Perivascular phagocytes
4. Peptidergic neuron-like cells
➢ It also contains some calcium and phosphorus rich structures called corpora arenacea, which
have been linked with ageing
➢ Calcification density detected by computed tomography can be used to estimate the size of
functional tissue, which has been reported to be negatively correlated with age and with the
incidence of chronic daytime sleepiness and self-reported sleep disturbances

215
Development:

The gland grows in size until about 1–2 years of age, remaining thereafter its size does not vary
significantly, although its weight increases gradually from puberty. Abundant melatonin levels in
children are believed to inhibit sexual development, and pineal tumours have been linked with
precocious puberty. Melatonin production is reduced after puberty, though it continues to function
throughout life.

Functions:

➢ French philosopher and mathematician René Descartes was fascinated with the pineal gland.
He even regarded it as the “principal seat of the soul, and the place in which all our thoughts
are formed.”
➢ The gland secretes melatonin which has been found to play the following roles:
Circadian Rhythm:

➢ Melatonin secretion is rhythmic in nature, with high levels occurring in the night and low
levels during the day. This rhythm persists even when animals or human beings are housed
in constant environmental conditions (e.g. continuous darkness) suggesting thereby that the
rhythm is largely endogenous in nature
➢ The suprachiasmatic nucleus, the "master circadian clock", present in the hypothalamus, is
largely responsible for this endogenous melatonin rhythm
➢ It controls the activity of the pineal gland through the release of norepinephrine from the
sympathetic nerve fibres, with increased secretion at night
➢ It is believed to promote agent, and its synthetic analogue Agomelatine is used to treat shift-
related sleep disorders and to promote sleep
Action on mood:

➢ This hormone acts mainly on mid brain

➢ Hypothalamus and supra chiasmatic nucleus, although other areas like hippocampus and
substantia nigra have also been implicated
➢ Melatonin increases the concentration of biogenic amines like serotonin and catecholamines
in these areas of the brain and is thus believed to indirectly regulate mood through sleep
➢ Its use as an agent for mood disorders are being studied
Role on puberty:

➢ Onset of puberty has been attributed to the pulsatile secretion of gonadotrophin releasing
hormone (GnRH) by the arcuate nucleus of the hypothalamus
➢ Melatonin appears to have a direct and continuous regulatory action on gonadotrophin
secretory pattern from infancy to the onset of puberty
Role in stress:

➢ Melatonin has been found to be antistressogenic in nature and it participates in the overall
neuroendocrine mechanism involving hypothalamo-hypophyseal-adrenal system.

216
Psychiatric Implications:

1. Several studies have reported low nocturnal melatonin levels in depression, as well as in
dysthymia
2. Photoperiodic dysregulation in Seasonal Affective Disorder patients is more likely to be
associated with the phase of the melatonin rhythm relative to the day–night cycle, indicated
by higher therapeutic responses to bright light exposure in the morning than in the evening
3. Decreased melatonin production has also been documented in Fibromyalgia, known to
present with neuro-vegetative symptoms
4. Pathological changes in biological rhythms, including the melatonin rhythm, have been
hypothesized in chronic schizophrenia, possibly related to a stress-induced degeneration of
the hypothalamic–pituitary–adrenal (HPA) axis
5. Patients with alcohol-induced CNS damage and Wernicke-Korsakov Syndrome blunted
nocturnal melatonin levels, suggesting its levels to be affected by cerebrovascular events
6. There are some indications of involvement of pineal melatonin in the progression of senile
dementia, particularly of the Alzheimer’s type, and of a possible therapeutic role of
melatonin replacement
Conclusions:

➢ A great deal about the function of the pineal gland is still being studied, results until now
have showed a significant impact on mental health and illnesses, with hope of being used in
the treatment of such conditions in future

217
References:

1)V Srinivasan:THE PINEAL GLAND: ITS PHYSIOLOGICAL AND PHARMACOLOGICAL ROLE:Ind. J.

Physiol. Pharmac., Volume 33, Number 4, 1989 review article

2)M. Mila Macchi , Jevrey N. Bruce:Human pineal physiology and functional signiWcance of
melatonin:Frontiers in Neuroendocrinology 25 (2004) 177–195

3)D. Kunz, F. Bes, P. Schlattann, W.M. Herrmann, On pineal calciWcation and its relation to
subjective sleep perception: a hypothesis driven study, Psychiatry Res. 82 (1998) 187–191.

4)D. Kunz, S. Schmitz, R. Mahlberg, A. Mohr, C. Stöter, K.-J. Wolf, W.M. Herrmann, A new concept for
melatonin deWcit: on pineal calciWcation and melatonin excretion, Neuropsychopharmacology 21
(1999) 765–772

218
NEURO-
CHEMISTRY

219
 Monoamine Neurotransmitters

1. Acetylcholine:

Introduction
➢ First neurotransmitter to be discovered
➢ Synaptic transmission in both central and peripheral nervous system
➢ Initially called as the ‘vagal substance’ when it was discovered by the
stimulation of vagal nerve – later identified to be Ach.

Biosynthesis and Degradation

➢ Acetylcholine is synthesized from acetyl CoA and choline by an enzyme
called Choline acetyltransferase (ChAT)
➢ The acetyl CoA derives from pyruvate generated by glucose metabolism in
the mitochondria.
➢ Choline is obtained from dietary sources and from phosphatidylcholine.
➢ The transport of choline from the extracellular space into the neuron is done
by the sodium-dependent high-affinity choline uptake system. This system is
selectively inhibited by hemicholinium.
➢ The production of Ach takes place in the cytoplasm of cholinergic neurons
and stored at the nerve terminals of cholinergic fibres in vesicles.
➢ When an action potential reaches the neuron, ACh is released into the
synaptic cleft by exocytosis – further diffuses into postsynaptic site. Botulinum
and Tetanus toxins inhibit the release of ACh while the black widow toxin
enhances the release of ACh.
➢ 2 types of esterases metabolize ACh – Acetylcholine esterase and
Butyrylcholine esterase (pseudocholine esterase).
➢ ACh expressed in neurons, muscle cells and certain hematopoetic cells.
➢ The different forms of acetylcholine esterases are transported by active
neuronal transport mechanisms in retrograde and anterograde fashion.
➢ The primary blockers of AChE are:
o The carbamyl esters employed as adjuncts to anaesthetics,
o Organophosphates used as insecticides, and
Anticholinesterases like sarin which have been used as “nerve gas”.
These substances compete with acetylcholine and bind to the acetylcholine esterase.

RECEPTORS:
➢ The ACh receptors consist of - the muscarinic and the nicotinic receptors
➢ They can be distinguished by their selectivity to the alkaloids - nicotine
and muscarine

The Nicotinic receptors:

➢ Ligand-gated ion channel
➢ Activated by nicotine and inhibited by curare

220
 ➢ Two subclasses: a neuronal type and a muscle type
➢ The receptor constitutes of a complex of four distinct protein subunits, which
were classified in order of their molecular size (alpha= 40 kDA, beta= 50 kDA,
delta= 60 kDA, gamma= 65 kDA). The arrangement of the subunits consists
of a pentameric complex of the 2 alpha, beta, gamma and delta, which
encompass the ion channel
➢ Binding of 2 molecules of acetylcholine to the alpha-subunit induces a change
in the conformation of the pentamer and allows the influx of ions
➢ This influx results in a depolarization of the neuron
➢ No second messengers are involved in the signal transduction
➢ Nicotinergic receptors are present in the hippocampus, the cerebral cortex,
the thalamus, the hypothalamus, the superior colliculus as well as in some
cholinergic nuclei of the forebrain and brain stem
➢ Via nicotinic hetero-receptors, acetylcholine increases the level of glutamate,
serotonin, GABA or dopamine
➢ Acetylcholine also increases acetylcholine levels via nicotinic autoreceptors
The muscarinic receptors:

➢ The muscarinic receptors are metabotropic receptors, they belong to the

superfamily of G protein coupled receptors.
➢ They have seven membrane-spanning domains, the N-terminus residing on
the extracellular side and the C-terminus on the intracellular side.
➢ The muscarinic receptors have been divided into two classes, which are
designated M1 and M2, corresponding to their different selectivity to the
antagonists pirenzepine (M1) and gallamine (M2).
➢ The five subtypes are m1, m2, m3, m4 and m5.
➢ The two main pathways of signal transduction are: inhibition of adenylate
cyclase activity with subsequent reduction of intracellular cAMP levels;
activation of phosphatidyl inositol to form diacylglycerol and inositol
trisphosphate.
➢ M1 receptors are preferentially expressed in the cortex, the hippocampus, the
nucleus accumbens, the striatum and the amygdala
➢ Type M2 receptors occur in cholinergic nuclei of the thalamus as well as in
the superior colliculus, olfactory bulb and in the brain stem
➢ M3 are found in the hippocampus and in the cerebral cortex.

Biological Effects:
➢ Effects which are mediated through nicotinic receptor are rare in the
central nervous system
➢ The nicotinic receptors are considered to be involved in synaptic plasticity,
which uses calcium as a second messenger.
➢ Muscarinic acetylcholine receptors participate in parasympathic effects,
which include such principal physiological features as a decrease in heart
rate, smooth muscle contraction and blood vessel dilation.
➢ Muscarinic effects have been described in several brain areas: these
include the cerebral cortex, the locus coeruleus and some thalamic nuclei,
effects of which are predominantly excitatory in nature.

221
 ➢ In the central nervous system, acetylcholine is involved in the control of
certain motor activities and in processes coupled to learning and memory

Relevance to Neuropsychiatry:

1. Alzheimers disease:
A dysfunction of the cholinergic system occurs in some degenerative diseases of the brain,
like Alzheimer’s disease
The progression of Alzheimer’s disease is accompanied by reduction in the activity of
acetylcholine esterase in several cerebral structures, reduction in the biosynthesis of
acetylcholine, reduction in the high-affinity uptake of choline, loss of cholinergic neurons in
the nucleus basalis of Meynert and loss of nicotinic receptors in the cortex and in the
hippocampus.
2. In Parkinson’s disease: hyperactivity of cholinergic interneurons in the striatum, following
the reduction of the dopaminergic influence.

3. Huntington’s chorea: characteristic loss of cholinergic interneurons in the striatum.

4. Myastenia gravis:

➢ It an autoimmune disease which manifests itself at the motor endplate

➢ Autoantibodies directed to the nicotinic receptors of motor endplates produce a
masking of the receptors, which finally leads to their degradation.

Cholinergic distribution in brain

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 Nicotinic receptor

Ref: Oliver von Bohlen und Halbach and Rolf Dermietzel- Neurotransmitters and
Neuromodulators- Handbook of Receptors and Biological Effects-2nd edition.

Figures:

Slide no 1 - Distribution of ACh

Slide no 2 – Structure of nicotinic receptor

223
 Describe anatomy of monoamine neurotransmitter system

Introduction:
All monoaminergic systems share common anatomical features.
Each system constitutes:
o A cluster of cell bodies in a few restricted subcortical or brainstem regions
o Long and extensively branched axonal processes
o Multiple cortical and limbic target regions

Development of Monoamine Systems:

➢ A specific cascade of transcription factors including the ETS-domain factor
pet-1 specifies the neural cell fate of serotonergic neurons.
➢ The noradrenergic neuron formation depends upon secreted factors such as
bone morphogenic proteins (BMPs)
➢ Much less is known about the development of the histaminergic neurons of
the tuberomammillary nucleus.
➢ Once released, monoamines act on target cells by binding to specific cell
surface receptors. There are multiple receptor subtypes for each monoamine,
which are expressed in diverse regions and subcellular locales and which
engage a variety of intracellular signalling pathways. The same molecule may
activate some cells while inhibiting others, depending on which receptor
subtype is expressed by each cell

SEROTONIN:
➢ The cell bodies of serotonergic neurons are clustered in the midline raphe
nuclei of the brainstem
➢ The rostral raphe nuclei send ascending axonal projections throughout
the brain, while the descending caudal raphe nuclei send projections into
the medulla, cerebellum, and spinal cord
➢ The descending serotonergic fibers that innervate the dorsal horn of the
spinal cord have been implicated in the suppression of nociceptive
pathways
➢ Most serotonergic innervation of the cortex and limbic system arises from
the dorsal and median raphe nuclei in the midbrain; the serotonergic
neurons in these areas send projections through the medial forebrain
bundle into target forebrain regions
➢ The median raphe provides most of the serotonergic fibers that innervate
the limbic system, while the dorsal raphe nucleus provides most of the
serotonergic fibers that innervate the striatum and thalamus
➢ Dorsal raphe serotonergic fibers are fine, with small vesicle-coated
swellings called varicosities, while median raphe fibers have large
spherical or beaded varicosities

224
DOPAMINE:
➢ Dopamine neurons are more widely distributed in the CNS, residing in the
midbrain substantia nigra, ventral tegmental area, periaqueductal gray matter,
hypothalamus, olfactory bulb, and retina
➢ In the periphery, dopamine is found in the kidney where it functions to
produce renal vasodilation, diuresis, and natriuresis.
➢ The nigrostriatal, mesocorticolimbic and tuberohypophyseal system are
important in psychiatry.
➢ Nigrostriatal: Dopamine cell bodies in the pars compacta of the substantia
nigra send ascending projections to the dorsal striatum and modulate motor
control. Blockade of these by antipsychotics cause EPS.
➢ Mesocorticolimbic: The midbrain VTA contains dopaminergic neurons that
give rise to the mesocorticolimbic system which send ascending projections
that innervate limbic structures, such as the nucleus accumbens and
amygdala –the neural representation of reward, important in addiction.
Blockade of these receptors by antipsychotics are known to reduce the
positive symptoms of schizophrenia.
➢ Tuberohypophyseal system: consists of dopamine neurons in the
hypothalamic arcuate and paraventricular nuclei that project to the pituitary
gland, inhibit prolactin release. Antipsychotic drugs that block dopamine
receptors in the pituitary may thus disinhibit prolactin release and cause
galactorrhoea

225
NOREPINEPHRINE:

➢ Norepinephrine is released by the postganglionic sympathetic neurons of the

ANS.
➢ Widespread peripheral effects including tachycardia and elevated blood
pressure.
➢ Norepinephrine-producing neurons are found within the brain in the pons and
medulla in two major clusterings:
➢ The locus ceruleus (LC)
➢ Lateral tegmental noradrenergic nuclei.
➢ Noradrenergic projections from both of these regions ramify extensively.
➢ The activity of LC neurons varies with the animal’s level of wakefulness.
Firing rates are responsive to novel and/or stressful stimuli. Also has a role in
the regulation of arousal state, vigilance, and stress response.
➢ Regions such as the hypothalamus and lower brainstem, receive adrenergic
inputs predominantly from the lateral tegmental nucleus

HISTAMINE:
➢ Central histaminergic neural pathways have been characterized by
immunocytochemistry using antibodies to the synthetic enzyme histidine
decarboxylase and to histamine.
➢ Histaminergic cell bodies are located within a region of the posterior
hypothalamus termed the tuberomammillary nucleus.

226
 ➢ The activity of tuberomammillary neurons is characterized by firing that varies
across the sleep–wake cycle, with the highest activity during the waking state,
slowed firing during slow-wave sleep, and absence of firing during REM
sleep.
➢ Histaminergic fibers project diffusely throughout the brain and spinal cord.
➢ Ventral ascending projections course through the medial forebrain bundle and
then innervate the hypothalamus, diagonal band, septum, and olfactory bulb.
➢ Dorsal ascending projections innervate the thalamus, hippocampus,
amygdala, and rostral forebrain.

ACETYLCHOLINE:
➢ Two large clusters of cholinergic projection neurons are found within the
brain: The basal forebrain complex and the mesopontine complex.
➢ The basal forebrain complex provides the vast majority of the cholinergic
innervation to the non-striatal telencephalon. It consists of cholinergic neurons
within the nucleus basalis of Meynert, the horizontal and vertical diagonal
band of Broca, and the medial septal nucleus.
➢ The mesopontine complex consists of cholinergic neurons within the
pedunculopontine and laterodorsal tegmental nuclei of the midbrain and pons
and provides cholinergic innervation to the thalamus and midbrain areas and
descending innervation to other brainstem regions such as the LC, dorsal
raphe, and cranial nerve nuclei.

227
Ref: Kaplan’s textbook of Psychiatry

228
 Describe the neural pathways, synthesis and metabolism of Dopamine with
appropriate diagrams / Dopaminergic pathways in the brain (with appropriate
diagrams)

Introduction:
➢ Dopamine, earlier thought as just a precursor of norepinephrine, later gained importance
as a prominent neurotransmitter in the CNS, and has been found to be enriched in the
substantia nigra and in the striatum where the norepinephrine is absent.
➢ It was also found to occur in the peripheral nerves later.
➢ The dopaminergic system comprises three classes of neurons based on the length of
their projections:
1. The class with ultra-short projections: This includes amacrine-like neurons in
the retina and the periglomerular cells of the olfactory bulb.
2. The class with short projections: This class comprises three different
subsystems:
▪ Neurons which are located in the arcuate nucleus of the hypothalamus
(area A12).
▪ The intradiencephalic dopaminergic neurons
▪ Dopaminergic neurons located in the nucleus of the tractus solitaries and
in the periaqueductal gray.
3. The class with long projections: This class consists of neurons with very long
dopaminergic projections. The projections arise either in the retrorubal field (A8), in the
substantia nigra (A9) or in the ventral tegmental area. From these areas, they project on to 3
different brain areas forming 3 important tracts, viz –
▪ To the neostriatum - the nigrostriatal pathway
▪ To the limbic cortex – the mesocortical pathway
▪ To the additional limbic structures – the mesolimbic pathway.

Biosynthesis and Degradation:

➢ The biosynthesis of dopamine takes place within nerve terminals
➢ Dopamine is synthesized from tyrosine in a two-step process.
➢ The first step is catalysed by tyrosine hydroxylase and results in the
production of dihydroxyphenylalanine
➢ Tyrosine hydroxylase requires tetrahydrobiopterin and oxygen as co- factors
and forms the rate-limiting step of dopamine synthesis.
➢ The catalytic product of tyrosine is L-DOPA, which is then decarboxylated to
dopamine by the cytosolic DOPA decarboxylase.
➢ Dopamine is transported through a specific transport system into presynaptic
vesicles
➢ Dopamine is released by action potentials through a calcium-dependent
mechanism into the synaptic cleft

229
 The calcium influx through voltage-dependent calcium channels

Fusion of the vesicle with the presynaptic membrane

Pore formation

Dopamine released into the synaptic cleft

Dopamine then binds to postsynaptic receptors

This binding induces a change in the conformation of the receptors

Triggers the membrane permeability for ions and initiates a complex chain of intracellular
postsynaptic events

➢ The outcome is an activation or inhibition of the postsynaptic neuron

➢ The removal of dopamine from the synaptic cleft involves specific re-uptake
mechanisms into the presynaptic terminal where it can be stored and reused
➢ Specific dopamine transporters (DAT) support the re-uptake
➢ The dopamine transporter is a glycoprotein of 619 amino acids (70 k Da) which
shows a 12-span trans-membranous motif
➢ The uptake process depends on Na+ and Cl–.
➢ The transporter is very efficient and about 80% of the released dopamine is
recaptured by this re-uptake mechanism
➢ In addition, the presynaptic membrane contains some dopamine receptors called
autoreceptors
➢ A blockade of these receptors facilitates the synthesis and presynaptic release of
dopamine, while their stimulation has the opposite effect
➢ Dopamine can be degraded by the activity of monoamine oxidase (MAO) and
aldehyde dehydrogenase or alternatively by catechol-O-methyltransferase
(COMT) to form dihydroxyphenylacetic acid (DOPAC) and 3-methoxytryptamine
(3-MT) respectively
➢ DOPAC and 3-MT are then further degraded to form homovanillic acid (HVA)

230
 Synthesis of dopamine

Degradation of dopamine

231
Dopamine receptors:

- Autoreceptors:
➢ The presynaptic autoreceptors play a significant role in modulating and
monitoring the release and synthesis of dopamine
➢ Stimulation of autoreceptors located at the nerve terminals results in an
inhibition of dopamine release and synthesis, whereas stimulation of
somatodendritic autoreceptors decreases the firing rate of the
dopaminergic neurons.

- The dopaminergic receptors are divided into the D1 and D2 groups.

➢ The D1 group consists of D1 and D5 receptors, which are positively linked
to adenylate cyclase
➢ The D2 group consists of D2, D3 and D4 receptors and each of these
receptor types exists in different isoforms. The dopaminergic
autoreceptors belonged to the family of D2 receptors.

D1 family
D1 and D5
In the striatum, amygdala, thalamus,
mesencephalon, hypothalamus and
the hindbrain.
A very short third intracellular loop
and a long C-terminal tail
Stimulate the activity of the adenylate
cyclase
Genes located on chromosomes 5
and 4
D2 family
D2, D3, D4
In the striatum,mesencephalon,
spinal cord, hypothalamus and
hippocampus.
a long third cytoplasmic loop and
a short C-terminal tail
inhibit adenylate cyclase activity
Genes located on chr 11 and 3

Biological Effects:
➢ Dopamine is involved in diverse functions like the modulation of arterial blood-
flow, higher brain functions like cognition and learning and in anxiety-related
behaviour.
➢ The nigro-striatal system is concerned with the initiation and maintenance of
motor behavior.
➢ The mesolimbic and mesocortical systems appear to be involved in goal-
directed and reward-mediated behavior and in motivation-dependent
behavior.
➢ The tuberoinfundibular system plays a major role in the regulation of pituitary
and hypothalamic peptides. An increase in dopamine activity in this system
results in an inhibition of prolactin release. Thus, dopamine constitutes the
prolactin- inhibiting factor.
➢ Arterial blood-flow regulation, feeding, as well as drinking activities initiated by
the ventromedial and lateral hypothalamic nuclei are also modulated by
dopamine
Ref: Oliver von Bohlen und Halbach and Rolf Dermietzel- Neurotransmitters and
Neuromodulators- Handbook of Receptors and Biological Effects-2nd edition

232
 Serotonergic pathways in the brain / Write in detail about serotonin
Neurotransmission

Introduction:

➢ Serotonin which was discovered as a substance mediating vasoconstriction

derives its name from serum (because the substance can be found in blood
serum) and tonic (because it provides vasotonic properties).
➢ Belongs to the class of biogenic amines.
➢ Predominantly found in the nucei of raphe - a relatively high density of
serotonergic projections occurs in the cerebral cortex, the hippocampus, the
amygdala, the basal ganglia, the lateral geniculate nucleus, the
suprachiasmatic nucleus, the tectum opticum, the substantia gelatinosa and
in the ventral horn of the spinal cord

Biosynthesis and Degradation:

➢ The precursor of serotonin is the essential amino acid tryptophan.
➢ The availability of tryptophan represents the rate-limiting factor in the
synthesis of serotonin. The synthesis of serotonin ceases when the
intracellular tryptophan stores have been depleted and the initial enzyme in
tryptophan synthesis (tryptophan hydroxylase) becomes deprived of its
substrate.
➢ L-Tryptophan combines with O2 in the presence of Tryphtophan hydroxylase
enzyme to form L-5-hydroxytryptophan, which in turn forms 5-
hydroxytryptamine through decarboxylation.
➢ Inactivation of serotonin takes place by a specific re-uptake mechanism.
➢ The serotonin transporter (Sert) depends on the electrochemical gradient of
Na+ and K+ and is an important pharmacological target for antidepressants.
➢ Its enzymatic degradation is by monoaminooxidase A (MAO-A) and an
aldehyde dehydrogenase. The resulting metabolite, 5-hydroxyindolic acid (5-
HIAA), is eliminated via the urinary tract.

233
Receptors:
➢ The quaternary structure of 5-HT receptors consists of at least three different
constituents: the transporter, the ligand-gated ion channel and the G protein-
coupled receptor, the largest group belonging to the superfamily of G protein-
coupled receptors as shown in the below table.
➢ Seven subtypes of 5-HT receptors have been distinguished (5-HT1 to 5-HT7) on
the basis of cloning data, with sub-groups in each type.

Subtype of the 5-HT receptors

G-Protein coupled receptors-
1. 5-HT1 family 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F
2. 5-HT2 family 5-HT2A, 5-HT2B, 5-HT2C
3. Others 5-HT4S,5-HT4L, 5-HT5A, 5-HT5B, 5-HT6, 5-HT7
Ligand-gated ion channels 5-HT3
Transporters 5-HT “uptake site”

➢ The 5-HT1A receptors, which constitute autoreceptors, are preferentially

expressed on the soma and dendrites of serotonergic neurons
➢ Their activation inhibits the firing rate of serotonergic fibers and their
desensitization after long term exposure to 5-HT uptake blocker restores the
firing rate.
➢ The 5HT1B receptor subtype is concentrated in the basal ganglia, striatum
and frontal cortex. The receptor is negatively coupled to adenylyl cyclase.
➢ The receptor subtype 5-HT1D shows autoreceptive function in humans.
➢ The 5-HT1E and 5-HT1F are negatively linked to adenylyl cyclase

234
 ➢ The 5-HT2 receptors: mediate slow excitatory effects through a decrease in
potassium conductance or, alternatively, an increase in non-selective cation
conductance.
➢ The 5-HT2 receptor subfamily consists of three members: 5-HT2A, 5-HT2B
and 5-HT2C.
➢ The 5-HT2 receptors are coupled to phospholipase C and binding of the
ligand leads to activation of phosphoinositol metabolism
➢ The 5-HT3 receptor type exhibits ionotropic features and belongs to the
superfamily of ligand-gated ion channels, hence structurally and functionally
different from the other serotonergic receptors.
➢ In contrast to the 5-HT1 and 5-HT2 receptors, which are located on neurons,
glia and muscle cells, the 5-HT3 receptors are exclusively expressed in
neurons.
➢ Signal transduction of the 5-HT4 receptors involves cAMP, which
distinguishes them from the other 5-HT receptors.
➢ Activation of 5-HT4 receptors in the hippocampus elicits an increase in
intracellular cAMP levels and a decrease in K+ conductance.
➢ 5HT5A and 5HT5B, both subtypes are G protein-coupled receptors with the
seven transmembrane-spanning model.
➢ The 5HT6 receptor is of seven transmembrane domains and is positively
coupled to adenylyl cyclase via G proteins.
➢ 5-HT7 is the most recent 5-HT receptor identified by molecular cloning,
expressed mainly in the central nervous system.

BIOLOGICAL EFFECTS:
➢ Serotonin influences processes related to memory and learning, sexual
behaviour and feeding
➢ 5-HT2 antagonist ketanserin inhibits salt appetite induced by sodium
depletion
➢ Serotonin seems also be involved in regulating aggressive behaviour.
➢ Serotonin plays a significant role in nociception within the CNS
➢ Serotonin receptors increase release of adrenocorticotrophin (ACTH) and
corticosterone
➢ It mediates corticotropin release from the hypothalamus. Both 5-HT1A and 5-
HT2 receptor subtypes are involved in the regulation of the secretion of
corticotrophin-releasing factors
➢ Serotonin-containing neurons also appear to influence the secretion of other
pituitary hormones, especially prolactin and gonadotropins

Ref: Oliver von Bohlen und Halbach and Rolf Dermietzel- Neurotransmitters and
Neuromodulators- Handbook of Receptors and Biological Effects-2nd edition

235
 Nor-adrenergic pathways in brain

Introduction:
➢ Norepinephrine belongs to the family of catecholamines which derive from the
same precursor molecule tyrosine.
➢ Consists of a benzene ring with two adjacent hydroxyl groups and an
ethylamine side-chain.
➢ Norepinephrine is the direct precursor of epinephrine also serves as an
independent neurotransmitter.
➢ Apart from the peripheral nervous system, norepinephrine is also a major
transmitter in the central nervous system.
➢ Noradrenergic cell somata are found in the locus coeruleus (LC) and locus
subcoeruleus (groups A5, A6, A7), as well as in some areas of the formatio
reticularis (groups A1 and C1) and in the nucleus of the tractus solitarius
(groups A2 and C2).
➢ The locus coeruleus is a major source which innervate the cerebral cortex,
the hippocampus, the amygdala, the septum, the thalamus, the hypothalamus
and the spinal cord.
➢ The medial part of the LC projects to the cortex, whereas the posterior
portions of the locus coeruleus project to the hippocampus.

Biosynthesis and degradation:

➢ In sympathetic neurons, the enzymes tyrosine hydroxylase, DOPA-
decarboxylase, dopamine-beta-hydroxylase and phenyl ethylamine-N-methyl-
transferase are expressed in the cell soma, from which they are transported
to the nerve terminals by the anterograde axoplasmic flow.
➢ The first step is hydroxylation of tyrosine to L-DOPA by tyrosine hydroxylase
which is the rate-limiting step.

Tyrosine hydroxylase requires tetrahydrobiopterin and oxygen as cofactors.

L-DOPA is then decarboxylated to dopamine by an aromatic acid decarboxylase.

In noradrenergic neurons, dopamine is converted to norepinephrine by the copper ion-

containing dopamine-beta-hydroxylase.

The cytosolic norepinephrine is subsequently imported through a specific vesicular transport

mechanism into synaptic vesicles.

In some neurons of the CNS and in chromaffin cells of the medulla of the adrenal gland,
norepinephrine is not released, but is further metabolized to generate epinephrine, catalyzed
by phenyl ethanolamine-N-methyltransferase.

➢ Excess of catecholamines inhibits the activity of tyrosine hydroxylase in a

negative feedback loop. Vasoactive intestinal peptide (VIP) or growth

236
 factors like the nerve growth factor (NGF) can upregulate tyrosine
hydroxylase activity.
➢ Inactivation of norepinephrine is mainly through its re-uptake from the
synaptic cleft. Norepinephrine transporters (NET) mediate the removal of
NE from the extracellular space, thereby limiting the extent of activation of
auto and hetero adrenoceptors.
➢ The activity of norepinephrine transporters depends on the
transmembrane Na+ gradient.
➢ Norepinephrine, like other catecholamines, is metabolized by cytoplasmic
catechol-O-methyl-transferase (COMT) or by intra-mitochondrial
monoamine oxidase (MAO).
➢ The monoamine oxidase converts epinephrine and norepinephrine to 3,4-
dihydroxymandelic acid.

RECEPTORS:
➢ The three different types of norepinephrine receptors are alpha 1, alpha 2
and beta
➢ All three adrenoreceptor types have in common the property that they
couple to G proteins and show the topology of the seven membrane-
spanning domain model
➢ Three different subtypes of the alpha-1 receptors (alpha-1A, alpha-1B and
alpha-1D) have been identified, as well as three different subtypes of
alpha-2 receptors (alpha-2A, alpha-2B and alpha-2C)
➢ Three further subtypes of beta receptors (beta1, beta2 and beta3) are
noted

237
 Subfamily G-pr Second Agonists Antagonists Cloned
coupling Messenger subtypes
Alpha 1 Gq Ca2+ Phenylephrine Prazosin 1A,
Methoxamine WB 4101 1B,1D
Alpha 2 Gi Camp Clonidine Rauwolsin 2A,
Dexmedetomidine Yohimbine 2B,2C
Beta Gs Camp Isoproterenol Propranolol 1,2,3
Terbutalin Metaprolol

➢ The Alpha-1A receptors are most sensitive to the alpha-1-specific antagonist

WB4101 and are insensitive to chloroethylclonidine
➢ In contrast, the alpha-1B receptors exhibit low affinity for WB4101 and they
are sensitive to chloroethylclonidine inactivation
➢ Linkage of the Gq protein to the alpha 1 receptors results in the activation of
phospholipase C, which initiates the generation of 1,4,5-trisphosphate (IP3)
and diacylglycerol (DAG)
➢ The alpha 2C is coupled to a pertussis toxin-sensitive inhibitory G protein (Gi)
➢ While the alpha-2B is linked to a pertussis toxin-insensitive G protein and is
capable of activating adenylate cyclase, the alpha-2A receptor inhibits
adenylate cyclase at low agonist concentrations and shows a reverse effect at
high concentrations
➢ The alpha-2 receptor family has been found primarily on presynaptic
membranes, whereas the alpha-1 receptors occur at postsynaptic sites
➢ The beta1 receptors are expressed primarily in neurons, whereas the beta2
receptors are found in glia
➢ All three subtypes of beta adrenoceptors are coupled to Gs proteins, which
leads to a stimulation of adenylate cyclase activity
➢ A prolonged exposure of the beta adrenoceptors to their agonists reduces the
responsiveness of the receptors (desensitization)

BIOLOGICAL EFFECTS:
➢ The functional consequences of noradrenergic receptor activation can be
either inhibitory or excitatory
➢ Electrical stimulation of the locus coeruleus induces a decrease in the
spontaneous activity of the neurons
➢ On the other hand, norepinephrine seems to potentiate the neuronal
responses to visual, auditory or nociceptive stimuli
➢ NPY and norepinephrine are co-released and act synergistically on
vasoconstriction.
➢ In peripheral tissues, activation of alpha1 adrenoceptors causes
vasoconstriction, enhances glycogenolysis and more generally induces the
contraction of smooth muscle cells, whereas activation of beta adrenoceptors
leads to vasodilatation, bronchodilation and positive ionotropic and
chronotropic effects on heart tissue.
➢ Neuronal activation of beta adrenoceptors is responsible for
hyperpolarization, which depends on the activation of cAMP, accompanied by
an increase in membrane resistance.

238
 ➢ The regulation of general attention and circadian rhythm is of interest and its
response to stress-induced stimuli are the major functions served in the CNS.

Ref: Oliver von Bohlen und Halbach and Rolf Dermietzel- Neurotransmitters and
Neuromodulators- Handbook of Receptors and Biological Effects-2nd edition

239
 Amino acid Neurotransmitters

Describe the glutamate receptors. Add a note on drugs which act on these receptors/
Glutamate / Role of CNS glutamate in psychiatry / NMDA receptors

Introduction:
➢ Most important excitatory neurotransmitter of the CNS.
➢ The amino acid transmitters like glutamate and glycine are not only
neurotransmitters but also universal cellular constituents.
➢ Is a non-essential amino acid as it can be synthesized in the neurons.
➢ Glutamatergic neurons are mainly present in the cerebral cortex and project
to a variety of subcortical structures like hippocampus, the basolateral
complex of the amygdala, the substantia nigra, the nucleus accumbens, the
superior colliculus, the caudate nucleus, the red nucleus and the pons.

Biosynthesis and degradation:

➢ Glutamate is produced from alpha-ketoglutarate, an intermediate in the
tricarboxylic acid cycle of intermediary metabolism i.e. the Krebs cycle by the
activity of glutamate dehydrogenase or by transamination of alpha-
ketoglutarate
➢ After it is released, glutamate is taken up from the synaptic cleft by specific
transporters in the membrane of both neurons and glia
➢ The glutamate taken up by astrocytes is converted to glutamine by the
enzyme glutamine synthase
➢ This glutamine then diffuses back into particular neurons where it is
hydrolysed back to glutamate
➢ Phosphate-activated glutaminase (PAG), which is present at high
concentrations in such neurons, is responsible for salvaging the molecule for
reuse as a transmitter

Transporters:
➢ A family of four different members of the excitatory amino acid transporters
(EAAT) has been identified in glutamate transport: EAAT1-4, EAAT-1, EAAT2
and EAAT3.
➢ All four types of glutamate transporters are expressed in the brain but are
distributed differentially: EAAT1 and EAAT2 transporters appear to occur
exclusively in glia, whereas EAAT3 seems to be the neuronal transporter.
➢ The cellular uptake of glutamate is driven by the electrochemical gradients of
Na+ and K+ and is accompanied by pH and voltage changes.
➢ The transporters terminate the excitatory signal and prevent excitotoxic
damage.
➢ They are also a prerequisite to the recycling of the transmitter.

240
Receptors:
➢ The excitatory amino acid receptors include ionotropic (ligand-gated ion
channels) and metabotropic (receptors involving second messenger systems)
receptor subtypes.
➢ The ionotropic receptors are further classified as NMDA, AMPA and Kainate
receptors.

241
Receptor NMDA AMPA Kainate mGluR
Subtype
Selective NMDA AMPA Kainate Quisqualate,
agonists L-AP4

Functional Activation of Activation of Activation of Activation of

characteristics Na+, K+ and Na+ and K+ Na+and K+ phospholipase
Ca2+ channels channels channels C; inhibition of
adenylate
cyclase
Other agonists Ibotenate, Quisqualate, Domoat, Quisqualat,
quinolinate kainate, acromelic acids L-serine
domoate A and B O-phosphate,
ibotenat, CCG

➢ The ionotropic receptors include a glutamate-sensitive ion channel that opens

upon activation and allows the influx of Na+ and K+ and/or Ca2+, which
subsequently elicit fast excitatory responses, measurable in the form of excitatory
postsynaptic potentials (EPSP)
➢ The receptors which are activated by quisqualate belong to the group of
metabotropic receptors
➢ They involve second-messenger systems in signal transduction and they are
coupled to G proteins

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NMDA receptors:
➢ NMDA receptors are selectively activated by the drug NMDA and they are
less selectively activated by glutamate, aspartate or homocysteate (HC).
➢ The NMDA receptors respond in a relatively slow fashion. This slow
responsiveness is thought to be due to the fact that Mg2+ tonically inhibits
NMDA receptors.
➢ The topological model of the NMDA receptor consists of a complex of five
transmembrane proteins with different specific binding sites associated with
an ion channel which is permeable to Ca2+, Na+ and K+.
➢ The different binding sites of the NMDA receptors can be divided into four
➢ categories:
o A main binding site for agonists
o A ligand-gated ion channel which can be blocked at two specific sites
o Different regulatory binding sites such as an allosteric binding site for
glycine, a polyamine site as well as Mg2+ and Zn2+ selective sites
o These sites exert either negative or positive control over the function of
the NMDA receptors

Under resting potential conditions, the NMDA receptors are not activated and the ion
channel is blocked by Mg2+.

On depolarization, the magnesium block is released.

The channel opens, thereby allowing the exchange of ions through the channel pore.

Increases the permeability for Na+, K+ and Ca2+.

Entry of extracellular calcium through the channel activates variety of processes which alter
the properties of the neuron
➢ The NMDA receptors are heteromeric complexes, which consist of two different
subunits, NR1 and NR2
➢ The NR1 subunits form the molecular backbone of the receptor, while the subunit
NR2 is responsible for its physiological and pharmacological properties.

AMPA receptors:
➢ AMPA receptors are ionotropic receptors.
➢ They can be activated by the agonists AMPA, quisqualate and glutamate.
➢ The AMPA receptors are associated with a cation-selective ion channel which
is permeable to Na+ and K+, however it also becomes permeable to Ca2+
under some conditions.
➢ Four different subtypes of AMPA receptors are recognized namely GluR1,
GluR2, GluR3, GluR4.
➢ In addition, all subtypes can occur in two forms as a result of of alternative
splicing and they can be distinguished by the presence or absence of a
segment in the last transmembrane domain. These two splice variants are

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 named “flip” and “flop” and they have different effects on responses of the
channel.
➢ High densities of AMPA receptors have been identified in the neocortex, the
hippocampus, the lateral septum, the basolateral nucleus and the lateral
nucleus of the amygdala, the caudate-putamen, the nucleus accumbens,
bulbus olfactorius and in the molecular layers of the cerebellum.

Kainate receptors:
➢ Kainate receptors can be activated by kainate and glutamate.
➢ Like the AMPA receptors, the kainate receptors are associated with an ion
channel which is permeable for the monovalent cations Na+ and K+ and for
Ca2+.
➢ High-affinity kainate receptors are formed by different subunits, which belong
to two structural classes. The first class consists of GluR5, GluR6, GluR7 and
second class consists of KA-1 and KA-2.
➢ Kainate receptors have been found in the neocortex, the piriform cortex and
the hippocampal formation as well as in the caudate-putamen, the reticular
nucleus of the thalamus and in other brain areas.
➢ These receptors are probably involved in modulating the release of excitatory
amino acids and additional neurotransmitters or neuromodulators.

The metabotropic glutamate receptors:

➢ The metabotropic glutamate receptors are coupled to G proteins and the
signal transduction involves different second-messenger systems. They
generate slow postsynaptic responses.
➢ They interact with the adenylate cyclase system and the protein kinase C
system but can alternatively also activate the phospholipase C-DAG-IP3
pathway.
➢ The metabotropic receptors are activated by glutamate, quisqualate, ACPD or
L-serine-O-phosphate and ibotenic acid. However, they are resistant to
activation by NMDA, AMPA or kainite.
➢ Eight types of receptors have been identified and classified into three groups
based on their linkage to second-messenger systems and their
pharmacology- group I (mGluR1 and mGluR5) act via the phospholipase C
system whereas group II (mGluR2 and mGluR3) and group III (mGluR4,
mGluR6, mGluR7 and mGluR8) inhibit adenylate cyclase. Metabotropic
receptors of group II can be activated by CCG, whereas receptors of group III
bind the agonists L-serine-O-phosphate and 2-AP4.
➢ The metabotropic receptors contribute to delayed neuronal responses and to
synaptic plasticity. It is also believed that these receptors are involved in
processes coupled to LTP, learning and memory storage.

Biological Effects:
➢ Involved in fast synaptic transmission and long term potentiation.
➢ Neuroendocrine regulatory functions by influencing the secretion of pituitary
hormones, which play a role in the reproductive cycle;
➢ In neuronal migration during development.
➢ Involvement in the reception and processing of environmental stimuli and
motor behaviour.
➢ Also acts as a target site for various D-aminoacids.

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Neuropsychiatric aspects:
➢ “Excitotoxicity” involving sustained activation of glutamate receptors can be
observed as a pathophysiological mechanism in various condition like
ischemia, hypoglycemia, epileptic seizures and in neurodegenerative
diseases such as Alzheimer’s disease, Parkinsonism and Amyotropic lateral
sclerosis.
➢ The glycine modulatory site of the NMDA receptors is considered to
participate in the clinical manifestation of schizophrenia and is a theraupeutic
target. Clinical trials with NMDA receptor agonists (glycine, D-serine and D-
cycloserine) showed improvements in negative and cognitive symptoms of
schizophrenia.
➢ Stimulation may be beneficial in disorders associated with primary memory
deficits. Memantine, a weak NMDAR channel blocker, has shown safety and
efficacy in slowing the decline in moderate to advanced AD.
➢ Inhibition may exert positive effects in disorders with neurodegeneration.
Effects of glutamatergic agents have been studied more extensively with
regard to Alzheimer’s disease (AD), anxiety and posttraumatic stress disorder
(PTSD).
➢ Glutamatergic therapies are also tried in neuropathic pain. Here the NMDA
receptor and, in particular, glycine-site antagonists have shown promise.

Ref: Oliver von Bohlen und Halbach and Rolf Dermietzel- Neurotransmitters and
Neuromodulators- Handbook of Receptors and Biological Effects-2nd edition

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Describe the synthesis, metabolism, pathways and receptors of GABA / GABA / Synthesis
of GABA and GABA receptors

Introduction:
➢ GABA or gamma amino butyric acid is a small amino acid which forms the
principal inhibitory neurotransmitter in the central nervous system.
➢ Though initially thought to be present only in the inhibitory interneurons, later
GABAergic projection neurons were also discovered.
➢ High densities of GABAergic neurons are seen in the striatum (95%). The
other brain areas rich in GABAergic neurons are the globus pallidus, the
substantia nigra (pars reticularis) and the cerebellum
➢ GABAergic interneurons are most frequent in the thalamus, the hippocampus
and in the cerebral cortex

Biosynthesis and Degradation

➢ The most important step in synthesis of GABA is the decarboxylation of
glutamate by glutamic acid decarboxylase (GAD), in the presence of co-factor
pyridoxal phosphate (PLP, a form of vitamin B6).
➢ Glutamic acid decarboxylase exists in two different isoforms, GAD65 and
GAD67. Both these forms of GAD are expressed and regulated in different
ways and their individual roles remain unclear.
➢ GABA is inactivated by transamination with alpha-ketoglutarate. This reaction
is regulated by the enzyme GABA transaminase (GABA-T).
➢ In many inhibitory neurons, both GAD and GABA-T are co-expressed but,
unlike GAD, GABA-T is associated with mitochondria.

GABA transporters
➢ GABA transporters (GAT) are located in the plasma membrane and mediate
the removal of GABA from the extracellular space in order to terminate
synaptic events.
➢ GABA transporters exhibit 12 transmembrane-spanning segments.
➢ The uptake mechanism depends on Na+ and Cl–. One cycle of GABA
transport carries two Na+ ions from the extracellular space into the cell.A
reversal of the Na+ gradient gives rise to an inverse effect, by which GABA is
released from neurons and glia.

Receptors and Signal transduction

➢ GABA binds to its receptors and produces an increase in membrane
permeability to Cl– ions, which elicit a hyperpolarization of the postsynaptic
membrane.
➢ Three types of GABA receptors can be classified, GABA-A, GABA-B and
GABA-C receptors.

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 Receptor Ion Second Agonists Antagonists Modulators
channel messenger
gating
GABA-A Direct - GABA, Bicuculline, BZDs,
muscimol, picrotoxin, barbiturates,
3-APS TBPS steroids,
Zn2+,
PKA, PKC
GABA-B Indirect cAMP baclofen, CGP 36742, -
via G GABA CGP 54626,
protein CGP 55845
GABA-C Direct - GABA, Picrotoxin PKC
CACA,
CAMP

GABA-A receptors
➢ The GABA-A receptor is a hetero-oligomeric receptor and belongs to the
superfamily of ligand-gated ion channels. The GABA- A receptor consists of
different subunits, alpha, beta, gamma, delta, each of which encloses
different members.
➢ The most common model of the GABA-A receptor consists of a pentameric
structure, which forms an ion pore and is selective for Cl– .The pentameric
structure is composed of two alpha-subunits, one beta-subunit and one
gamma-subunit. The fifth unit in the pentamer is variable and can be provided
either by one of the alpha or gamma subunits or a delta subunit.
➢ The functional behavior of GABA-A receptors can also be influenced by
certain ions, like Zn2+, H+ and some polycations.
➢ The GABA-A receptor possesses three different binding sites. The first
binding site binds the neurotransmitter GABA. A second binding site on the
receptor is a specific binding site for benzodiazepines and a third binding site
is specific for barbiturates.

GABA-B receptors:
➢ GABA-B is a heterodimer of two subunits, GABA-B(1) and GABA-B(2).
➢ Belongs to the class of metabotropic receptors and thus is a member of
the superfamily of G protein-coupled receptors (GPCRs).
➢ Pre-synaptically located GABA-B receptors modulate neurotransmitter
release by depressing Ca2+ influx through voltage-activated Ca2+
channels of the N type.
➢ Both types of presynaptic GABA-B receptors are expressed: auto
receptors that control GABA release and heteroreceptors that inhibit all
other neurotransmitter release.

GABA-C receptors:
➢ This receptor is insensitive to bicuculline or baclofen.
➢ The GABA-C receptor is coupled to a Cl– selective ion channel.

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 ➢ They have been identified in the pituitary and in horizontal and bipolar
neurons of the retina.
➢ An allosteric modulation side for benzodiazepines or barbiturates is
absent
➢ Picrotoxin acts as an antagonist

Biological Effects:
➢ GABA mediates inhibitory effects on the postsynaptic membrane.
➢ The cell bodies of enteric neurons possess bicuculline-and picrotoxin-
sensitive GABA receptors, which mediate effects in the enteric system.
➢ GABA-A receptors being involved in memory storage and long-term
potentiation.
o The GABA-A receptor antagonists picrotoxin and bicuculline
enhance memory functions, whereas benzodiazepines and the
GABA-A agonist muscimol depress memory functions.
➢ Endogenous GABA binds to GABA-A receptors in the basolateral
amygdala and inhibits anxiety responses.
➢ Inhibitors of the GABA transporters, benzodiazepines and barbiturates,
which facilitate GABAergic transmission, show anticonvulsive properties.
➢ Baclofen which acts on GABA-B is used to treat spasticity and skeletal
muscle rigidity.
➢ Barbiturates which act on GABA-A are used therapeutically as sedatives
and hypnotics.
➢ The benzodiazepines show anticonvulsive, anxiolytic, sedative and
muscle-relaxant properties. They are also used for the treatment of
anxiety and sleep disorders.

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Ref : Oliver von Bohlen und Halbach and Rolf Dermietzel- Neurotransmitters and
Neuromodulators- Handbook of Receptors and Biological Effects-2nd edition

249
 Cannabinoid receptors

HISTORICAL ASPECTS:

➢ Chinese emperor: Shen Nung – First Medical use.

➢ India – used as appetite stimulant called ‘Munchies’.
➢ Delta tetrahydrocannabinol [THC] – was found to be the psychoactive component.
➢ Endogenous brain endocannabinoid found.
SYNTHESIS

➢ Synthesized from ARACHIDONIC ACID.

➢ It is not stored. It is synthesized as per requirement and released on neuronal
depolarisation with influx of Ca2+.
ENDOGENOUS CANNABINOID [EC]

1. Anandamide
2. N-Arachidonoyl Dopamine (NADA)
3. 2-arachidonoylglycerol (2-AG)
4. 2-arachidonoylglycerol ether (2-AGE)
5. Virodhamine
INACTIVATION

1.Reuptake

2.Enzymatic degradation

➢ Endocannabinoids are metabolized by intracellular enzymes.

➢ Anandamide is metabolized by fatty acid amide hydrolase (FAAH). FAAH is expressed
in the soma and dendrites of neurons.
➢ 2-ArachidonoylGlycerol is metabolized by monoacylglycerol lipase (MGL). MGL is
distributed in presynaptic terminals.
RECEPTORS

CB1 & CB2 are G protein coupled receptors.

CB1 – cortex,cerebellum,basal ganglia.
CB2 – WBC,immune system.

➢ Gs-stimulates adenyl cyclase.Gi/o – inhibits adenyl cyclase & other physpholipases.

➢ Endocannabinoid mediates short-Term Plasticity.
➢ They function as retrograde messengers at synapses in the CNS.

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CLINICAL USE

1) SCHIZOPHRENIA:
➢ Large doses of THC can cause psychotic symptoms in normal individuals.
➢ THC may worsen psychotic symptoms in Schizophrenic patients.
➢ THC decreases effectiveness of antipsychotic drugs.
➢ Use of cannabis may precipitate schizophrenia in susceptible individuals.
➢ Treatment with anti-psychotics appears to normalize imbalance in EC signaling in
blood cells of Schizophrenic patients.
➢ Cannabidiol has been shown to have anti-psychotic potent. E.C.S. may be a novel
therapeutic target in Schizophrenia.

2) MDD AND ANXIETY:

➢ Lower doses – calmness, anxiolytic effect & euphoria
➢ Higher doses – dysphoria & anxiety
➢ Lower doses of THC & CP 55940 – anxiolytic
➢ Pharmacological CB1 signaling by FAAH inhibitors may have therapeutic value in
anxiety disorders, OCD and depression

3) ADDICTION:
➢ Genetic vulnerability to addiction is linked to functional deficiency in the second order
neuron
➢ CB1 increases extra cellular dopamine in nucleus accumbens
➢ CB1 also increases firing rates of dopaminergic neurons

4)NEUROPROTECTIVE:

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 ➢ Endocannabinoids decreases brain edema, infarct size, cell death and improves
cognition.
5)ANALGESIA:
➢ CB1 receptor mediates analgesia through vanallid receptor.

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Cytochrome P450

History and Background:

• In 1955, Axelrod and Brodie et al., identified an enzyme system in the endoplasmic
reticulum of the liver which was able to oxidize xenobiotic compounds
• In 1964 this was named cytochrome P450 (CYP 450) after the strong feature in its
absorption spectrum.
• In 1985 a full structure of (CYP101), a bacterial P450 from Pseudomonas putida, was
obtained
• Cytochromes P450 have been named on the basis of their cellular (cyto) location and
spectrophotometric characteristics (chrome): when iron in the haeme is reduced and
allowed to bind to CO (or oxygen), the complex absorbs light in the visual spectrum
such that it becomes blue and violet colour at the wavelenght of maximum absorption
450nm
• This peak of maximum absorption is called the Soret Peak or Soret Band named after
its discoverer Jacques louis Soret

NOMENCLATURE

➢ Depending upon the extent of amino acid sequence homology, the cytochrome p450
isoenzymes are grouped in families designated by numericals (1,2,3…) each having
several subfamilies designated by capital letters (A,B,C…) while individual isoenzymes
are again alloted numericals (1,2,3…)
✓ Root:- CYP
✓ Family:- CYP 2
✓ Subfamily:- CYP 2 D
✓ Isoenzyme:- CYP 2 D 6
➢ All isoenzymes in the same family have at least 40% structural similarities and those
in the same subfamilies have 60% structural similarities
➢ In human beings only a few members of three isoenzyme families namely CYP 1, 2
and 3 carry out metabolism of most of the drugs
➢ Substrate: The agent which is metabolized by an enzyme into a metabolic end product.
➢ Inhibitor: An agent that interfere with or inhibits the functioning of enzyme that
metabolize a substrate. Enzyme inhibition are of two types - competitive and non-
competitive.
➢ Inducer: An agent that causes the target organ to produce more of an enzyme leading
to increase metabolism of the substrate of the induced enzyme.
PROPERTIES CYP 450 ENZYME

1. All are haemoprotiens

2. Liver contains the highest amount but found in other tissues including small intestine,
kidney, adrenals, lungs

3. Located in smooth endoplasmic reticulum or mitochondria

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4. They have a molecular mass of about 55KDa

5. Basically they catalyze oxidation reaction involving introduction of one atom of oxygen into
the substrate and one atom into water

6. Involved in the phase I of the metabolism of innumerable xenobiotics including 50% of drugs
administered

7. Involved in the metabolism of many endogenous compounds

8. Often exhibit broad substrate specificity thus acting on many compounds

9. They are inducible, resulting in one cause of drug interaction

10.Many are inhibited by various drugs or their metabolic products, providing another cause
of interaction

11.Some exhibit genetic polymorphism, which can result in atypical drug metabolism

12.Also their activity is altered by diseased state affecting drug metabolism

APPLICATION IN PSYCHIATRY

1. Drug interactions:

➢ The most common cause of altered drug biotransformation reaction are induction and
inhibition of CYP 450 enzyme
➢ Such drug interactions are especially important to take into account when using drugs
of vital importance to the patient, drugs with important side effects and drugs with small
therapeutic windows, but any drug may be subject to an altered plasma concentration
due to altered drug metabolism
➢ CYP 450 enzyme and antidepressants: The CYP 450 enzyme follows the principle of
transforming substrate into products
➢ The five most important enzyme for antidepressant and mood stabilizer drug
metabolism are:
1. CYP 450 1A2
2. CYP 450 2C9
3. CYP 450 2C19
4. CYP 450 2D6
5. CYP450 3A4
1.CYP 450 1A2:

➢ Substrates for this enzyme includes mainly the tricyclic antidepressants (TCAs)
specially the tertiary amines like clomipramine and imipramine
➢ Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which is a substrate as
well an inhibitor of the enzyme CYP 450 1A2, besides this other SSRIs like fluoxetine,
paroxetine, sertraline, and other antidepressants like bupropion and venlafaxine are
moderate to low inhibitors of this enzyme
➢ When these drugs are given concomitantly with other drugs that are metabolized by
this enzyme, those drugs can no longer be metabolized efficiently and would lead to

254
 their accumulation in blood e.g. when fluvoxamine is given with theophylline or warfarin
increase blood levels of these drugs may precipitate seizure or bleeding disorders

2.CYP 450 2D6:

➢ TCAs are substrate for 2D6 which hydroxylate them and thereby inactivates them
➢ SSRIs - paroxetine and fluoxetine have the most potent 2D6 inhibition and
fluvoxamine, sertraline the least potent
➢ One of the most important drug interaction that SSRIs can cause through inhibition of
2D6 is to raise the plasma level of atypical antipsychotics and TCAs if given
concomitantly

3.CYP 450 3A4 :

➢ Substrates for this enzyme includes benzodiazepines like alprazolam and triazolam,
and other nonpsychotropic drugs like cisapride, terfenidine and astemizole
➢ Some antidepressants like SSRIs fluoxetine, fluvoxamine and nefazodone are 3A4
inhibitors and concomitant use of these drugs can have adverse outcome

4. CYP 450 and mood stabilizers:

➢ Mood stabilizer and anticonvulsant carbamazepine which is both a substrate and an

inducer of 3A4
➢ With chronic treatment with carbamazepine 3A4 is induced and carbamazepine blood
levels will fall and failure to recognise this effect and to increase carbamazepine
dosage to compensate for it may lead to failure of anticonvulsant or mood stabilizing
efficacy of the drug
➢ Carbamezapine undergoes autoinduction
➢ Sodium valproate is an inhibitor of 2D6. It increases the levels of Lamotrigine.
5. CYP 450 enzyme and antipsychotics:

i). CYP 450 1A2:

➢ Three atypical antipsychotics are substrate for 1A2 namely olanzapine, clozapine and
zotepine
➢ When given with fluvoxamine (enzyme inhibitor) their levels will rise which may not be
clinically much significant for olanzapine except for some increase sedation but in case
of clozapine and zotepine the risk for seizures are increased
➢ People who are smokers, use of these drugs may need higher doses, as tobacco is
an inducer and if not checked a relapse of symptoms may occur
ii). CYP 450 2C9:

➢ The new dopamine partial agonist (DPA) bifeprunox is a substrate of 2C9 and its levels
are increased by co-administration of a 2C9 inhibitor like fluconazole, fluoxetine or
amiodarone
iii). CYP 450 2D6:

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 ➢ Atypical antipsychotics like Risperidone, clozapine, olanzapine, aripiprazole are all
substrate for this enzyme
➢ Paliperidone a metabolite of Risperidone is itself an atypical antipsychotic
➢ It bypasses the 2D6 enzyme and therefore not affected by alteration of activity of the
enzyme
➢ Several antidepressants are inhibitors and their concomitant administration must have
to be considered because of the possibility of developing extrapyramidal syndrome
(EPS)
iv)CYP450 and others:

➢ Cigarette smoking, Alcohol induces the enzyme 1A2

➢ While grapefruit juice and caffeine inhibit CYP system
➢ Their concomitant use with the psychotropics can cause alterations in drug levels.

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Endogenous opioids / Opiate receptors / Endorphins / Endorphins/ What are
Endogenous opiates and their relevance to psychiatry?

ENDOGENOUS OPIODS

➢ Five distinct neurobiological opioid peptide systems or families have been described
➢ Each of these systems has a distinct genetic basis, separate biosynthetic pathways
and distinct precursor molecules
➢ The 5 families form the opioids in the body and they are:
1) The Proopiomalanocortin (POMC) – Beta endorphin
2) The Proenkephalin - Enkephalin
3) The Prodynorphin - Dynorphine
4) The Proorphanin or Pro OFQ/N - Nociceptin
5) The Endomorphin systems
Enkephalins:
➢ Enkephalin is a pentapeptide ending with either leucine ("leu") or methionine ("met")
➢ Both are products of the proenkephalin gene
➢ Enkephalins play many roles in regulating pain:
1. [met]-enkephalin acts through μ and δ-opioid receptors
2. [leu]-enkephalin acts through δ-opioid receptors
Endorphins:
➢ Endorphin is a contraction of term endogenous and morphine coined by Dr Eric Simon
➢ It is involved in neural transmission and pain suppression
➢ They are released naturally when a person is physically hurt or severely stressed and
leads to absence of pain during acute pain

Dynorphins:
➢ Dynorphin acts through κ-opioid receptors
➢ Widely distributed in the CNS, including in the spinal cord and hypothalamus, arcuate
nucleus
➢ Also found in oxytocin and vasopressin neurons in the supraoptic nucleus
➢ Blocking dynorphin may help alleviate depression

Endomorphins:
➢ Endomorphins are produced by the pituitary gland and the hypothalamus
➢ Also secreted into the circulation from pituitary corticotropes and melanotropes
➢ Acts through μ-opioid receptors, and is more potent than other endogenous opioids at
these receptors

Nociceptin:
➢ Nociceptin is an opioid-related peptide, a potent anti-analgesic
➢ It is found in many regions of CNS e.g. hypothalamus, brainstem, forebrain, as well as
in the ventral and dorsal horns of the spinal cord
➢ Nociceptin acts at the NOP1 receptor, formerly known as ORL-1

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FUNCTIONS:

1. Analgesic by decreasing pain. The reason pain reduces is because it breaks down
bradykinins, which accumulate in response to injury
2. β-endorphin can also boost the immune system and kill cancer cells.
3. Promotes feeling of well-being, euphoria, self confidence
4. Increases relaxation
5. Increase sexual behaviour and appetite
6. Psychological Pain Relief

OPIOID RECEPTORS:

1. μ receptors:
➢ It has high affinity for morphine
➢ Sites:
1. Central nervous system (CNS)
2. The autonomic nervous system
3. To some degree opioid receptors on white blood cells
➢ The actions include:
1. Analgesia
2. Respiratory depression
3. Changes in mood (euphoria in some persons)
4. Indifference to anticipated distress
5. Drowsiness
6. Decreased ability to concentrate
7. Changes in endocrine and other functions regulated by the hypothalamus
8. Increased tone of smooth muscle in the gastrointestinal tract
➢ μ -Agonists also induce tolerance and neuroadaptive changes in the CNS that result
in distressing withdrawal phenomena when the agonist is stopped after days or weeks
of continuous use
➢ μ1: higher affinity for morphine, supraspinal analgesia.
➢ μ2: lower affinity for morphine, spinal analgesia
2. k receptors:

➢ Actions:
1. Dysphoria
2. Analgesia
3. No significant pupillary change
➢ k-agonists inhibit dopamine release
➢ k1: spinal analgesia
➢ k3: supra-spinal analgesia
3. δ receptors:

➢ Mediates spinal and the affective component of the supraspinal analgesia

➢ Also responsible for dependence and reinforcing actions and proconvulsant actions

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4. σ receptor:

➢ Little or no analgesia
➢ As the binding to the σ receptor is not antagonized by naloxone, it is no longer
considered an opioid receptor.
5. OFQ/N (ORL-1):

➢ It is identified by its high degree of homology to traditional opioid receptors

➢ Because it did not bind any of the ligands that were bound by the classic opioid
receptors, it was initially called an orphan receptor
➢ An endogenous ligand to this receptor was termed orphanin FQ by one researcher and
nociceptin by another
➢ The receptor has analgesic properties

Opioid Receptors:

➢ Opioid receptors are typical G-protein coupled receptors

➢ Receptors can be linked either to second messenger systems or directly to ion
channels
➢ m-Receptors, for example, can act via Gi or Go to directly increase potassium flux or
to inhibit the action of adenylate cyclase
➢ Subsequent decreases in the activity of cyclic adenosine monophosphate (cAMP)-
dependent protein kinases can have immediate effects on phosphorylation-dependent
cellular proteins as well as long-term effects on gene expression via decreased
phosphorylation of cAMP-dependent transcription factors, such as cAMP response
element binding protein (CREB)
➢ The endogenous opioids have significant interactions with other system commonly DA
and NE
➢ The addictive properties of opioids are mediated through activation of ventral
tegmental area dopaminergic neurons that project to cortex and limbic system

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Melatonin

INTRODUCTION:
➢ 5-methoxy-N-acetyltryptamine, it is a hormone found in all living creatures from
algae to humans, at levels that vary in diurnal cycles.

SYNTHESIS:
➢ Location:
Produced by Pinealocytes in the Pineal gland, retina, lens and GI tract
➢ Production of melatonin by the pineal gland is under the influence of the
suprachiasmatic nucleus of the hypothalamus (SCN) which receives
information from retina about the daily pattern of light and darkness
➢ It is naturally synthesized from the amino acid tryptophan (via synthesis of
serotonin) by the enzyme 5-hydroxyindole-O-methyltransferase
FUNCTIONS

1.IMMUNE SYSTEM:

➢ Melatonin is an immunoregulator that enhances T cell production

➢ Increased immune system activity may aggravate autoimmune disorders
2.DREAMING:

➢ Increase in the vividness or frequency of dreams

➢ High doses of melatonin (50mg) dramatically increased REM sleep time and dream
activity in both narcoleptics and normal people
3.CIRCADIAN RHYTHM:

➢ There is a role of melatonin and the pineal gland in regulating sleep-wake cycles
(circadian rhythms)
➢ Normally, the production of melatonin by the pineal gland is inhibited by light and
permitted by darkness. For this reason, melatonin has been called "the hormone of
darkness"
➢ The secretion of melatonin peaks in the middle of the night, and gradually falls during
the second half of the night
4.ANTIOXIDANT:

➢ Melatonin is a powerful antioxidant that can easily cross cell membranes and the
blood-brain barrier
➢ Melatonin, once oxidized, cannot be reduced to its former state because it forms
several stable end-products upon reacting with free radicals
➢ Therefore, it has been referred to as a terminal (or suicidal) antioxidant
➢ The antioxidant activity of melatonin may reduce damage caused by some types
of Parkinson's disease, may play a role in preventing cardiac arrhythmia and may
increase longevity

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RECEPTORS

1) MT1 – Inhibits suprachiastmatic nucleus

Promotes wakefulness.
2) MT2 - Phase shifting
Circadian rhythm
3) MT3 – Not implicated in sleep

THERAPEUTIC USES:

1.Sleep disorder:

• Circadian rhythm sleep disorders - jet lag,shift worker, delayed sleep phase syndrome
• Insomnia

2.Studied for the treatment of cancer, immune disorders, cardiovascular diseases, depression,
seasonal affective disorder (SAD), and sexual dysfunction

3.Melatonin may play a significant role in modulating the effects of drugs of abuse such as
cocaine

4.Learning, Memory and Alzheimers:

1. Melatonin can alter electrophysiological processes associated with memory, such as

long-term potentiation (LTP)
2. Melatonin prevent the hyperphosphorylation of the tau protein so formation of
neurofibrillary tangles, a pathological feature seen in Alzheimer's disease
3. Thus, melatonin may be effective for treating Alzheimer's Disease.
5.Preventative treatment for migraines and cluster headaches

APPLICATIONS: Agomelatin, Tasimelatin, Ramelteon

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Neuro Modulators

Neuromodulators can be distinguished from the classic neurotransmitters by several criteria:

1.The amount of expression is generally lower than that of neurotransmitters

2.In contrast to neurotransmitters, neuromodulators are effective at low concentrations

3.Normally, neuromodulators are incapable of inducing the rapid changes in signal transmission
which may be seen with neurotransmitters. They exert slow and long-lasting actions, mainly by
affecting G protein-coupled receptor and subsequent second messenger systems

4.Neuromodulators act indirectly by interacting with neurotransmitters (in such cases, they
coexist with neurotransmitters in the nerve terminals). Their direct effects on synaptic
transmission are weaker than those of neurotransmitters

5.Specific rapid inactivation mechanisms, as e.g. re-uptake mechanisms are rare

Neuromodulators are divided into:

1. Neuropeptides
2. Amino Acid derivatives
3. Gaseous Molecules
Neuropeptides with classic neurotransmitter effects are named co-transmitters

I - NEUROPEPTIDE
➢ Neuropeptides are a chain of two or more amino acids linked by a peptide bond and
differs from other proteins only in length of the amino acid chains
➢ Neuropeptides range in length from two - 40 amino acids

Types of neuropeptides:

1. Hypothalamic neuropeptides: CRH, thyrotropin-releasing hormone (TRH), growth

hormone-releasing hormone (GHRH), somatostatin (SOM), vasopressin, oxytocin (OT),
prolactin releasing factor (PRF), prolactin inhibiting factor (PIF).

2. Brain-born pituitary neuropeptides: Adrenocorticotropic hormone (ACTH), α- melanocyte

stimulating hormone (MSH), β-endorphine, thyroid stimulating hormone (TSH), luteinising
hormone (LH), prolactin, growth hormone (GH).

3. Brain-born opioid peptides: Enkephalins, endorphins, dynorphins, endomorphines,

nociceptin.

4. Brain-born gut peptides: Substance P (SUB-P), neuropeptide Y (NPY), vasointestinal

peptide (VIP), cholecystokinin (CCK), galanin, gastrin, motilin, pancreatic polypeptide,
neurotensin (NT)

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5. Others: Calcitonin gene related peptide (CGRP), cocaine amphetamine related transcript
protein (CARTP), atrial natriuretic peptide (ANP)/brain natriuretic peptide (BNP), orexin

Biosynthesis of neuropeptides:

1. Transcription of messenger ribonucleic acid (mRNA) from a specific gene

2. Translation of a polypeptide preprohormone encoded by the mRNA

3. Posttranslational processing of the prohormone to an active polypeptide

Each neuropeptide gene is expressed in brain and DNA sequences regulate expression of it

Neuropeptide receptors and signalling Receptors:

➢ Majority of neuropeptide receptors are G-protein coupled seven transmembrane
domain receptors
➢ Each neuropeptide receptor is specifically coupled to one type of G-protein e.g.
Gi/Gs/Gq and receptor activation may result into stimulation or inhibition of second
messenger pathways
➢ The receptors and their subtypes can be modulated by more than one type of
neuropeptides

Signalling:
Following binding of the peptide to its receptor a cascade of event takes place and the outcome
of which depends mostly on the type of cell and circuits in which the receptors are expressed

Clinical relevance of neuropeptides:

Neurotensin:
➢ NT gene is located on chromosome number 12q21 and its actions are mediated by 3
receptors, NT1, NT2 and NT3, out of which NT1 and NT2 are G-protein-coupled
receptors and NT-3 is a type 1 amino acid receptor
➢ NT is closely related to the transmission of neurotransmitters in the mesolimbic,
mesocortical and nucleus accumbens pathways which are the major sites of
dysregulation in schizophrenia
➢ NTs are predominantly located on gamma-aminobutyric acid (GABA)-ergic neurons
which releases GABA on dopaminergic nerve terminals and thereby inhibiting their
release
➢ Postmortem studies on brain tissues of schizophrenic patients showed decrease
expression of NT receptors and also a decrease in CSF concentration of NT compared
to their controls and after 4 weeks of treatment with antipsychotics the levels of NT
increased with improvement of symptoms
➢ Thus NT may act as an endogenous antipsychotic like substance and awaits the
development of NT receptor agonist that can penetrate the blood-brain barrier (BBB)

Cholecystokinin:
➢ CCK was originally discovered in the gastrointestinal tract and found in areas of brain
that are associated with emotion, motivation and sensory processing

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 ➢ It is colocalised with dopamine (DA) in the ventral tegmental area (VTA) neurons in the
mesolimbic and mesocortical DA circuits
➢ CCK inhibits DA
➢ Post-mortem brain quantitative analysis showed reduced expression of CCK mRNA
by 83% in the frontal lobe, 63% in the temporal lobe and in the layer 3 and layer 4 of
entorhinal cortex and CA1 region of hippocampus

Opioid peptides:
➢ Opioid neuropeptides frequently coexist with other neuropeptides or neurotransmitters
in the hypothalamic paraventricular nucleus (PVN), nucleus accumbens, substantia
niagra and spinal dorsal root neuron
➢ CSF studies of schizophrenic patients showed higher fraction-1 (opioid receptor active
fraction) level of endorphins and a higher level of this fraction was related to low level
of homovanillic acid (HVA), a metabolic product of dopamine
➢ Post-mortem brain studies showed high level of γ and ∝ endorphine levels in the
hypothalamus
➢ It was found that β-endorphine inhibits the release of dopamine mediated by N-methyl-
D-aspartic acid (NMDA) receptors in the nucleus accumbens and caudate nucleus and
putamen
➢ Again infusion of dynorphin into bilateral dorsal part of hippocampus showed
impairment of spatial learning and memory that is mediated through the opioid receptor
➢ This impairment was blocked by the administration of naloxone (an opioid receptor
antagonist)
➢ Thus it seems that opioid peptides may be responsible for the cognitive and learning
impairments in schizophrenia and which can be reversed by the use of opioid receptor
antagonist

Corticotropin-Releasing Factor:
➢ It is a 41 amino acid peptide located in chromosome number 8q13 with two receptors
CRF1 and CRF2
➢ CRF along with urocortin globally coordinate response to stressors
➢ Patients with early life trauma (child abuse or neglect) exhibit increase CSF CRF
concentration
➢ Also increased CSF CRF Concentration has now been demonstrated in patients with
major depression, posttraumatic stress disorder (PTSD) and antisocial personality
disorder
➢ Chronic hyperactivation of the stress system leads to increase and prolong production
of CRF which is regarded to play a pivotal role in the manifestation of chronic stress
syndrome
➢ If CRF hypersecretion is a factor in pathophysiology of depression, then reducing or
interfering CRF neurotransmission might be an effective strategy to alleviate
depressive symptoms
➢ Thus ‘CRF receptor antagonist’ that can penetrate BBB is a new class of agent for
treatment of anxiety and depression e.g. R-121919 and ∝-helical CRF 9-41

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Thyrotropin-Releasing Hormone:
➢ Gene for TRH is located in chromosome number 3q13.3-q21. TRH is known to
modulate several different neurotransmitters including DA, serotonin (5-HT),
acetylcholine (Ach) and opioids
➢ Chronic stress causing activation of the hypothalamic-pituitary-thyroid (HPT) axis is
associated with decrease production of thyroid-stimulating hormone (TSH) and
inhibition of conversion of relatively inactive thyroxin (T4) to more biologically active
triiodothyronin (T3) in peripheral tissues
➢ Radioimmunoassay studies of the HPT axis along with observations that primary
hypothyroidism is associated with depressive symptomatology ensured the
involvement of this axis in affective disorders
➢ It was found that a TRH stimulation test done in patients with major depression
revealed blunting of TSH response
➢ This blunting is a reflection of pituitary TRH receptor downregulation due to median
eminence hypersecretion of endogenous TRH
➢ CSF quantitative estimation for TRH concentration showed elevated levels in
depressed patients
➢ Thus, TRH hypersecretion may be associated with depression and an antagonist to it
may help in treating the condition

Vasopressin and oxytocin:

➢ The human OT and arginine vasopressin (AVP) genes are situated in head to tail
fashion on chromosome number 20p13
➢ The action of OT is mediated through single receptor subtype (OTR) distributed in
periphery and limbic system whereas the action of AVP is through three receptor
subtypes V1a, V1b (CNS) and V2 (kidney)
➢ AVP is colocalised with CRF neurons in the parvocellular neurons of PVN and acts
through the V1b receptors present in the adenohypophysis
➢ Post-mortem studies have shown an increase in the number of PVN AVP neurons
colocalised with CRF cells in depressed patients compared to controls
➢ Recently a nonpeptide V1b receptor antagonist SSR 149415 has been developed and
reported to possess both anxiolytic and antidepressant effects in animal models
➢ OT/AVP neurons projections from PVN to forebrain and brain stem regulate learning,
memory, complex social behaviour, female sexual behaviour and facilitate maternal
behaviour
➢ CSF studies of OT levels in persons with early exposure to stressful life situations
showed a reduced concentration of OT indicating that a dysregulation of this peptide
in psychiatric illnesses like autism

Neuropeptide Y:
➢ A 36-amino acid peptide found in hypothalamus, limbic structures, spinal cord and is
involved in the regulation of appetite, reward and anxiety
➢ Plasma levels of NPY is elevated in soldiers subjected to uncontrollable stress of
interrogation and NPY levels correlate with the feeling of dominance and confidence
➢ CSF and plasma levels are found to be reduced in depressive patients
➢ Post-mortem brain studies of suicide victim showed decrease expression of NPY in
the PFC

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II – AMINO ACIDS

1. GLUTAMATE

Acidic amino acid Neurotransmitter, with a carboxylic acid component to its side

SYNTHESIS:
• Glutamate is impermeable to the Blood-Brain Barrier
• Glutamate in the CNS is mostly formed by Glutamine as a precursor
• The concentration of Glutamine in the Glial cells is 50 times that in the synaptic cleft

• Glutamine Glutamate + NH4

Glutaminase
• Glutamine receptors are seen on neurons and glia and are called excitatory amino acid
receptors

As a neurotransmitter:

➢ Glutamate is the most abundant fast excitatory neurotransmitter of brain

➢ Concentration in brain – 10Mm
➢ At chemical synapses, glutamate is stored in vesicles
➢ Nerve impulses trigger release of glutamate from the pre-synaptic cell
➢ In the opposing post-synaptic cell, glutamate receptors, such as the NMDA receptor,
bind glutamate and are activated
➢ Has a role in synaptic plasticity, and may be involved in cognitive functions like learning
and memory
➢ Glutamate transporters are found in neuronal and glial membranes
➢ They rapidly remove glutamate from the extracellular space

RECEPTORS:
2 Broad Categories:
1. Ligand mediated (ion channel): Rapid Action
2. Metabotropic (G protein linked superfamily): Slower Action
➢ Ligand mediated on basis of Agonists are further divided into:
• NMDA or N methyl -D-Aspartate –NR1, NR2A, NR2B, NR2C, NR2D
• AMPA or alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate: GluR1-R4
• Kainate Receptors from Kainic acid derived from seaweeds – Glu R5-R7
➢ Metabotropic Glutamate Receptors:
• G-protein linked
• Play an important role in modulating pre-synaptically and post-synaptically the
effects of glutamate at glutamatergic synapses when the iGluRs are also
involved
• Located predominantly pre and peri-synaptically
• Group I may enhance NMDA receptor mediated neuronal degeneration, may
exacerbate seizures
• Group II and III are protective against neurotoxicity, attenuate seizures

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CLINICAL USES:
1. Schizophrenia
2. Depression
3. Anxiety,fear
4. OCD
5. Alcohol dependence
6. ADHD
7. Autism
8. Tourettes syndrome
9. Epilepsy

2. GABA:

➢ Gamma-aminobutyric acid (GABA) - chief inhibitory neurotransmitter in the CNS and

also in the retina

➢ SYNTHESIS:

Glutamate

Glutamate decarboxylase (GAD)

GABA

➢ RECEPTORS:

GABA receptor are of three general classes:

1. GABA A
2. GABA B
3. GABA C

Ionotropic Receptors:
➢ GABA A and GABA C which are ion channels themselves
➢ The binding of GABA to GABA-A receptors increases the Cl- conductance of
presynaptic neurons
Metabotropic Receptors:
➢ GABA B is a G protein-coupled receptors that open ion channels via intermediaries (G
proteins)
➢ Act by increasing conductance of an associated K+ channel

CLINICAL USE:
1. EPILEPSY- GABA maintain inhibitory tone; Blockade leads to seizure

2. SCHIZOPHRENIA-
➢ Decreased expression of m-rna
➢ Decreased GABA receptor density
➢ Changes in PFC leads to increased release of DA results in psychotic symptoms

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 3. DEPRESSION- CSF GABA levels are low

4. MANIA- GABA is increased

ASPARTATE:
➢ Aspartic acid is the carboxylic acid analog of asparagine
➢ It is non-essential in mammals, and might serve as an excitatory neurotransmitter
➢ Also, a metabolite in the urea cycle, and participates in gluconeogenesis
➢ As a neurotransmitter, aspartic acid may provide resistance to fatigue and thus lead to
endurance, although the evidence to support this idea is not strong

GLYCINE:
➢ Glycine is a non-essential amino acid NT
➢ An inhibitory neurotransmitter in the CNS, especially in the spinal cord, brainstem and
retina. When glycine receptors are activated, Cl- enters the neuron via ionotropic
receptors, causing an Inhibitory postsynaptic potential (IPSP)
➢ Strychnine is an antagonist at ionotropic glycine receptors
➢ Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast
to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the
(NMDA) glutaminergic receptors which are excitatory.

III – GASEOUS NTs

1. NITRIC OXIDE(NO):
➢ Atypical NT
➢ Also known as EDRF(endothelial derived relaxing factor)
➢ Produced post synapticaly
➢ No presynaptic storage
➢ Acts directly on intracellular protein
➢ Retrograde neurontransmitter
➢ No reuptake

SYNTHESIS:

Arginine

NOS – NO

Citrulline

TYPES:
1. n NOS
2. e NOS
3. i NOS

Target is active site of Guanyl cyclase(GC):

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 ➢ GC activation leads to formation of Cgmp
➢ The Action of cGMP is terminated by phosphodiesterase(PDE)

FUNCTION:
➢ Vasodilator
➢ Penile Erection
➢ Peristalsis
➢ Inflammation and immunity
➢ Vascular hemostasis
➢ Role in memory formation, sleep, neuronal plasticity and neurotoxicity

CLINICAL USES:

1. Mood disorder
2. Schizophrenia
3. Neurodegenrative disorder

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Neuropeptide Y

NEUROPEPTIDE Y:

INTRODUCTION:
➢ Neuropeptide Y (NPY) is a 36 amino acid peptide neurotransmitter found in the
brain and autonomic nervous system
➢ It augments the vasoconstrictor effects of noradrenergic neurons
➢ SITE: Hypothalamus, brainstem, spinal cord
➢ Co localised with NE,5HT

RECEPTORS: 5 subtypes

1. Y1,Y5 – Stimulation of appetite

2. Y2,Y3,Y4 - Satiety

FUNCTIONS:
1. Associated with a number of physiologic processes in the brain, including the
regulation of mood, anxiety, energy, memory, learning
2. Role in regulation of feeding:
➢ NPY's form part of the "lipostat" system along with leptin and corticotropin-
releasing hormone (CRH)
➢ High NPY levels in the CSF are associated with high food intake and
decreased physical activity

CLINICAL USE:
1.DEPRESSION:
➢ Facilitates emotions after stress
➢ suicide victims have low NPY
➢ MDD shows low levels of NPY
➢ Long term anti-depressant therapy improves NPY levels in frontal
cortex
2. ANXIETY DISORDER:
➢ NPY is anxiolytic
➢ High levels of NPY better performance during stress
3. PTSD:
➢ Low levels NPY
➢ High level NPY leads to resilience and protects against PTSD allowing
individuals to perform well under stress
• ALCOHOL USE:
➢ Low NPY leads to higher intake of alcohol

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Neurotrophic factors/ Neurotrophins/ What are Brain Derived Neurotrophic
factors (BDNF) and their role in the perpetuation of depressive illness?

DEFINITION:

Neurotrophic factors are family of polypeptide growth factors having a vital role in proliferation,
differentiation, survival and death of neuronal and non-neuronal cells

Components of Neurotropin family:

1. Nerve growth factor

2. Brain derived neurotrophic factor

3. Neurotrophin-3

4. Neurotrophin 4/5

5. Glial derived neurotrophic factor

6. Ciliary neurotrophic factor

SYNTHESIS:

proneurotrophins

furin or proconvertones

active proteins / mature protein (NF)

Expressed during neuronal development for selective neuronal survival

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 BRAIN DERIVED NEUROTROPHIC FACTOR(BDNF)

Pre-pro BDNF

acts via- p75 pro BDNF

mature BDNF - acts via trkB

LOCATION:

NGF:

Cns-basal forebrain projections to hippocampus

Pns-sensory & sympathetic neurons

BDNF,NT-3 -: cortical, hippocampus

RECEPTORS:

1. Trk –TYROSINE KINASE Receptor: Survival

2. P-75 NEUROTROPHIN RECEPTOR [NTR]: Apoptosis
➢ GENES FOR Trk receptors: Trk A, Trk B, Trk C
RECEPTOR SPECIFICITES:

NGF NT3 BDNF NT3 NT4 NT3

Trk A Trk B Trk C

Neurotrophin hypothesis:

➢ Neurons compete for neurotrophic factors for their survival and this depends on on
level of factors and receptors
➢ High affinity binding sites allows for greater response
➢ Incorrect targeting of axon results in apoptosis
➢ After which factors are released from target tissue and transported back to presynaptic
neuron to convey message about target tissue condition
➢ This is carried out by ‘RETROGRADE TRANSPORT’ signalling endosomes

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FUNCTIONS BDNF:

1. Trophic role

2. Apoptotic role

3. Synaptic plasticity

4. Neurotransmitter release & potentiation

5. Regulation of gene expression

6. Pain regulation

7. Learning, memory & behaviour

RELEVANCE TO PSYCHIATRY:

1. MDD
• Decreased BDNF: Dysregulation of synaptic plasticity and neuronal survival
leads to MDD
• Increased BDNF: Mesolimbic circuit leads to MDD
• BDNF polymorphism linked to MDD
Codon 66 –valine to methionine(v66m)
|
prevents release of BDNF

MRI FINDING
/ \
Reduction in hypertrophy of amygdala
hippocampal volume &nucleus accumbens
prefrontal cortex
limbic system |
|
Decreased BDNF Increased BDNF

Positive correlation with antidepressants:

➢ Increased BDNF in Hippocampus &cortex
➢ Upregulates BDNF transcription through CAMP pathway
➢ Serum BDNF normalized after treatment
➢ Trk B activation is required for antidepressants action
➢ Trk B downstream signalling is also required

2. BPAD:
➢ BDNF decreased in BPAD
➢ Lithium & valproic increases BDNF in corticolimbic pathway
➢ V66m BDNF allele is strongly correlated in BPAD

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 3. ANXIETY:
➢ BDNF increases the susceptibility to stress and anxiety

4. PTSD:
V66M MUTATION – impairs fear memory

DELETION OF BDNF

/ \

In amygdala in hippocampus
| |
Loss of fear memory extinction of fear
Acquisition memory

5. Schizophrenia:
MIXED RESULTS –studies show both increased &decreased expression of BDNF in cortex &
hippocampus due to:

➢ Altered developmental strategy

➢ Manifestation of disease pathology itself

➢ Antipsychotic action:

1. Increases BDNF: olanzapine, clozapine

2. Decreases BDNF – haloperidol, risperidone

6. ADDICTION:

COCAINE:

Incresed BDNF expression

|
long term potentiation
|
synaptic plasticity
|
Increased drug seeking behaviour
INCREASED BDNF EXPRESSION IN:
BDNF –Trk B
/ \
D1 receptor neurons D2 receptor neurons
Dampens rewarding enhances rewarding
MORPHINE: Decreased serum BDNF
NICOTINE: BDNF-TrkB polymorphism enhances reward seeking in smoking
ALCOHOL: Decreased BDNF in serum

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7. EATING DISORDER:

➢ Loss of BDNF – increase weight gain, hyperphagia

➢ Infusion of BDNF –shown to reduce the weight

8. SUICIDE:

Early stress

methylation of BDNF DNA

reduces BDNF expression

suicidal risk

9. Neurodevelopmental disorder:

➢ Rett syndrome:
➢ Mecp2 gene mutation >decreased BDNF expression > abnormalities in development
of brain
10. Neurodegenerative disorders:

1. Peripheral neuropathies
2. Amyotrophic lateral sclerosis
3. Alzheimers disease
4. Parkinsonism
5. Hutingtons chorea

11. OTHERS:

NGF:
1. Vital for development of PNS
2. Thereupetic role in diabetic neuropathy
3. Cholinergic neuron development
GDNF: In nigrostriatal dopaminergic pathway
BFG, IGF, TGF:
➢ Role in hypoxic injury
➢ Ischemia
CNTF:
➢ Development of motor neurons
➢ Therapeutic agent in motor neuron disease

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Novel Neurotransmitters

INTRODUCTION:

➢ Within the past few decades the discovery of novel neurotransmitters has led to a
reformulation of these strict criteria
➢ Messengers such as the gases, cannabinoids, and eicosanoids are not stored in
vesicles in presynaptic neurons, but appear to be generated and released “on demand”
➢ The endocannabinoids appear to have an important role in transmitting signals
backward, that is, from the postsynaptic neuron to the presynaptic neuron
➢ Finally, the gases do not act upon a receptor on the extracellular membrane of a
postsynaptic neuron, but diffuse into the cell and act directly upon multiple cellular
proteins, bypassing membrane receptors entirely
➢ Nitric oxide may then serve as a candidate retrograde messenger, diffusing back to
the presynaptic neuron to facilitate further neurotransmission
➢ Other candidate retrograde messengers include arachidonic acid, cannabinoids,
platelet activating factor, and carbon monoxide

Novel Neurotransmitters:

Neurotransmitters are chemicals that amplify or inhibit the depolarization signal from one
neuron to that of an adjacent neuron

1.Gases as neurotransmitters

a. NO
b. CO
c. H2S
2. Endocannabinoids
3. Eicosanoids
4. Neurosteroids

NITRIC OXIDE(NO)

Atypical NT

➢ Also known as EDRF(endothelial derived relaxing factor)

➢ Produced post synapticaly.
➢ No presynaptic storage.
➢ Acts directly on intracellular protein.
➢ Retrograde neurontransmitter
➢ No reuptake

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SYNTHESIS:
Arginine
| NOS – NO
Citrulline

TYPES: n NOS, e NOS, i NOS

1. Target is active site of guanyl cyclase(GC)

2. Once GC is activated and cGMP is formed
3. The Action of cGMP is terminated by phosphodiesterase(PDE)

FUNCTIONS:

1. Vasodilator
2. Penile Erection
3. Peristalsis
4. Inflammation and immunity
5. Vascular hemostasis
6. Role in memory formation, sleep, neuronal plasticity and neurotoxicity

CLINICAL USE:

1. Mood disorder
2. Schizophrenia
3. Neurodegenrative disorder

ENDOCANNABINOIDS:
SYNTHESIS
➢ Synthesized from ARACHIDONIC ACID.
➢ It is not stored. It is synthesized as per requirement and released on neuronal
depolarisation with influx of Ca2+.
ENDOGENOUS CANNABINOID [EC]
6. Anandamide
7. N-Arachidonoyl Dopamine (NADA)
8. 2-arachidonoylglycerol (2-AG)
9. 2-arachidonoylglycerol ether (2-AGE)
10. Virodhamine
INACTIVATION
1.Reuptake
2.Enzymatic degradation
➢ Endocannabinoids are metabolized by intracellular enzymes.
➢ Anandamide is metabolized by fatty acid amide hydrolase (FAAH). FAAH is expressed
in the soma and dendrites of neurons.
➢ 2-ArachidonoylGlycerol is metabolized by monoacylglycerol lipase (MGL). MGL is
distributed in presynaptic terminals.

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RECEPTORS
CB1 & CB2 are G protein coupled receptors.
CB1 – cortex,cerebellum,basal ganglia.
CB2 – WBC,immune system.

➢ Gs-stimulates adenyl cyclase.Gi/o – inhibits adenyl cyclase & other physpholipases.

➢ Endocannabinoid mediates short-Term Plasticity.
➢ They function as retrograde messengers at synapses in the CNS.

CLINICAL USE

1) SCHIZOPHRENIA:
➢ Large doses of THC can cause psychotic symptoms in normal individuals.
➢ THC may worsen psychotic symptoms in Schizophrenic patients.
➢ THC decreases effectiveness of antipsychotic drugs.
➢ Use of cannabis may precipitate schizophrenia in susceptible individuals.
➢ Treatment with anti-psychotics appears to normalize imbalance in EC signaling in
blood cells of Schizophrenic patients.
➢ Cannabidiol has been shown to have anti-psychotic potent. E.C.S. may be a novel
therapeutic target in Schizophrenia.

2) MDD AND ANXIETY:

➢ Lower doses – calmness, anxiolytic effect & euphoria
➢ Higher doses – dysphoria & anxiety
➢ Lower doses of THC & CP 55940 – anxiolytic
➢ Pharmacological CB1 signaling by FAAH inhibitors may have therapeutic value in
anxiety disorders, OCD and depression

3) ADDICTION:
➢ Genetic vulnerability to addiction is linked to functional deficiency in the second order
neuron
➢ CB1 increases extra cellular dopamine in nucleus accumbens
➢ CB1 also increases firing rates of dopaminergic neurons

4)NEUROPROTECTIVE:
➢ Endocannabinoids decreases brain edema, infarct size, cell death and improves
cognition.
5)ANALGESIA:
➢ CB1 receptor mediates analgesia through vanallid receptor.

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NEUROSTEROIDS:

INTRODUCTION:

➢ Neurosteroids are synthesized from cholesterol in the brain

➢ Neurosteroids are produced by a sequence of enzymatic processes governed by
P450 and non-P450 enzymes either within or outside the mitochondria of several
types of CNS and peripheral nervous system (PNS) cells
➢ Receptors are generally located in the nucleus, membrane, or microtubules of the
CNS and PNS
➢ The most well-known effect of neurosteroids is on the GABA receptor, particularly
the GABAA receptor
➢ Some neurosteroids may also act at the NMDA, α-amino-3-hydroxy-5-methyl-4-
isoxazole-propanoic acid (AMPA), kainate, glycine, serotonin, sigma type-1, and
nicotinic acetylcholine receptors.
➢ Neurosteroids acting primarily at this site include allopregnanolone, pregnenolone
(PREG), and
tetrahydrodeoxycorticosterone,Progesterone,Dehydroepiandrosterone sulfate
(DHEA-S), the most prevalent neurosteroids.
FUNCTION

1.Neurodevelopment and Neuroprotection : Neurosteroids stimulate axonal growth and

promote synaptic transmission. Specific neuroprotective effects are unique to each
neurosteroid

2.DHEA acts to regulate brain serotonin and dopamine levels, suppress cortisol, increase
hippocampal primed burst potentiation and cholinergic function, decrease amyloid-β protein,
inhibit the production of proinflammatory cytokines, and prevent free radical scavenging

3.Progesterone helps in myelination

4.Allopregnenolone decreases contacts during axonal regression

CLINICAL USE

1. Depression: There is an inverse relationship between allopregnanolone concentrations

and severity of depressive illness.
2. Anxiety Disorders: Homeostasis characterized by normal GABAergic activity is
restored after panic attacks as neurosteroids are released in response to stress. Both
positive and negative regulation of the GABAA receptor is correlated with anxiolytic and
anxiogenic action, respectively.
3. Psychotic Disorders:
➢ DHEA has been dispensed to decrease anxiety in schizophrenics. DHEA and
DHEA-S levels are typically elevated in a schizophrenic's initial episode,
indicating neurosteroids are upregulated by the onset of psychosis
4. ADHD is inversely correlated with DHEA and pregnenolone levels
5. Substance Abuse:
➢ Levels of Pregnenolone, allopregnanolone, allotetrahydrodeoxycorticosterone
are increased in the brain and periphery in response to increases in peripheral
alcohol levels. It is hypothesized that sharp increases in ethanol concentration

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 may mimic the acute stress response and elevate neurosteroid concentrations
by the hypothalamic–pituitary–adrenal axis
6. Eating Disorders:
➢ DHEA has been shown to diminish food intake, temper obesity, moderate
insulin resistance, and lower lipids
7. Postpartum and Gynaecological Disorders:
➢ Low postpartum DHEA concentrations have been linked to mood instability. In
addition, allopregnanolone levels correlated with mood disorders during
pregnancy and in premenstrual syndrome (PMS)
➢ It has been noted that women with premenstrual dysphoric disorder have
higher allopregnanolone/progesterone ratios than normal controls
8. Neurosteroids, Memory Disorders, and Aging:
➢ Neurosteroid levels may be irregular in neurodegenerative disorders and aging
conditions such as Alzheimer's and Parkinson's. DHEA supplementation can
prevent or slow the cognitive declines associated with the aging process
➢ In Alzheimer's disease, the DHEA concentrations have been found to be
markedly decreased
EICOSANOIDS:

➢ These are unsaturated omega-3 fatty acids:

1. Eicosapentaenoic acid (EPA)
2. Docosahexaenoic acid (DHA)
➢ Omega-3 fatty acids are synthesized by algae and plankton
➢ Fish such as herring, salmon, mackerel, and anchovy feed on these aquatic species
and become a rich dietary source of omega-3
➢ EPA and DHA are highly unsaturated omega-3 fatty acids that contain 6 and 5 double
bonds on their long structural chain, respectively
➢ They are positioned in the cell membrane by phospholipids and play a crucial role in
cell membrane signaling
Therapeutic Indications:

1.Effects on Specific Organs and Systems:

➢ Omega-3 fatty acids lower blood pressure, reduce the rate of recurrent myocardial
infarction, and lower triglyceride levels
➢ In the nervous system, fatty acids are essential components of neurons, immune cells,
and glial phospholipid membrane structures
➢ They increase cerebral blood flow, decrease platelet aggregation, and delay
progression of atherosclerosis in the cardiovascular system
➢ Omega-6 fatty acids appear to reduce inflammation and neuronal apoptosis and
decrease phosphatidylinositol second messenger activity
➢ Omega-3 fatty acids have been suggested to alter gene expression
2. Mood disorders:

➢ Countries with lower per capita fish consumption had up to 60 times increased rates
of major depression, bipolar disorder, and postpartum depression
➢ Observational studies concluded that the lower incidence of seasonal affective
disorder in Iceland and Japan, rather than latitude predicted, is related to the amount
of fatty acid these populations consume in their diet

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 ➢ A study in Norway showed that use of cod liver oil decreased depressive symptoms
➢ Depression after a myocardial infarction shows higher arachidonic acid to EPA ratio
➢ Postmortem studies in brains of patients diagnosed with major depressive disorder
show reduced DHA in the orbitofrontal cortex
3.Developmental disorders:

➢ The most convincing evidence comes from early brain development and learning
studies
➢ Pregnant mothers who consumed foods rich in DHA gave birth to infants who had
improved problem-solving skills, but not necessarily improved memory
➢ Visual acuity and eye development are also associated with DHA supplementation
during pregnancy
4.Violence: Violent criminals identified lower levels of omega-3 fatty acids in their system

5. Psychosis:

➢ The negative and psychotic symptoms of schizophrenia may be improved with

supplementation with omega-3 fatty acids
➢ Antipsychotic medications like haloperidol (Haldol) appear to have fewer
extrapyramidal side effects when combined with antioxidants and omega-3 fatty acids
6. Dementia:

➢ EPA and DHA have been associated with decreased dementia incidence. high fish
consumption was inversely related to cognitive decline
➢ Omega-3 fatty acids can be recommended for prevention of cognitive impairment

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Prolactin

Introduction:

➢ Prolactin is a polypeptide hormone secreted by the lactotroph cells of the anterior pituitary
gland.
➢ Prolactin release is pulsatory with approximately 13–14 pulses a day and displays a
significant diurnal rhythm.
Regulation of prolactin secretion:

➢ Prolactin secretion is influenced by both stimulatory and inhibitory endogenous

substances. Its release is also indirectly influenced by the effects of exogenous
substances on the endogenous ones
➢ Prolactin secretion is regulated via tonic secretion of dopamine in the
tuberoinfundibular tract and the hypothalamo-hypophyseal vessels
➢ Dopamine acts as a prolactin-inhibiting factor on D2 receptors located on the
surface of the pituitary lactotroph cells, whereas serotonin stimulates prolactin
secretion
➢ The serotonin mediated increase is probably via stimulation of prolactin-releasing
factors
➢ Estrogen, opioids, substance P, and many other endogenous substances increase
prolactin secretion while major neurotransmitters such as gamma aminobutyric
acid (GABA) and acetylcholine inhibit prolactin secretion
➢ Levels increase shortly after sleep onset, peak during the night, and start to decline
shortly after waking, reaching a nadir around noon
➢ Food, especially a midday meal, increases prolactin levels
➢ Levels among individuals also tend to fluctuate over time and this is particularly
evident in post-menopausal women
➢ The primary physiologic role of prolactin is the induction of lactation
➢ Prolactin is also released in response to strong stimulatory effects on the nipple,
such as breastfeeding, and in response to stress
Diagnostic use

1. Prolactin levels may be checked as part of a sex hormone workup, as elevated

prolactin secretion can suppress the secretion of FSH and GnRH, leading to
hypogonadism and sometimes causing erectile dysfunction.
2.
Prolactin levels may be of some use in distinguishing epileptic seizures from
psychogenic non-epileptic seizures. The serum prolactin level usually rises following
an epileptic seizure.
Reference ranges

➢ Normal prolactin is 25 µg/L for women and 20 µg/L for men.

➢ Prolactin deficiency (hypoprolactinemia) are defined as prolactin levels below 3 µg/L
in women and 5 µg/L in men

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 ➢ However the prolactin levels also vary factors including age,] sex, menstrual cycle
stage and pregnancy
Hyperprolactinemia: Relevant to psychiatry

The causes of hyperprolactinemia are wide-ranging, with CNS disorders, various systemic
conditions, pituitary disorders, and antidepressant and antipsychotic medications all
implicated

As such, even in patients who receive prolactin inducing medications, other possible causes
of hyperprolactinemia should be considered

1. Systemic conditions

➢ The most prevalent systemic condition associated with hyperprolactinemia is stress in

response to psychologic, environmental, or internal stimuli
➢ Physical stress, whether brought about from normal exercise, medical conditions such
as hypoglycaemia or induced by surgery, may also cause hyperprolactinemia
➢ In addition, any impairment in prolactin metabolism, including advanced liver
dysfunction, cirrhosis, or chronic renal failure, may result in elevated prolactin levels
2. CNS and pituitary disorders

➢ Meningiomas, craniopharingiomas, sarcoidosis, disseminated autoimmune disorders,

and vascular impairments are all potential causes
➢ Tumors in the anterior pituitary, particularly prolactinomas, are one of the most
common causes of hyperprolactinemia
➢ Other pituitary disorders, such as empty sella syndrome and acromegaly, may also
elevate prolactin
➢ Magnetic resonance imaging and computed tomography scans that focus on the sella
turica are therefore essential in diagnosing hyperprolactinemia
3. Schizophrenia and antipsychotic-induced hyperprolactinemia

➢ Prolactin levels in a given untreated schizophrenic individual are the result of the
balance between multiple internal regulatory processes and external stimuli (e.g.
stressful events)
➢ The dopaminergic hypothesis for the pathobiology of schizophrenia was developed
mainly because the efficacious conventional (typical) antipsychotics were all
dopamine-blocking agents
➢ Their clinical efficacy was attributed to blockade of the mesolimbic and mesocortical
dopaminergic pathways, while the extrapyramidal adverse effects associated with
conventional antipsychotics were due to blockade of the nigrostriatal dopamine
pathway
➢ The tubero-infundibular system regulates prolactin secretion via dopamine neurones
➢ Dopamine from the tubero-infundibular system is secreted from the median eminence
of the hypothalamus, via the portal veins of the pituitary stalk, to the lactotrophs in the
anterior pituitary where it exerts its tonic-inhibitory effect. (There is a short feedback
mechanism between prolactin and dopamine released from the hypothalamus.)
➢ Therefore, any blockade of dopamine receptors in the tubero-infundibular system
would reverse prolactin inhibitory effects and lead to hyperprolactinemia

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 ➢ Typical antipsychotic agents are nonselective, blocking all dopamine pathways
including the tubero-infundibular pathway
➢ Indeed, it has been suggested that the magnitude of hyperprolactinemia may be a
biological marker for the therapeutic effects of an antipsychotic, and a very high
correlation between hyperprolactinemic effect and ‘therapeutic potency’ has been
demonstrated across a group of conventional antipsychotic drugs
➢ While antipsychotic-induced hyperprolactinemia is almost universal with typical
agents, most atypical antipsychotics do not cause a sustained elevation in prolactin
levels
➢ Conversely, risperidone induces hyperprolactinemia at least to a similar level to that of
the conventional neuroleptics
➢ In addition, there is some evidence that zotepine and amisulpride also induce
hyperprolactinemia
➢ Dopaminergic agonist Bromocriptine can be used to treat cases of
hyperprolactinaemia
3.4. Antidepressants and other medications:

➢ Some tricyclic antidepressants cause hyperprolactinemia, as do selective serotonin

reuptake inhibitors, due to their increased serotonergic stimulatory effects
➢ Similarly, d-fenfluramine, an ingredient in some weight-reduction products, increases
serotonin activity and can produce elevated prolactin levels
➢ Monoamine oxidase inhibitors, which increase activity of dopamine but also
norepinephrine and serotonin, have also been shown to induce hyperprolactinemia
➢ It has been reported that depletion of dopamine with reserpine has been shown to
increase levels of prolactin
➢ Several opioids, including morphine, cocaine, and β-endorphin, have been reported to
increase prolactin secretion through dopamine interaction
➢ The opioid antagonist naloxone and its long-acting counterpart naltrexone block
increase in prolactin, which might be caused by other stimuli such as stress and
surgery
➢ However, it is not yet clear whether these opioids actually decrease prolactin levels if
they are not already elevated
Clinical effects of hyperprolactinemia:

1. Decreased bone mineral density (BMD) and osteoporosis:

➢ The consequences of hyperprolactinemia-induced decreases in estrogen and

testosterone levels may lead to debilitating and long-term disease
➢ One of the most serious is osteoporosis
4.2. Prolactin and the immune system:

➢ Prolactin influences several interleukins and in turn is influenced by changes in

interleukin-2 and other interleukins
➢ Prolactin receptors have been identified on several blood cells, notably B-cells, T-cells,
and monocytes
➢ It has been suggested that prolactin is secreted from mononuclear cells and has an
autocrine/paracrine effect on immune-cell function

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4.3. Prolactin and the cardiovascular (CV) system:

➢ It is well documented that women of reproductive age suffer less from CV disorders
and cardiac infarction than men
➢ However, following menopause this gender difference disappears
➢ It has been suggested that the decreased prevalence of CV disorders in pre-
menopausal women is attributable to the protective effects of estrogen against
arteriosclerosis, hypertension, and raised cholesterol and triglyceride levels
➢ As such, the low estrogen levels that commonly occur with hyperprolactinemia may
increase the rate of CV disorders in this group
4.4. Prolactin and breast cancer:

➢ Increased levels of prolactin have been identified as a risk factor for breast cancer,
which is the most common malignant disorder among women and is a major cause of
death
4.5. Galactorrhea:

➢ Galactorrhea has been reported in 30–80% of women with hyperprolactinemia

associated with pituitary tumors but the reported prevalence of galactorrhea in patients
with schizophrenia taking antipsychotics is much lower
4.6. Influence of hyperprolactinemia on the menstrual cycle and fertility:

➢ As hyperprolactinemia is associated with suppressed estrogen levels, initial evidence

of elevated prolactin is often identified by reproductive-related symptoms, particularly
in women
➢ Symptoms include menstrual irregularities, anovulation and its sequelae, and
amenorrhea. These symptoms are often accompanied by galactorrhoea, breast
enlargement, or a feeling of engorgement
➢ However, the percentage of women on antipsychotics who report amenorrhea (33%)
is approximately twice the proportion who report galactorrhoea
4.7. Sexual dysfunction:

➢ Increased dopamine and decreased prolactin are associated with increased libido.
Increased nitric oxide and increased cAMP, as well as increased acetylcholine, are
needed for arousal and orgasm is associated with a decrease in serotonin and an
increase in norepinephrine levels
4.8. Mood and behavioural effects of hyperprolactinemia:

➢ Hostility, depression, and anxiety were reported to be more frequent in amenorrhoeic

women with hyperprolactinemia than in both amenorrhoeic women with normal levels
of prolactin and in women with regular menstrual cycles
➢ Similar mood symptoms have also been reported in response to elevated prolactin in
healthy women
➢ However, in men, the direct impact of increased prolactin on mood and behaviour is
still unclear

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286
Describe Polymerase chain reaction and its use in Psychiatry

INTRODUCTION:

•Polymerase chain reaction (PCR) is a technique used in molecular biology to amplify

a single copy or a few copies of a segment of DNA generating thousands to millions of
copies of a particular DNA sequence
• It is an easy, cheap, and reliable way to repeatedly replicate a focused segment of
DNA
• In 1993, Mullis was awarded the Nobel Prize in Chemistry along with Michael Smith
for his work on PCR
PROCEDURE:

1. Initialization:

➢ This step is only required for DNA polymerases that require heat activation by
hot-start PCR
➢ It consists of heating the reaction chamber to a temperature of 94–96 °C (201–
205 °F), or 98 °C (208 °F) if extremely thermostable polymerases are used,
which is then held for 1–10 minutes
2. Denaturation:

➢ This step is the first regular cycling event and consists of heating the reaction
chamber to 94–98 °C (201–208 °F) for 20–30 seconds
➢ This causes DNA melting, or denaturation, of the double-stranded DNA
template by breaking the hydrogen bonds between complementary bases,
yielding two single-stranded DNA molecules
3. Annealing:

➢ In the next step, the reaction temperature is lowered to 50–65 °C (122–149 °F)
for 20–40 seconds, allowing annealing of the primers to each of the single-
stranded DNA templates
➢ A typical annealing temperature is about 3–5 °C below the Tm of the primers
used
➢ Stable hydrogen bonds between complementary bases are formed only when
the primer sequence very closely matches the template sequence
➢ During this step, the polymerase binds to the primer-template hybrid and begins
DNA formation
4. Extension/elongation:

➢ The temperature at this step depends on the DNA polymerase used; the
optimum activity temperature for Taq polymerase is approximately 75–80 °C
(167–176 °F)
➢ In this step, the DNA polymerase synthesizes a new DNA strand
complementary to the DNA template strand

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 ➢ The precise time required for elongation depends both on the DNA polymerase
used and on the length of the DNA target region to amplify
➢ The processes of denaturation, annealing and elongation constitute a single
cycle
➢ Multiple cycles are required to amplify the DNA target to millions of copies
➢ The formula used to calculate the number of DNA copies formed after a given
number of cycles is 2n, where n is the number of cycles
➢ Thus, a reaction set for 30 cycles results in 230, or 1073741824, copies of the
original double-stranded DNA target region
• Final elongation:

➢ This single step is optional, but is performed at a temperature of 70–74 °C

(158–165 °F) for 5–15 minutes after the last PCR cycle to ensure that any
remaining single-stranded DNA is fully elongated
• Final hold: The final step cools the reaction chamber to 4–15 °C (39–59 °F) for an
indefinite time, and may be employed for short-term storage of the PCR products

APPLICATIONS:

Polymerase chain reaction (PCR) is a broadly applied laboratory test for the diagnosis of a
wide variety of central nervous system (CNS) diseases, including genetic and autoimmune
diseases, malignant neoplasms, and infection

With its ability to detect minute amounts of DNA or RNA contained in tissues or fluids, PCR
has improved the rapidity and accuracy of diagnosis, enhanced understanding of
pathogenesis, and helped identify infectious causes for diseases previously considered
idiopathic

1.Expression of TNF alpha from brain tissue of patient with CJD was found by reverse
transcription coupled PCR

2.RT PCR on brain tissues of patient - AIDS with dementia demonstrated elevated MIP 1 alpha
and MIP 1 beta m RNA expression.

3.APO E genotype in Alzeihmers dementia was determined by digestion of Apo E PCR

products with restriction enzyme CfoI.

4.In patients with alcohol consumption there is expression of gene coding for GSTM1 and
GSTT1 determined in granulocyte DNA by multiplex PCR technique.

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Basic Sciences
Miscellaneous
Question

289
 Animal models of dementia

INTRODUCTION:

➢ Dementia is the term used for memory loss. It can be limited to the inability to recall
recent events, events from the distant past, or a combination of both
➢ Memory loss may be permanent or temporary and depending upon the cause, it may
have either a sudden or gradual onset. i
➢ Although Alzheimer’s disease is the commonest form of dementia, there are many
other different types of dementia such as Creutzfeldt-Jakob disease, dementia with
Lewy Bodies, frontotemporal dementia, Huntington’s disease, Parkinson’s disease
vascular dementia and Wernicke-Korsakoff syndrome etc.ii
➢ Since newer drugs are being developed for the treatment of dementia, animal models
are essential to test the safety and efficacy of these drugs before testing them on
humans.
➢ This can be done by the following means:
1. Anti-Neurotransmitter Agents Induced Memory Loss
2. Toxin Induced Memory Loss- stereotaxic injection of various neuro-toxic
chemicals in certain regions of the brainiii
3. Transgenic models-mutant gene/s can be introduced into the rodents that
produces signs and symptoms of dementia in the progeny. iv
4. Mechanical brain injury-exposing the animals to a predetermined head injury. v
5. Using amnesic agents to induce reversible amnesia.vi

1) Anti-Neurotransmitter Agents Induced Memory Loss:

➢ A number of neurotransmitters and their respective receptors play a role in learning
and memory such as:
1. Acetylcholine
2. GABA
3. nor-epinephrine
4. dopamine
5. histamine
6. glutamate

The following are the animal models based on neurotransmitters:

A) Learning and memory in zebrafish were impaired by scopolamine using a passive

avoidance response test. Scopolamine impaired both the acquisition of passive
avoidance response and retention of the learned response.vii
B) Rats administered with tiagabine, a GABA transporters inhibitor, showed impaired
learning. GABA-A receptor agonists such as muscimol and GABA-B receptor
agonists such as baclofen are reported to impair memory in animals.viii ix x

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Toxin Induced Memory Loss:

Toxins which can be used are- Amyloid beta peptide, Kianic acid, Domoic acid and
Ibotenic acid.

A) Amyloid beta peptide:

➢ In vitro studies show that it decreases cell viability causing neuronal death
➢ Necrosis and apoptosis results from exposure to this peptide
➢ It can decrease choline uptake, inhibit acetylcholine (Ach) synthesis enzyme choline
acetyltransferase (ChAT) activity, and reduce Ach biosynthesis and release in
cholinergic neurons in brain
➢ This is the principal cause of cognitive dysfunction in patients with AD. xi xii xiii
B) Kainic acid:

➢ It is an agonist for a subtype of ionotropic glutamate receptor, which mimics the effect
of glutamate
➢ It has been shown to increase production of reactive oxygen species, mitochondrial
dysfunction, and apoptosis in neurons particularly in the hippocampal CA1 and CA3
regions, and in the hilus of dentate gyrus.xiv
➢ Intrahippocampal administration of kainic acid using stereotaxic coordinates in rats
induce cognitive dysfunction
C) Domoic acid:

➢ This naturally occurring marine biotoxin is the cause of amnesic shellfish poisoning
and an acute dose can cause vomiting, cramping, coma and death
➢ Microinjection of domoic acid into the hippocampus of rats produces degeneration of
CA3 and CA1 pyramidal cells and dentate gyrus granule cells leading to a long-
lasting memory.xv
➢ Domoic acid induced toxicity in the neuronal cells occurred due to imbalance in
intracellular Ca2+ homeostasis
➢ The Ca2+ influx in the brain cells is inhibited by domoic acid induced inhibition of
adenylate cyclase activity further reducing the cAMP level
➢ This Ca2+ overload induce toxicity in the neuronal cells leading to neurodegeneration
resulting in memory loss.xvi
D) Ibotenic acid-

➢ When delivered in the medial septum of rat, it causes degeneration of choline

acetyltransferase and acetylcholine esterase in the hippocampus and further
impaires memory performance
E) Ethanol –

➢ Acute ethanol administration decreases the specificity of place cells in rats in a

manner similar to that produced by lesions of the afferents of the hippocampal
system. xvii xviii
3. Transgenic models –

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 ➢ There are a series of transgenic mice models with abnormal genes expressing
mutant amyloid beta precursor protein (APP), which could produce amyloid plaques
and associated cognitive decline in the rodents.xix xx
➢ Other mice have mutations in genes for a protein called presenilin, but they do not
have amyloid deposition unless they have mutant APP genes
➢ Other strains of transgenic mice carry the genes that produce ApoE4
➢ Mutations in the APP gene sequence are linked to some familial forms of Alziemers
and induce A beta overproduction when expressed in transfected cultured cells
➢ A double transgenic mouse model with APP/PS1 mutation expressing human mutant
APP and mutant PS1 have shown spatial learning and memory decline followed by a
higher load of amyloid- beta protein and hyperphosphorylation of tau protein xxi xxii xxiii
4. Mechanical brain injury:

➢ Selective mechanical lesions induced to damage the hippocampal regions of

monkeys and rodents have been shown to impair cognitive performance.xxiv xxv

292
 Discuss the scope and techniques of Behavioural Medicine

DEFINITION:

Behavioural medicine was defined as “the interdisciplinary field concerned with the
development and integration of behavioural and biomedical science knowledge and
techniques relevant to health and illness and the application of this knowledge and these
techniques to prevention, diagnosis, treatment, and rehabilitation.” xxvi xxvii

HISTORY:

➢ In the early and mid-1960s behavioural therapy was applied to traditional mental
health problems
➢ Later, clinicians began to apply it to more medically related problems such as obesity
and smoking
➢ As the cardiovascular diseases and cancer emerged, in addition to a host of other
chronic diseases that had to be managed rather than cured, it was recognized that
behaviour played a major role in both the aetiology and maintenance of many of
these diseases, with cigarette smoking. xxviii xxix
➢ Finally, with the emergence technology which could be used in medical problems in
the form of biofeedback, behavioural medicine gained further importance
TECHNIQUES: xxx

A) “First Wave” Behaviour Therapy Treatment Strategies:

1. Progressive Muscle Relaxation:

➢ Relaxation therapy increases the parasympathetic nervous system activity and

hence, decreases the opposing sympathetic nervous system activity and arousal
➢ It can be used for stress and some medical disorders (headache, pain, postsurgical
distress)
2. Exposure Therapies- They are used to treat phobias

➢ Systematic desensitization consists of relaxation therapy and the presentation of

fear-producing stimuli arranged within a hierarchy
➢ It is based on the counterconditioning model that pairs a feared object with an
incompatible response
➢ Flooding is an exposure therapy that uses the extinction process to reduce anxiety. It
is based on the extinction model of habituation of the feared response
➢ The term extinction describes the process of decreasing fear and maladaptive
anxiety

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3. Aversion-Based Approaches:

➢ Used to treat sexual deviations and substance abuse, an aversive physical and/or
emotional state is paired with cues that elicit abusive behaviour or sexually deviant
behaviour
➢ Three types of stimuli have been used as aversive conditioning stimuli: chemical
aversion, electrical aversion (also called faradic aversion), and verbal aversion (also
known as covert sensitization)
4. Social Skills Training:

➢ It focuses on verbal and nonverbal behaviours like eye contact and speech latency
➢ It can be used with individuals need to learn how to interact with others
5. Contingency Management:

➢ It is based on principle of application of operant principles of reinforcement and

punishment in the process of behaviour change
B) “Second Wave” Behaviour Therapy Treatment Strategies

1. Cognitive Therapy- was given by Aaron Beck

➢ It is based on the premise that abnormal behaviour is the result of distorted

cognitive (mental) processes
➢ The other founding co-father of cognitive therapy was Albert Ellis, who developed
rational emotional behaviour therapy (REBT)
➢ In REBT, patients learn the A-B-C-model of psychological disturbance and
change
2. Problem-Solving Therapy:

➢ When patients are not able to approach a problem effectively, it teaches them the
skills necessary to discover effective solutions
3. Self-control therapies: It includes self-monitoring, self-evaluation and self-reinforcement

4. Habit reversal training (HRT):

It is designed to reduce repetitive behaviours (habits) such as hair pulling, stuttering, nail
biting, and tics

C) Third Wave” Behaviour Therapy Treatment Strategies

Behavioural Activation:

➢ It is based on the principle that increased activity is a necessary precursor towards

the reduction in depressed behaviour

2. Acceptance and Commitment Therapy:

➢ It is based on acceptance and mindfulness strategies, together with commitment and

behaviour change strategies, to increase psychological flexibility.
3. Mindfulness-Based Therapy:

➢ This integrates various techniques based on contemplation and meditation

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4. Dialectical Behaviour Therapy:

➢ It is based on the exchange and negotiation between therapist and patient, between
the rational and the emotional, and between acceptance and change
5. Cognitive Behavioural Analysis System of Psychotherapy:

➢ It is used for chronically depressed adults that combines components of cognitive,

behavioural, interpersonal, and psychodynamic therapies
SCOPE:

Indications:

1. Psychiatric disorders - anxiety, depression, substance use disorders, schizophrenia, and

bipolar disorder.

2. Psychological problems - marital discord, school refusal, and stress.

3. Medical problems - adjustment to chronic illness, medication adherence, and healthy

behaviours.

Limitations:

1. It requires a patient’s readiness to change and therefore, may not be appropriate for
patients who are not ready to change. The extent of patients’ readiness to change can be
identified and measured, and treatment approaches such as motivational interviewing have
been designed to help move patients toward readiness to change.

2. Also, in many places therapists with expertise are not available.

3. Ethical issues need to be considered in the use of aversion based techniques. These
procedures are used only as a last resort for very serious symptoms that have not
responded to alternative approaches. There also are ethical considerations in the use of
exposure treatment. If exposure sessions are not conducted appropriately, they can create
increased anxiety and cause harm.

295
 Human Sexual Response Cycle

Sexual Health Definition:

➢ According to the current working definition by the World Health Organisation (WHO,
2006a), sexual health is: “state of physical, emotional, mental and social well-being in
relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity
➢ Sexual health requires a positive and respectful approach to sexuality and sexual
relationships, as well as the possibility of having pleasurable and safe sexual
experiences, free of coercion, discrimination and violence
➢ The sexual rights of all persons must be respected, protected and fulfilled for sexual
health to be achieved and retained.”
➢ Human Sexual Response Cycle is a true psychophysiological experience
➢ Interactions between the psychosexual development, psychological attitude toward
sexuality, and attitudes toward one’s sexual partner are involved directly with the
physiology of human sexual response.xxxi
The human sexual response cycle is a four-stage model of physiological responses to
sexual stimulationxxxii

The phases of the cycle include: Desire, excitement phase, plateau, orgasm, and resolution.
This physiological response model was first formulated by William H. Masters and Virginia E.
Johnson in their 1966 book Human Sexual Responsexxxiii.

1. Desire- It consists of fantasies about and desire to have sexual activity.

2. Excitement/ Arousal phase- It consists of a subjective sense of pleasure and objective

signs of sexual excitement. It is brought on by psychological stimulation (fantasy or the
presence of a love object), physiological stimulation (stroking or kissing),or a combination of
the two.

3. Plateau phase- is the period of sexual excitement prior to orgasm.

4. Orgasm- This phase consists of peaking sexual pleasure, with release of sexual tension,
and rhythmic contraction of the perineal muscles and pelvic reproductive organs.

5. Resolution- In this phase, the muscles relax, and blood pressure drops. The refractory
period, is the time in which a man is unable to orgasm again, though women can also
experience a refractory period.

The phases in males and females are described further in detail.

Female Sexual Response Cycle:

1. Excitement/ Arousal phase

• Lasts several minutes to hours

• Sexual flush may be seen in the skin; maculopapular rash may originates on
abdomen and spread to anterior chest wall, face, and neck; can include shoulders
and forearms

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 • Breast-increase in size, congestion and areolar enlargement. Nipple erection may be
seen.
• Clitoris- increase in diameter of glans and shaft
• Labia majora- In nullipara: it elevates and flattens against perineum and in multipara:
congestion and edema is observed.
• Labia minora- increase in size, change to pink, red, deep red before orgasm seen
• Vagina- transudate starts appearing 10–30 sec after arousal, color changes to dark
purple; elongation and ballooning seen; lower third constricts before orgasm.
• Uterus- it ascends into false pelvis; labor-like contractions start just before orgasm
• Cervix- is passively elevated with uterus and swells in size
• Muscles- Myotonia
2. Orgasmic Phase

• Lasts 3–15 sec

• A well-developed flush is seen on the skin
• Breasts may become tremulous
• No change in Clitoris, Labia majora
• Labia minora- Contractions in the proximal part may be observed
• Vagina- contractions in lower one-third start occurring at intervals of 0.8 sec. they
may vary from 3-15
• Uterus- Contractions occur throughout the orgasm
• Rectum: Rhythmic contractions of sphincter occurs
• Hyperventilation and tachycardia is seen
• Muscles- Loss of voluntary muscular control
3. Resolution Phase

• lasts 10–15 min if orgasm occurs but if no orgasm then it may last upto 0.5 to 1 day
• Skin- Flush disappears in reverse order of appearance; perspiration on soles of feet
and palms of hands sometimes seen
• Clitoris -Shaft returns to normal position in 5–10 sec and detumescence occurs in 5–
30 min if orgasm occurs. If no orgasm occurs then detumescence may take several
hours
• Labia majora- In nullipara women, its size returns to normal in 1–2 min. In multipara,
return to normal size may take 10–15 min.
• Labia minora- returns to normal within 5 min
• Vagina- congestion disappears within a few seconds or, if no orgasm, in 20–30 min.
The ejaculate forms seminal pool in upper two-thirds of the vagina
• Uterus- contractions stop and it comes back to its normal position
• Cervix- its color and size return to normal, and it descends into the seminal pool
• Muscles Return to baseline status in seconds to minutes

Male Sexual Response Cycle

1. Excitement Phase

• It may last several minutes to hours; it heights before orgasm for 30 sec to 3 min.

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 • Skin- before orgasm, a sexual flush may appear; maculopapular rash may originate
on the abdomen and spread to anterior chest wall, face, and neck, and can include
shoulders and forearms
• Penis- vasocongestion of erectile bodies of corpus cavernosa of shaft causes
erection in 10–30 sec. The size of glans and diameter of penile shaft increases
further with increase in excitement. Loss of erection is seen if there is asexual
stimulus like loud noise and disturbance.
• Scrotum- Tightening and lifting of scrotal sac is seen
• Testes- elevation of testes and increase in size of testes
• Cowper’s glands- a few drops of mucoid fluid containing viable sperm are secreted
during excitement.
• Breasts- nipple erection may be seen before orgasm
• Muscles- Myotonia and contractions of facial, abdominal, and intercostal muscles
• Tachycardia: Up to 175 beats/min
• Blood pressure: increases by 20–80 mm systolic and 10–40 mm diastolic
• Respiration: Increased
2. Orgasmic Phase

• Lasts 3–15 sec

• Skin- a well-developed flush seen
• Penis- ejaculation occurs. Emission is marked by 3-4 contractions of 0.8 sec of
vas, seminal vesicles, prostate
Ejaculation is characterised by contractions of 0.8 sec of urethra and ejaculatory spurt of 12–
20 inch. at age 18 and this decreases with age
• No change is seen in Cowper’s glands, Scrotum and testes
• Muscles- Loss of voluntary muscular control
• Rectum: Rhythmic contractions of the anal sphincter
• Heart rate: Up to 180 beats/min (Tachycardia)
• Blood pressure: increases by 40–100 mm systolic and 20–50 mm diastolic
• Respiration: 40 respirations/min
3. Resolution Phase

• Lasts 10–15 min if orgasm occurs. If no orgasm then it lasts 0.5 to 1 day
• Skin- perspiration on soles of feet and palms of hands is seen. Flush disappears in
reverse order of appearance.
• Penis-Partial involution of erection happens in 5–10 sec with a variable refractory
period; full detumescence takes 5–30 min.
• Scrotum and testes- returns to baseline size because of loss of vasocongestion;
testicular and scrotal descent occurs 5–30 min after orgasm. Involution may take
several hours if no orgasm takes place.
• Muscles- Returns to baseline in 5–10 min

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299
 Internet use, abuse and addiction

Internet addiction disorder (IAD) or pathological Internet use, is a compulsive–impulsive

spectrum disorder that includes five primary types of addiction: xxxiv xxxv

1. Cybersexual Addiction
2. Cyber-Relational Addiction
3. Net Compulsions
4. Information Overload
5. Computer Addiction
Classification:

Currently, there is no recognition of internet addiction within the spectrum of addictive

disorders and, therefore, no corresponding diagnosis

It has, however, been proposed for inclusion in the next version of the Diagnostic and
Statistical Manual of Mental Disorder (DSM)

Epidemiology:

In India the number of internet users is expected to increase to 300 million and more in 2015
xxxvi
and among these about 72% of users are young adultsxxxvii.

Clinical features:

➢ Internet use disorder/ abuse is characterized by excessive or poorly controlled

preoccupations, urges, or behaviours related to internet use that leads to impairment
or distress
➢ It shares the characteristics of substance dependency like salience, mood
dysregulation, tolerance, withdrawal symptoms, and relapse.xxxviii
➢ It may operate on triggers or cues which lead to net binges as it provides emotional
relief, mental escape, and ways to avoid problems as do alcohol, drugs, food, or
gambling.
➢ Therefore, the origins for such net binges can be traced back to the following four
types of triggers which may be present- (a) applications, (b) feelings, (c) cognitions,
and (d) life events.
(a) Applications -We need to determine which applications are most problematic for the
addicted user. A thorough assessment should include an examination of the extent of use
among particular applicationsxxxix.

(b) Feelings- Internet use provides an artificial, temporary feeling of security or calm, of self-
worth or accomplishment, of power and control, or intimacy or belongingxl.

(c) Cognitions- maladaptive cognitions such as low self-worth, and depression trigger
pathological Internet use. Those who suffer from deeper psychological problems may be the
ones who are drawn the most to the anonymous interactive capabilities of the Internet in
order to overcome these problems.xli xlii

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d) Life events- individuals who are dissatisfied or upset by a particular area or multiple
areas of their lives have an increased likelihood of developing Internet addiction because
they don’t have alternative coping strategies. ix x

Co-morbiditiesxliii xliv

• Depression
• ADHD
• Impulse control disorders
• Alcohol abuse
• Social anxiety
• Depression and anxiety can also be part of withdrawal symptomsxlv.
Aetiology-

1. There has been evidence for involvement of specific serotonin genotype in internet
addiction and depression indicating similarities of neurochemical changes in both
disordersxlvi

2. People can use internet excessively for coping life stressors, loneliness and depression

3. People having social anxiety may use internet excessively to satisfy their needs to
socialize and overcome their anxiety for face to face interactions

4. Intra-family conflicts, and permissive or indulgent parenting

Negative effects:

1. It reduces people's motivation for interacting with each other, thereby causing them to
spend less time in the company of friends and family members with subsequent isolation
and depression

2. The parents and adolescents compete for using it and this adds to new struggles in the
family life leading to incompatibility and, a deterioration in the mental health and increasing
stress and isolationxlvii.

3. The increasing use of internet affected national and religious identity, self-identity, and
mental healthxlviii.

4. Sleep patterns are disrupted due to late night log-ins. In extreme cases, caffeine pills are
used to stay awake for longer sessions. Sleep deprivation causes fatigue, academic or
occupational impairment and decrease in immunity.

5. The sedentary act of computer use results in a lack of exercise and leads to an increased
risk for carpal tunnel syndrome, back strain, or eyestrain

6. There is a rise in divorce cases due to the online affairs.xlix

7. Students may have a decline in study habits, drop in grades or missing classes due to
excessive Internet use.

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Tests:

1. Internet Addiction Test (IAT) by Dr. Kimberly Youngl:

➢ Young’s Internet Addiction Test is a self-rated scale developed for screening and
measuring level of internet addiction and has been used extensively for this purpose
all over world
➢ It contains 20 questions related to internet usage to be scored on Likert scale from
1(rarely) to 5 (always)
➢ A total score of <20 represent normal user, between 20 to 49 represent mild
addiction, between 50 to 79 represent moderate addiction, between 80 to 100 severe
addiction
➢ Internet use to the point of addiction, however, can have wide-ranging consequences
that can affect personal, occupational, social, physical and psychological domains of
the individual’s life
➢ Serious relationship problems including conflicts in marriage and high rate of divorce
due to “cyber affairs‟ have been reported by various studiesli.
2. Internet-Related Problem Scale (IRPS)lii

➢ It was developed by Armstrong et al

➢ It is a 20-item scale comprising questions relating to tolerance, craving, and negative
impacts of Internet use
➢ It significantly correlated to the number of hours spent online and the MMPI-2
Addiction Potential Scale
Treatment:

1. Practicing the Opposite:

➢ A reorganization one’s time is a major part of treatment

➢ The aim is to have patients disrupt their normal routine and re-adapt new time
patterns of use and thus, break the habit
2. External Stoppers:

➢ The patient should use concrete things that the patient needs to do or places to go as
prompters to help log off
➢ Use of alarm clocks might help
3. Setting Goals:

➢ Many attempts to limit Internet usage fail because of ambiguous plans

➢ A proper schedule of Internet usage will give the patient a sense of being in control,
rather than allowing the Internet to take control

4. Reminder Cards:
The patient should make a list of the:
(a) five major problems caused by addiction to the Internet
(b) five major benefits for cutting down Internet use or abstaining from a particular
application
The patient should transfer the two lists onto a index card and take out the index card as a
reminder to reflect on the problems caused by their Internet overuse

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5. Support Groups:
➢ Recovery groups address the maladaptive cognitions and provide an
opportunity to build real life relationships that will release their social
inhibitions and need for Internet companionship
➢ These groups may help the Internet addict find real life support to cope with
difficult times during recovery similar to AA sponsors
6. Family Therapy:
➢ It is necessary among addicts whose marriages and family relationships have
been disrupted. Intervention should focus on several main areas:
(a) Educate the family on how addictive the Internet can be
(b) Reduce blame on the addict for behaviour’s
(c) Improve open communication about the pre-morbid problems in the family
which drove the addict to seek out psychological fulfilment of emotional
needs on-line
(d) Encourage the family to assist with the addict’s recovery such as finding
new hobbies, taking a long over-do vacation, or listening to the addict’s
feelings
➢ A strong sense of family support may enable the patient to recover from
Internet addiction.

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 Mind–body dualism

Definition:

➢ Mind–body dualism is the school of thought that believes that the mind and body are
distinct and separable.liii
➢ Mind and body dualism represents the metaphysical stance that mind and body are
two distinct substances, each with a different essential nature.liv
Historical Aspects:

➢ Its origin is credited to Rene Descartes of the 17th century

➢ In the ancient period, the prevalent orthodox Christian views of the mind-body
relationship had prevented the development of medical science
➢ According to them, human beings were spiritual beings and the body and soul were
one
➢ Diseases were ascribed to nonmaterial forces such as personal/collective wrong
doing
➢ Thus, mind-body dualism, demythologised body and handed over its study to
medicine and paved the way for progress in medical science through the study of
physiology and anatomy
➢ But, by isolating mind, this theory denied the significance of mind in individuals’
experience of health
➢ It took our attention away from the dynamic nature of human beings, their
relationship with the environment and also may have blocked the development of
effective interventions
lv
Types

1. Substance dualism - mind and matter are different kinds of foundations

2. Property dualism - distinction lies in the differences between properties of mind and
matter
3. Predicate dualism - the irreducibility of mental predicates to physical predicates
Substance dualism:

➢ It asserts that the mind can exist outside of the body, and the body cannot think by
itself
➢ They believe that immortal souls can occupy independent realms of existence
separate from that of the physical world
Property dualism:

➢ Differences lie in the properties of mind and matter, and that consciousness is
irreducible to neurobiology and physics
➢ It states that when matter is organized in the appropriate way (i.e., in the way that living
human bodies are organized), mental properties emerge
Predicate dualismlvi

➢ According to this theory, there can be no strict psycho-physical laws which connect
mental and physical events

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 ➢ Nevertheless, all mental events also have physical descriptions
➢ It is in terms of the latter that such events can be connected in law-like relations with
other physical events
➢ Mental predicates are irreducibly different in character (rational, holistic and
necessary) from physical predicates (contingent, atomic and causal)
Four varieties of dualist causal interaction:

1. Interactionism

➢ It is of the opinion that mental states, such as beliefs and desires, causally interact
with physical states
2. Non-reductive physicalism

➢ According to non-reductive physicalism all mental states are reducible to physical

states where mental properties map to physical properties and vice versa
3. Epiphenomenalism

➢ All mental events are caused by a physical event and have no physical
consequences and that one or more mental states do not have any influence on
physical states
➢ Mental phenomena themselves cause nothing further: they are causal dead-ends
4. Parallelismlvii

➢ This is of a view that mental causes only have mental effects and physical causes
only have physical effects
5. Occasionalismlviii

➢ It is school of thought which says that created substances cannot be efficient causes
of events
➢ Instead, all events are taken to be caused directly by God himself
➢ A material basis of interaction between material and immaterial was impossible and
therefore formulated his doctrine of occasionalism, stating that the interactions were
really caused by the intervention of God on each individual occasion
Arguments in favour:

1. The subjective argumentlix

➢ Minds perceive states differently from sensory phenomena and this cognitive
difference results in mental and physical phenomena having different properties
➢ This argument says that these properties are incompatible under a physical mind

Arguments against the concept:

1. Causal interaction:

➢ If consciousness (the mind) can exist independently of physical reality (the brain),
one must explain how physical memories are created in connection with
consciousness
➢ One of the main objections to dualistic interactionism is lack of explanation of how
the material and immaterial are able to interact

305
2. The argument from physics:

➢ Any action of a nonphysical mind on the brain would be the violation of physical laws,
such as the conservation of energy.lx
3. Argument from brain damage:

➢ In instances of brain damage caused by automobile accidents, drug abuse,

pathological diseases, etc., the mental substance and/or properties of the person are
notably changed or compromised
➢ It is further supported by data from the effects of neuro-active chemicals (such as
those affecting neurotransmitters) on mental functions and from research on
neurostimulation (direct electrical stimulation of the brain, including transcranial
magnetic stimulation) lxi lxii
4. Argument from biological development:

➢ Human beings, both phylogenetically and ontogenetically start their existence as

completely physical or material entities and nothing outside of the domain of the
physical is added later on in the course of development
➢ There is nothing non-material or mentalistic involved in conception, the formation of
the blastula, the gastrula etc.lxiii
5. Argument from neuroscience:

➢ Sometimes the decisions taken by a person can be detected up to 10 seconds in

advance by means of scanning their brain activity
➢ Moreover, subjective experiences, mental imagery and covert attitudes can be
detected
➢ There is robust evidence that cognitive processes have a physical basis in the brain.
lxiv lxv

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 Operant Conditioning

Introduction:

➢ Learning can occur through various means. A few of them include classical
conditioning, operant conditioning, cognitive learning etc.
Classical/Respondent/Pavlovian conditioning:

➢ Given by Ivan P Pavlov is a process in which one learns to link two or more stimuli
and anticipate events
➢ It is a learning process in which a neutral stimulus becomes associated with a
meaningful stimulus and acquires the capacity to elicit a similar response

Operant/Instrumental Conditioning given by B. F. Skinner is a process in which an

individual changes behaviour because of the consequences of the behaviour

Principles of operant conditioning:

➢ Reinforcer and punishment are the core tools through which operant conditioning
works.
➢ Reinforcer: An environmental event that is the consequence of an instrumental
response and that makes the response more likely to occur again.
➢ Punishment: An environmental event that is the consequence of an instrumental
response and that makes the response less likely to occur again.

The changes in behaviour due to operant conditioning can have the following
consequences:

1. Positive reinforcement:

➢ This occurs when a behaviour (response) is followed by another stimulus that is

rewarding, increasing the frequency of that behaviour
➢ For example, if a rat in a Skinner box gets food when it presses a lever, its rate of
pressing will go up

2. Negative reinforcement (Escape learning /Avoidance learning):

➢ This occurs when behaviour (response) is followed by the removal of an aversive

stimulus, thereby increasing that behaviour's frequency
➢ In the Skinner box experiment, the aversive stimulus might be a loud noise
continuously sounding inside the box; negative reinforcement would happen when
the rat presses a lever, turning off the noise

3. Positive punishment:

➢ This occurs when a behaviour (response) is followed by an aversive stimulus, such

as pain from a spanking, which results in a decrease in that behaviour

4. Omission of reinforcement:

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 ➢ Occurs when a behaviour (response) is followed by the removal of a stimulus, such
as taking away a child's toy following an undesired behaviour, resulting in a decrease
in that behaviour

5.Extinction:

➢ This occurs when a behaviour (response) that had previously been reinforced is no
longer effective as no stimulus is being provided
➢ For example, a rat is first given food many times for lever presses. Then, in
"extinction", no food is given. Typically the rat continues to press more and more
slowly and eventually stops, at which time lever pressing is said to be "extinguished."

Schedules of reinforcement lxvilxvii:

Schedules of reinforcement are rules that control the delivery of reinforcement. The rules
specify either the time that reinforcement is to be made available, or the number of
responses to be made, or both

The following are the most basic and commonly used:

1. Fixed interval schedule:

➢ Reinforcement occurs following the first response after a fixed time has elapsed after
the previous reinforcement
➢ The organism typically pauses after reinforcement, and then begins to respond
rapidly as the time for the next reinforcement approaches
2. Variable interval schedule:

➢ Reinforcement occurs following the first response after a variable time has elapsed
from the previous reinforcement
➢ This schedule typically yields a relatively steady rate of response that varies with the
average time between reinforcements

3. Fixed ratio schedule:

➢ Reinforcement occurs after a fixed number of responses have been emitted since the
previous reinforcement
➢ An organism trained on this schedule typically pauses for a while after a
reinforcement and then responds at a high rate
➢ If the response requirement is low, there may be no pause; if the response
requirement is high the organism may quit responding altogether

4. Variable ratio schedule:

➢ Reinforcement occurs after a variable number of responses have been emitted since
the previous reinforcement
➢ This schedule typically yields a very high, persistent rate of response

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5. Continuous reinforcement:

➢ Reinforcement occurs after each response

➢ Organisms typically respond as rapidly as they can, given the time taken to obtain
and consume reinforcement, until they are satiated.

Factors affecting Effectiveness i lxviii:

1. Satiation/Deprivation:

➢ The effectiveness of a stimulus will be reduced if the individual has received enough
of that stimulus to satisfy its appetite
➢ The opposite effect will occur if the individual becomes deprived of that stimulus: the
effectiveness of a consequence will then increase
➢ If someone is not hungry, food will not be an effective reinforcer for behaviour.lxix

2. Immediacy:

➢ An immediate consequence is more effective than a delayed consequence

➢ If one gives a dog a treat for "sitting" right away, the dog will learn faster than if the
treat is given later

3. Contingency:

➢ To be most effective, reinforcement should occur consistently after responses and

not at other times

4. Size:

➢ The size, or amount, of a stimulus often affects its potency as a reinforcer. Humans
and animals engage in a sort of "cost-benefit" analysis
➢ A tiny amount of food may not "be worth" an effortful lever press for a rat
➢ A pile of quarters from a slot machine may keep a gambler pulling the lever longer
than a single quarter

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The learnt behaviour has the following characteristics:

1. Discrimination:

➢ Typically occurs when a response is reinforced only in the presence of a specific

stimulus
➢ For example, a pigeon might be fed for pecking at a red light and not at a green light;
in consequence, it pecks at red and stops pecking at green

2. Generalization:

➢ It is the tendency to respond to stimuli that are similar to a previously trained

discriminative stimulus
➢ For example, having been trained to peck at "red" a pigeon might also peck at "pink",
though usually less strongly

3. Context:

➢ Refers to stimuli that are continuously present in a situation, like the walls, tables,
chairs, etc. in a room, or the interior of an operant conditioning chamber
➢ This may cause difficulties for behavioural therapy, because behaviours learned in
the therapeutic setting may fail to occur elsewhere

Applications:

1. Programmed learning- the material to be learnt is broken down into small

steps and feedback after each step acts as a reinforcement

2. Omission training/Time out- For teaching appropriate child behaviors in

parent management training.

3. Differential reinforcement - is the implementation of reinforcing only the

appropriate response (or behavior you wish to increase) and applying
extinction to all other responses.

4. Shaping -We identify the desired target behavior. The form of this behavior is
then gradually changed across successive trials by reinforcing behaviors that
approximate the target behavior more and more closely. When the target
behavior is finally emitted, it may be strengthened and maintained by the use
of a schedule of reinforcement

5. The Personalized System of Instruction-It is composed of small self-paced

m units of modules. Unit tests are given after each module and learners must
show mastery of each unit before proceeding further. It combines mastery
learning with principles of reinforcement.

6. Token economy- The reinforcers are symbols or "tokens" that can be

collected over time and exchanged for other rewards. It is used to in patients
of schizophrenia and developmental disorders.

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 Role of biological, genetic and psychological factors in the
development of personality

Definition:

Personality is the enduring pattern of feelings, thoughts, and behaviours that differentiate
human being from one another.lxx

Evolution:

The evolutionary process of natural selection has been suggested to explain variations in
personality.lxxi It chose traits which were the most useful. Many opposing personality traits
proved to be advantageous in different ways. lxxii

Influencing factors:

Personality is influenced by genetic, environmental, psychological factors and many other

factors.lxxiii

1. Genetics:

The following factors point towards the role of genetics in personality

(1) Approximately 50% of variation in observable personality traits is attributable to genetic

influences. A given genotype may lead to a phenotype under the right environmental
circumstances.lxxiv

(2) Infant temperament is believed to have a basis in adult personality.lxxv

(3) The Five Factor Model of personality suggests that differences in levels of the five
personality traits i.e. neuroticism, extraversion, openness to experience, agreeableness, and
conscientiousness are present from early times of our life.lxxvi

(4) Classic theories of personality, such as Freud’s tripartite theory, and post-Freudian
theory, including developmental stage theories and type theories, have often suggested that
personality development occurs in childhood.

(5) The polymorphisms and sequence repeats in the gene for dopamine receptor D4 and
serotonin transporter gene 5-HTTLPR, have both been found to influence the extraversion
trait in adults. lxxvii

(6) Another point which suggests role of genetics is that Schizotypal Personality Disorder
tends to be more frequent in families where at least one family member has been previously
diagnosed with Schizophrenia.lxxviii Hence personality disorders are also found to have a
genetic basis.

311
2. Biological:

The case of Phineas Gage is one of the earliest examples of biological bases of personality.
In an 1848 accident, a large iron rod was driven through Gage's head, and as a result his
personality changed.lxxix Researchers now use electroencephalography (EEG), positron
emission tomography (PET), and functional magnetic resonance imaging (fMRI to help
localize personality traits in the brain. The following are some of the findings of biological
basis of personality-

(1) Neurotransmitters:

Dopamine and Serotonin pathways- involves the autonomic nervous system, fear-
processing circuits in the amygdala, the reward pathway from the ventral tegmental area
(VTA) to the nucleus accumbens and prefrontal cortex.

Dopamine:

• It promotes exploratory behaviour.lxxx

• Dopaminergic pathways are associated with extraversion trait of the Five Factor
Model of Personality.lxxxi
• The monoamine oxidase (MAO) enzyme which has a preferential affinity for
dopamine, and its levels are inversely correlated with sensation seeking.lxxxii
Serotonin:

• It promotes avoidance behaviour through inhibitory pathways xi.

• It is associated with Neuroticism, Agreeableness, and Conscientiousness of the Five
Factor Model of Personality

(2) Synaptic plasticity:

wherein the amygdala and hippocampus of the limbic system mediate emotional intensity
and consolidate memory of experiences

The brain learns from these experiences, retain memories, and ultimately maintain
personality.lxxxiii

(3) Personality theories with biological basis:

1. Eysenck's three-factor model of personality:

1. Extraversion (E) – degree to which people are outgoing and are

interactive with people, is mediated by the activation of the reticular
formation.
2. Neuroticism (N) – degree of emotional instability is associated with the
limbic system.
3. Psychoticism (P) – degree of aggression and interpersonal hostility.
2. Gray's reinforcement sensitivity theory:

312
 ➢ It is based on the idea that there are three brain systems that all differently
respond to rewarding and punishing stimuli.lxxxiv
➢ Fight-flight-freeze system- mediates the emotion of fear. The personality traits
associated with this system is fear-proneness and avoidance.
➢ Behavioural inhibition system – mediates the emotion of anxiety. The
personality traits associated with this system is worry-proneness and anxiety.
➢ Behavioural approach system – mediates the emotion of anticipatory pleasure
from reactions to desirable stimuli. The personality traits associated with this
system are optimism, reward-orientation, and impulsivity.
3. Cloninger's biological dimensions of personality:

➢ This model of personality is based on the idea that different responses to punishing,
rewarding, and novel stimuli is caused by an interaction of the three dimensions
below:
1. Novelty Seeking – Degree to which people are impulsive correlated with
low dopamine activity.
2. Harm Avoidance – Degree to which people are anxious, correlated with
high serotonin activity.
3. Reward Dependence – degree to which people are approval seeking,
correlated with low norepinephrine activity.
➢ Novelty Seeking correlated with increased grey matter volume in regions of
the cingulate cortex
➢ Harm Avoidance correlated with decreased grey matter volume in the
orbitofrontal, occipital, and parietal cortex
➢ Reward Dependence correlated with decreased grey matter volume in the
caudate nucleus.lxxxv
4. Five factor model of personality:

➢ There is correlation between the volumes of certain brain areas with each of
the five traits in the Five Factor Model.
1. Openness -did not have any significant correlation with the volume of any
brain structures.
2. Conscientiousness - increased volume in the lateral prefrontal cortex, a
region involved in planning and the voluntary control of behaviour.
3. Extraversion - with increased volume of medial orbitofrontal cortex, a
region involved in processing reward information.
4. Agreeableness - with increased volume in regions that process
information about the intentions and mental states of other individuals.
5. Neuroticism - with increased volume of brain regions associated with
threat, punishment, and negative emotions.lxxxvi

3. Psychological Factors:

The following are the psychological theories of personality development:

(1) Psychoanalytic theories:

➢ Freud proposed five psychosexual stages of personality development

313
 ➢ It stated that adult personality is dependent upon early childhood experiences and
largely determined by age five
➢ Fixations that develop during the infantile stage contribute to adult personality and
behaviour.lxxxvii
➢ Alfred Adler believed birth order may influence personality development
➢ Heinz Kohut used narcissism as a model of how people develop their sense of self
➢ Karen Horney gave the theory of the "real self" and the "ideal self
The "real self" is how humans act with regard to personality, values, and morals; but the
"ideal self" is a construct individual implement in order to conform to social and personal
norms.
(2) Behaviourist theories:

➢ This school of thought developed by B. F. Skinner, analyses the behavioural aspect

of personality through learning-conditioning
➢ Richard Herrnstein extended this theory by accounting for attitudes and traits which
develops as the response strength in the presences of a group of stimuli becomes
stable.lxxxviii
(3) Humanistic theories:

➢ Abraham Maslow gave believed persons interested in growth move towards self-
actualizing
➢ Characteristics of self-actualizers according to Maslow include the four key
dimensions:
1. Awareness
2. Reality and problem centered
3. Acceptance/Spontaneity
4. Unhostile sense of humour/democratic.lxxxix
➢ Carl Rogers tried to model a particular approach to therapy takes the client's
viewpoint and reflects back their feeling and the context for it
(4) Social cognitive theories:

➢ Cognitive-Experiential Self-Theory by Seymour Epstein, argues that humans

operate by way of two independent information processing systems: experiential
system and rational system
o The experiential system is fast and emotion-driven
o The rational system is slow and logic-driven
o These two systems interact to determine our personality.xc
➢ Attributional style theory builds upon locus of control and states that we also need
to consider whether people attribute to stable causes or variable causes, and to
global causes or specific causes.xci
➢ Personal construct psychology by George Kelly is based on the view that people
employ systems for construing the world that are distorted by idiosyncratic
experiences not applicable to their current social situation.xcii

314
 Sensory deprivation

Definition:

➢ Sensory deprivation or perceptual isolation is the deliberate reduction or removal of

stimuli from one or more of the senses
History:

➢ Sensory deprivation techniques were used by some of the armed forces, as a means
of interrogating prisoners.xciii
➢ The European Court of Human Rights ruled that the use of the five techniques by
British security forces in Northern Ireland amounted to a practice of inhumane and
degrading treatment
➢ In the 1950s, sensory deprivation experiments were conducted to determine the
effects of restricted environmental stimulation on mental and physical functions
➢ For 24 hours a day, students were confined to a bed in cramped cubicles with their
vision and hearing blocked by various means, such as opaque goggles and U-
shaped pillows around their heads
➢ The students' physical and psychological functions quickly deteriorated under these
harsh conditions
Methods:

➢ It can be achieved by-Simple devices such as blindfolds or hoods and earmuffs can
cut off sight and hearing, while more complex devices can also cut off the sense of
smell, touch, taste, thermoception (heat-sense), and 'gravity'.
➢ There are two basic methods of Restricted Environmental Stimulation Therapy
(REST): chamber REST and flotation REST.
1. In chamber REST, the subject lies on a bed in a completely dark and sound-reducing (on
average, 80 dB) room for up to 24 hours.

2. Flotation REST- An isolation tank, usually called a sensory deprivation tank (also known
as float tank, flotation tank, or sensory attenuation tank) is a lightless, soundproof tank filled
with salt water at skin temperature, in which individuals float.

Effects:

1. Short-term sessions- causes relaxtion

2. For the first 40 minutes, it is reportedly possible to experience itching in various parts of
the body (a phenomenon also reported to be common during the early stages of meditation)

3. The last 20 minutes often end with a transition from beta or alpha brainwaves to theta,
which typically occur briefly before sleep and again at waking. In a float tank, the theta state
can last for several minutes without the subject losing consciousness. Some use the
extended theta state as a tool for enhanced creativity and problem solving.

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4. The relaxed state also involves lowered blood pressure, lowered levels of cortisol, and
maximal blood flow. Apart from physiological effects, REST seems to have positive effects
on well-being and performance.xciv

5. Extended or forced sensory deprivation can result in extreme anxiety, hallucinations,

bizarre thoughts, and depression.xcv xcvi

6. Ganzfeld effect:

➢ A constant uniform stimulus is used instead of attempting to remove the stimuli; this
leads to effects which have similarities to sensory deprivation.xcvii
➢ It has been most studied with vision by staring at an undifferentiated and uniform field
of colour
➢ The visual effect is described as the loss of vision as the brain cuts off the
unchanging signal from the eyes
➢ The result is seeing black, an apparent sense of blindness
➢ A flickering ganzfeld causes geometrical patterns and colours to appear
➢ The ganzfeld effect can also elicit hallucinatory percepts in many people, in addition
to an altered state of consciousness.xcviii
7. Schizophrenics appear to tend to experience less hallucinations while in REST as
compared to healthy individuals. A possible explanation for this could be that healthy
individuals are normally exposed to a greater degree of sensory stimulation in everyday life,
and in REST, the brain attempts to re-create a similar level of stimulation, producing the
hallucinatory events the main findings were significant decreased experienced stress, worst
pain, anxiety, and depression - as well as significant increased sleep quality and optimism
for the flotation-REST group compared to the control group.

8. Transient depersonalization can occur. It can alter an individual’s state of consciousness,

producing prominent dissociative symptoms.

9. It causes changes in hypnotizability, after which the degree of hypnotizability returns to

baseline for most individuals.

Uses:

1. Sensory deprivation has been used in various alternative medicines and in psychological
experiments (e.g., with an isolation tank). Flotation is widely advertised as a form of
alternative medicine with claims that it has beneficial health effects.

2. Its use has been explored in aiding in the cessation of smoking. When combined with
other effective smoking cessation methods (for example: behaviour modification) resulted in
long-term abstinence. xcix

3. Alcoholism has also been the target of research. In conjunction with anti-alcohol
educational messages, patients who underwent two hours of REST treatment reduced
alcohol consumption.

4. It has been tested to determine its effect on users of other drugs.c

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Precautions:

➢ People suffering from high blood pressure, heart disease, or kidney conditions should
consult a physician or family doctor before undergoing this procedure
➢ Those who have claustrophobia, certain psychological disorders, or discomfort in the
dark may find the treatment unpleasant

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 Tests of Formal thought disorder / Discuss the various approaches to
the assessment of thought disorders in Psychiatry

Definition:

Thought disorder is a multidimensional impairment involving disturbances of thought,

language processing, and social cognition.ci

Subtypes of thought disorders-cii

➢ Thought disorders are of 2 subtypes:

1. Disorders of thought form
2. Disorders of thought content
➢ Disorders of thought form are defined by lack of organizing thought in a definite
logical sequence to reach a certain goal
➢ Delusions, obsessions etc are considered within disorders of thought content
➢ Disorders of thought form can be further subdivided in 2 subgroups:
1. Negative/alogia meaning poverty of speech and decrease in content of speech
2. Positive includes derailment, loss of goal, poverty of content and tangentiality
Disorders of the form of the thought:

1. Poverty of Speech (Poverty of Thought, Laconic Speech)- Restriction in the amount of

spontaneous speech, so that replies to questions tend to be brief and cannot be elaborated.

2. Poverty of Content of Speech (Poverty of Thought, Empty Speech, Alogia, Negative

Formal Thought Disorder)- wherein the patient has spoken at some length but has not given
adequate information to answer the question.

3. Pressure of Speech-An increase in the amount of spontaneous speech as compared

with what is considered ordinary or socially customary.

4. Distractible Speech- the patient repeatedly stops talking in the middle of a sentence or
idea and changes the subject in response to a nearby stimulus, such as an object on a desk,
the interviewer's clothing or appearance, etc.

5. Tangentiality- Replying to a question in an oblique, tangential, or even irrelevant manner.

The reply may be related to the question in some distant way.

6. Derailment (Loose Associations, Flight of Ideas)-A pattern of spontaneous speech in

which the ideas slip off the track onto another one that is clearly but obliquely related, or onto
one that is completely unrelated.

7. Incoherence (Word Salad, Jargon Aphasia, Schizophasia, Paragrammatism)- it is a

pattern of speech that is incomprehensible at times. At times, the rules of grammar and
syntax may be ignored, and a series of words or phrases may be joined together arbitrarily
and at random. The disturbance may appear to be at a semantic level, so that words are
substituted in a phrase or sentence so that the meaning seems to be distorted or destroyed;
the word choice may seem totally random or may appear to have some oblique connection
with the context.

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8. Clanging: it is a pattern of speech where sounds rather than meaningful relationships
appear to govern word choice, so that the intelligibility of the speech is impaired and
redundant words are introduced. This pattern of speech may also include rhyming
relationships and punning associations, so that a word similar in sound brings in a new
thought.

9. Neologisms: New word formations. A neologism is defined here as a completely new

word or phrase whose derivation cannot be understood.

10. Word Approximations (Paraphasia, Metonyms): Old words that are used in a new
and unconventional way, or new words that are developed by conventional rules of word
formation. Here, the meaning will be evident even though the usage seems peculiar or
bizarre (ie, gloves referred to as "handshoes," a ballpoint pen referred to as "paperskate,"

etc).

11. Circumstantiality: It is a pattern of speech that is indirect and delayed in reaching its
goal idea. The patient brings in many tedious details and makes parenthetical remarks.
Circumstantial replies or statements may last for many minutes if the speaker is not
interrupted and urged to get to the point.

12. Loss of Goal: It is a failure to follow a chain of thought through to its natural conclusion.
The speech begins with a particular subject, wanders away from the subject, and never
returns to it. The patient may or may not be aware that he has lost his goal. This often
occurs in association with derailment.

13. Perseveration-is a persistent repetition of words, ideas, or subjects so that, once a

patient begins a particular subject or uses a particular word, he continually returns to it in the
process of speaking.

14. Echolalia: A pattern of speech in which the patient echoes words or phrases of the
interviewer. It tends to be repetitive and persistent.

15. Blocking: It is the interruption of a train of speech before a thought or idea has been
completed. The person says that he cannot recall what he had been saying or meant to say.

Scales to evaluate thought disorders:

1. Thought, Language and Communication Scale:

➢ It was developed by Andreasen and includes definitions of 18 subtypes of disorders

of thought
➢ Likert type scale is used with interval of 0 (none) — 3 or 0 — 4 for rating severity,
depending on the item, is used for evaluation
➢ This scale categorizes poverty of speech, poverty of content of speech, pressure of
speech, distractible speech, tangentiality, derailment, incoherence, illogicality,
clanging, neologisms, word approximations, circumstantiality, loss of goal,
perseveration, echolalia, blocking, stilted speech and self-reference items as thought
disorders
➢ A standard structured 45-minute interview is used for ratings

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 ➢ However, it is not sensitive for subtle thought disorders seen in relatives of patients
with schizophrenia.ciii civ
2. Thought Disorder Index:

➢ It was developed by Johnston and Holzman in 1979

➢ Rorschach cards and verbal subscales of Wechsler Adult Intelligence Test (WAIS)
are used for assessment
➢ The scale includes 23 categories: Inappropriate distance, flippant response,
vagueness, peculiar verbalizations and responses, word-finding difficulty, clangs,
perseveration, incongruous combinations, relationship verbalization, idiosyncratic
symbolism, queer responses, confusion, looseness, fabulized combinations, playful
confabulation, fragmentation, fluidity, absurd responses, confabulations, autistic
logic, contamination, incoherence, neologisms
➢ The disadvantage of this scale is that it is time consuming for routine use requiring
extensive education for grading.iv
3. Bizarre-Idiosyncratic Thinking scale:

➢ This scale has 5 categories: Linguistic form and structure, content of the statement
(ideas expressed), what is intermixed into the response, relationship between
question and esponse, behaviour
➢ The Comprehension Subtest of the WAIS or WAIS-R, Gorham Proverbs Test and
other verbal tests such as Rorschach Test or free-verbalization situations are also
used for assessment.cv
4. The Thought and Language Index (TLI):

➢ Participant is required to produce eight one-minute speech samples in response to

the eight standard pictures taken from the Thematic Apperception Test
➢ It comprises impoverishment of thought and disorganization of thought subscales
➢ Impoverishment of thought subscale consists of three items: Poverty of speech,
weakening of goal and perseveration
➢ Disorganization of thought subscale includes five items: Looseness, peculiar word
use, peculiar sentence construction, peculiar logic and distractibility
➢ The entire interview is recorded on audiotape and then transcribed.cvi
5. Formal Thought Disorder (FTD) Scales:

➢ It has two subtypes-one for patients (FTD-patient) and one for carers (FTD-carer)
➢ FTD-patient includes 29 items and FTD-carer consists of 33 items
➢ FTD-patient items are responded to by the patient as “yes/no” subjectively
➢ Responses are graded as 2 (extraordinary response) and 1 (ordinary response)
➢ FTD-carer items are replied to by the caregiver of the patient as “never, sometimes,
often and almost anytime” subjectively
➢ Responses are evaluated between scores of 1–4.cvii
6. Thought and Language Disorder (TALD) scale:

➢ It evaluates objectively observed symptoms and subjective phenomena

➢ The scale consists of 30 items
➢ Items are loaded under four factors: Objective positive, subjective negative, objective
negative and subjective positive
➢ The clinical interview consists of two parts

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➢ In the first part, the person is asked about general topics (daily life, hobbies etc.), and
in the second part, semi-structured questions are asked
➢ While objective evaluation of the scale is carried out through the interview, the
subjective evaluation is limited by the previous 24 hour period before the interview
➢ Severity of FTD is rated from 0 (not present) to 4 (severe).cviii

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 Aggression predictors of aggression? Psychological and social
theories of aggression

Definitions:

Aggression may be defined as any behaviour with the intention to harm another person who is
motivated to avoid that harmcix cx. It is an overt behaviour that involves threat or action that may
cause pain, withdrawal, or loss of resources. Violence can be defined as a physically or
psychologically harmful human aggression that involves the threat or use of forcecxi.

Predictors:

1. Patterns of infantile attachment:

➢ Disorganized attachment characterized by inconsistent responses to separation

stress is predictive of aggression
2. Impulsivity and inattention in preschool years may predict aggression at a later age. Opposition
and hyperactivity increases the likelihood of aggression.

3. Development and Stability:

➢ Physical aggression peaks in the toddler years and then decreases but the
degree to which one person is aggressive relative to others of the same age is
fairly stable across the life. cxii
4. Large body size, stimulus seeking, and fearlessness at the age of 3 years predicted aggression at
the age of 11 years.

5. Gender Differences- males are found to be more aggressive than females.

6. Trait anger-is extreme sensitivity to provocation and an increased inclination to respond with
aggression once provoked.

7. Impulsivity and Self-Control

➢ Impulsive people have difficulty stopping aggressive impulses. People will be less
aggressive if they have greater control over their emotions, greater self-control,
and a stronger capacity to inhibit their impulses.cxiii
8. Intelligence

➢ There may be link between low IQ and higher levels of aggression in children,
particularly in children with poor verbal intelligence and/or with low self-control.
9. Hormones:

(1)The hormone most consistently linked with aggression is testosterone. Testosterone’s effect on
aggression is a by-product of its effect on dominance.

(2)Low levels of oestrogen and progesterone may be associated with aggression.

(3)Low levels of oxytocin may be linked with increased aggression.

10. Genetic Predispositions

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The two genetic markers of aggression are a polymorphism in the promoter of the monoamine
oxidase A gene (MAOA) and a variation in the 5-HT serotonin transporter gene.

(1) MAOA gene polymorphism -aggression and antisocial behaviour are most likely in those children
who have this genetic trait and experience childhood maltreatment.cxiv

11. Environment and Cues:

(1)Provocation- is a trigger for aggression. It can either be direct or indirect like social exclusion,
having rumours spread about them.cxv

(2)Weapons

People who view a real or virtual weapon tend to have aggression-related cognitions primed in their
semantic memory, and are more likely to behave aggressively. This effect varies by type of weapon
and hunting experience.

(3)Violent Environment

This social cognitive model states that people who are exposed to violence have an associative
neural network with aggression-related knowledge structures. People exposed to violent
environments, whether homes, neighbourhoods, or countries, have a greater predisposition to be
aggressive.cxvi

(4) Violent Media

The same principle applies to exposure to violent media. It causes desensitization to violence in both
the short- and long-term.cxvii

It has been linked to hostile thinking, increase in aggressive thoughts and feelings, and decreases in
empathy and prosocial behaviour.cxviii

(5) Environmental Stressors

Physical pain, bad-smelling odors, loud or aversive noises, and hot temperatures can increase
aggression especially if the individual has no control over those environmental stressors.

(6) Anonymity

It is much easier to hurt another if an individual believes there will be no consequences, and
anonymity allows a person to experience ‘deindividuation’ – a lessening of the restraints on
antisocial behavior normally accorded to people perceived as being ‘individuals.’

(7) Social Rejection

The response to social rejection may be aggression in situations where the person cannot do
anything about the rejection without causing major retaliations.cxix

(8) Substances

Alcohol intoxication is linked with murders, assaults, rapes, and intimate partner violence. This may
be due to a diminished ability to inhibit their aggressive impulses.cxx

Other substances like stimulants, amphetamines, and methamphetamines which cause disinhibition
and/or an increase in physiological arousal may lead to aggression.

12. Emotion/Affect

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Aggression may be caused by negative emotions like anger, shame, jealousy, and frustration. Anger
increases aggression by reducing inhibitions, narrowing focus to cues for aggression, and alerting
people to cues for potential threats. Jealousy has been linked with aggression in cases with intimate
partner violence.

Emotions protective for aggression are empathy-taking another person’s perspective and having
concern for them.

13. Behavioural inhibition-the tendency to react fearfully to strange persons or novel situations
reduces the likelihood of aggression.

14. Cognitive markers include (1) hostile attribution bias, wherein the person misinterprets neutral
stimuli as threat, and (2) lower-than-age-appropriate problem-solving skills in which nonaggressive
options fail to be considered.

15.Physiological traits of autonomic hypoarousal, with lower resting heart rate, decreased heart rate
reactivity, and less skin conductance reactivity to stress have also been associated with increased
rates of aggression.

16. Biomarkers for aggression: prolactin response to fenfluramine, a marker of central serotonin
activity, was reduced in children and adults with aggression.

Psychological Theories Of Aggression:

1. Personality Traits:

The three personality types- psychopathy, Machiavellianism, and narcissism are linked with high
levels of aggression, lack of empathy, and decreased emotional responding

(1) Psychopaths, especially those with secondary psychopathy characteristics, are often impulsive,
fearless, and unconcerned about negative consequences to themselves or others

(2) Narcissists respond aggressively when they feel threatened particularly by insults, humiliations,
or other threats to their inflated ego, or when they fear that their flaws may be exposed

(3) Machiavellians use aggression to achieve their goals and feel little or no remorse when harming
others. They consider potential consequences to themselves, and are thus more likely to aggress
indirectly so that they are not held responsible for their actions

2. The ‘Big Five’ Personality Traits- people low in agreeableness and high in neuroticism are more
aggressive and violent.cxxi

3. Arousal: Cognitive Labelling and Excitation Transfer theorycxxii

➢ It states that if two arousing events are separated by a short amount of time then
the arousal from the first event will add to arousal of the second(Cognitive
Labeling).
➢ This leads to a person becoming angry to a level far greater than might be
expected from a minor provocation (Excitation Transfer theory).
4. Cognitive Neoassociation Theorycxxiii

➢ According to this theory, unpleasant experiences produce a negative affect, which is

linked to thoughts, feelings, and behavioural tendencies that are in turn linked to fight
and flight tendencies

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 ➢ If a person has a dominant ‘fight’ response then most of the situations are more likely
to elicit aggression in that person

Social Theories Of Aggression:

1. The Frustration-Aggression Hypothesis:

➢ States that frustration is caused when a goal is blocked
➢ It suggested that “the occurrence of aggressive behaviour always
presupposes the existence of frustration,” and that “the existence of
frustration always leads to some form of aggressioncxxiv”.

2. Social Learning Theory:

➢ Given by Bandura states that the potential for aggression is biological, but the
expression of aggression is learnt through observation
➢ The person observes aggressive behaviour in a model and imitates this
behaviour
➢ Imitation is stronger if they identify with or admire the model, or if the model is
rewarded or succeeds. This is vicarious reinforcement
➢ For social learning to take place, a child must form a mental representation of
the event which includes the possible rewards or punishments for behaviour
➢ When a child imitates an aggressive behaviour, the outcome of this behaviour
influences the value of aggression for the child
➢ If they are rewarded, they are likely to repeat the behaviour
➢ Later these children develop self-efficacy, which is confidence in their ability
to carry out aggressive actions
➢ If aggressive behaviours are unsuccessful, they will have a low sense of self-
efficacy and will not continue the behaviour

3. Social Information Processing (SIP) theorycxxv

➢ It is based on the “hostile attributional bias” which is the tendency to interpret
ambiguous events like being bumped in a corridor, as being motivated by hostile
intent.
4. Script theory cxxvi
➢ Here the “scripts” mean a particular situation and a guide for how to behave in
them, learnt through direct experience or observational learning
➢ If a person repeatedly responds to conflict by using scripts that include behaving
aggressively, these scripts may become chronically accessible to mind
➢ Later, it is generalized to other situations, which increases the likelihood of
aggression to occur in those situations

5. The General Aggression Model:

➢ Aggression in a person depends on their characteristics like biology, genes,
personality, attitudes, beliefs, behavioural scripts and environmental trigger
such as a provocation, an aversive event, or an aggression-related cue
➢ These variables influence the person’s present internal state including
cognitions, affects, and physiological arousal

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 Discuss doctor-patient relationship and interview techniques with
specialised populations

Introduction:

➢ The term “doctor–patient relationship” is a phrase used to describe the interpersonal

connection developed during patient interview
➢ It forms the foundations of medical ethics
➢ The doctor–patient relationship is important in the practice of healthcare and is
crucial for the delivery of high-quality health care for the diagnosis and treatment of
disease
➢ Doctors are expected to maintain a professional rapport with patients, uphold
patients' dignity, and respect their privacy
➢ Recently, the term “patient–doctor relationship” was suggested, to reinforce that the
treatment should always be patient centered
Importance:

1. The interview has three functions - gathering information, developing and maintaining a
therapeutic relationship, and communicating information. A patient who does not trust the
practitioner will not disclose complete information or a patient who is anxious will not
comprehend information clearly. The relationship therefore directly determines the quality
and completeness of information elicited and understood.

2. It is the major influence on practitioner and patient satisfaction. It contributes to practice

maintenance and prevention of practitioner burnout and turnover.

3. Patients encouraged asking questions and to participate in their care do better

biologically, in quality of life, and have higher satisfaction.

Components: cxxvii

1. First encounter- There is considerable apprehension about seeing a mental health

professional apart from the distress of mental illness. The misconceptions about psychiatric
treatment arising from stigma, misinformation, and misconceptions may add to the patient’s
anxiety. The patient’s experience of the first encounter sets the tone for subsequent
interviews or treatment that may follow in the future.

2. Comfort- Doctors should provide a reasonable level of comfort and assure the safety of
both the patient and the clinician.

3. Privacy and confidentiality are essential components of a good doctor patient

relationship. The level of confidentiality afforded the patient varies depending on the nature
of the illness of the patient. The doctor should consider telling the patient situations that may
lead one to share information without expressed consent. Examples include contacting
relatives of the patient to inform about imminent suicide or violence risk, transfer of
information in medical or psychiatric emergencies.

4. Rapport is the harmonious responsiveness of the physician and patient to one another
and is an essential component of a good doctor patient relationship.

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5. Empathy is the capacity to appreciate and understand the experience of the patient at an
emotional level. It is achieved when the doctor is able to imagine himself in the patient’s
position while maintains objectivity.

6. The demonstration by physicians that they understand what the patient is stating and
feeling. This understanding must be conveyed to the patient for a good therapeutic
relationship.

7. A good patient-doctor relationship is formed when there is recognition by the patient

that the physician cares. As the patient becomes aware that the physician cares, trust
increases and the therapeutic alliance becomes stronger. The doctor should provide
reassurance and put the patient at ease.

8. Informed consent- the patients has a choice in the provision of their care and should be
given the right to an informed consent before any kind of medical procedures.cxxviii

9. Shared decision making- is the concept wherein a patient gives informed consent to
treatment and he is given an opportunity to choose among the treatment options according
to their treatment goals, beliefs and wishes.

10. Transitional Care-Transitions of patients from one doctor to the other may decrease the
quality of care as it takes time to re-establish proper doctor–patient relationship. The doctor–
patient relationship is facilitated by continuity of care. Strategies of integrated care may be
required where multiple health care providers are involved, including horizontal integration -
linking similar levels of care, e.g. multiprofessional teams and vertical integration -linking
different levels of care, e.g. primary, secondary and tertiary care.cxxix

11. Closing the Interview- It is important to alert the patient to the remaining time. This
signal gives the patient the opportunity to plan how to use the time. Directly asking the
patient if there is anything else is a useful technique.

Interview Techniques With Specialised Populations

1.Patients with Psychosis

Patients with psychotic symptoms are frightened, guarded, and suspicious about the
purpose of the interview and the intentions of the doctor. Hallucinations may cause
inattention and distraction. These factors require adaptations to match the capacity and
tolerance of the patient. The psychiatrist should be alert for clues about the psychotic
processes during the interview. It is advisable to ask directly about any such behaviours or
comments. Patients may ask if the doctor believes the delusion. In this situation we should
not to endorse the false beliefs, but it is not helpful to challenge the delusion directly
particularly in the initial examination.

2. A Violent Patient

Safety for the patient, interviewer, and others present is of importance when engaging with
hostile or agitated patients. If one knows in advance, there is an opportunity to plan and be
ready with the supports. We should have an attendant during the interview to reduce risks in
these situations. It is good practice to alert the security, if present. Approach should be in a
calm, non-threatening and direct manner. Termination of some interviews must occur when

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the patient’s aggression escalates. Interviewing for violence risk includes - ideation to plan to
action, the nature and extent of the patient’s ideation, planning, and intent.

3. The Patient with Depression

They have difficulty participating in the interview due to psychomotor slowing, cognitive
deficits, and lack of motivation to engage caused by the depression itself. Feelings of
hopelessness may contribute to this. Their response to questions are latent and may lack
spontaneous explanation. The doctor may need to turn to more direct questioning. The
interview of severely depressed patients can be a tedious process and may require more
time to gather even minimally necessary information.

4. The Suicidal Patient

It is important to conduct suicide risk assessment in all psychiatric interviews. Suicide risk is
more in major depression, borderline personality disorder, high levels of anxiety, acute
psychosis, acute intoxication, patients who have become hopeless about their substance
use problems, acute grief and loss reactions, and patients with serious medical problems.
We must evaluate all risk factors and protective factors in suicidal patients.

5. The Deceiving Patient

Here the patients intentionally produce or exaggerate the symptoms. They are motivated by
secondary gain, like work excuses, disability, or to secure desired medications or primary
gains, like the psychological benefits of assuming a sick role.

The markers in interviews that raise suspicion include vague and contradictory responses,
symptom claims that are inconsistent with functional findings, claims that are far beyond the
variations of psychopathology. They may become irritated with attempts to clarify the nature
of complaints. The psychological tests designed to detect deceit are the Word Memory Test
and the Minnesota Multiphasic Personality Inventory [MMPI]). The doctor should try to
maintain an empathic approach to when discussing the issues and help the patient accept
responsibility.

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 Fregoli’s syndrome

Delusional misidentification syndromes(DMS):

➢ Delusional misidentification syndromes are characterised by the inability to register

the identity of something, whether it is an object, event, place or even a person
➢ They are of various forms - the syndrome of subjective doubles, intermetamorphosis,
Capgras syndrome and Fregoli syndrome
➢ However, all of these various syndromes have a common denominator: they are all
due to malfunctional familiarity processing during information processing
➢ Other commonalities among these syndromes are that they are discriminatory in
which object(s) are misidentified. Lastly, dopamine hyperactivity is evident in all
DMSs and thus, all syndromes utilize antipsychotic medications to help control DMS
➢ Capgras syndrome is the delusional belief that a friend, family member, etc., has
been replaced by a twin impostor
➢ Fregoli syndrome is the delusional belief that different people are in fact a single
person who is in disguise. It is also known as the delusion of doubles

Classification:
➢ It is classified under delusional disorders, unspecified type
➢ It is classed both as a monothematic delusion, since it only encompasses one
delusional topic, and as a delusional misidentification syndrome, a class of delusional
beliefs that involves misidentifying people, places, or objects
Epidemiology:

➢ The prevalence of Capgras syndrome was 1.3% (1.8% for females, 0.9% for males)
➢ Schizophrenia (50%) was the most common psychiatric diagnosis in these
patientscxxx

Clinical features:
➢ It can be seen in mental disorders such as schizophrenia, bipolar disorder and other
mood disorders
➢ It is often of a paranoid nature; with the delusional person feeling
themselves persecuted by the person they believe is in disguise
➢ A person with the Fregoli delusion can also inaccurately recall places, objects, and
events. This disorder can be explained by "associative nodes"
➢ The associative nodes serve as a biological link of information about other people
with a particular familiar face (to the patient)
➢ This means that for any face that is similar to a recognizable face to the patient, the
patient will recall that face as the person they know.cxxxi
➢ Fregoli syndrome is an illusion of positive doubles where there is an over-familiarity
with the environment
➢ This over-familiarity may have four causes:

1. Impaired self-monitoring-passive acceptance of inaccurate conclusions

2. Faulty filtering-tendency to select salient associations rather than a relevant

one

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 3. Mnemonic association from routine thoughts

4. Perseveration-unable to come up with an alternate hypothesis

➢ Coexistence of Capgras and Fregoli is a rare phenomenon

➢ Depersonalization and derealization symptoms are usually manifested in patients
exhibiting two misidentification delusionscxxxii

Etiopathogenesis:

1. Fusiform gyrus:

➢ MRI shows parahippocampal and hippocampal damage in the anterior fusiform

gyrus, the middle and inferior of the right temporal gyri
➢ The inferior and medial of the right temporal gyri are the storage locations for long-
term memory in retrieving information on visual recognition, specifically of faces;
thus, damage to these intricate connections could be one of the leading factors in
face misidentification disorders

2. Abnormal P300:

➢ Delusional misidentification syndrome is thought to occur due to dissociation

between identification and recognition processes
➢ The integration of information for further processing is referred to as working memory
➢ Fregoli’s is accompanied by abnormal working memory, specifically affecting the
prefrontal cortex
➢ The P300 (P stands for positive voltage potential and the 300 for the 300-millisecond
poststimulus) is an index of as working memory
➢ Patients generally exhibit attenuated amplitude and prolonged latencies of P300.
➢ These patients have trouble focusing their resources to a stimulus; this was
hypothesized to be caused by the neurodegeneration of the right hemisphere
➢ There is correlation between fregoli’s and gray-matter degeneration of the right
frontal region, which controls attentional resources
➢ This is important, because it can help determine the mechanisms, which can then
help determine a more effective target drug and/or treatment plan.cxxxiii

3. Levodopa treatment:

➢ Levodopa, also known as L-DOPA, is the precursor to several catecholamines,

specifically of dopamine, epinephrine and norepinephrine
➢ It is used to treat Parkinson's disease and dopamine-responsive dystonia
➢ The use of levodopa can lead to visual hallucinations and delusions
➢ In most patients, delusions were more salient than hallucinations
➢ With prolonged use of levodopa, the delusions occupy almost all of a patient's
attention. These delusions related to antiparkinsonian medications may be one of the
causes of Fregoli syndrome.cxxxiv

4. Traumatic brain injury:

➢ Injury to the right frontal and left temporo-parietal areas can cause Fregoli syndrome
➢ Overall, brain-injured patients were severely impaired in many executive functions
such as self-monitoring, mental flexibility, and social reasoning.cxxxv

330
Treatment:

a) It shows response to various biological treatment methods

b) In the setting of depression it responds to tricyclic antidepressants
c) In the setting of schizophrenia or organic psychosis it usually responds to
neuroleptics
d) In a schizophrenic setting it has more chances of responding to trifluoperazine either
given alone or in association with other medications
e) In certain cases combination of antipsychotic treatment with treatment of co-existing
organic dysfunction appears to be important.cxxxvi

331
 PSYCHOLOGY OF RAPE

Introduction:

➢ The recent surge in sexual violence towards women in India require a multi-
pronged response that should involve not just organised and non-organized
sectors, but also individuals as members of that society as perpetrators of rape
often have mental health and psychosocial risk factors that trigger, maintain and
perpetuate the offence
➢ Psychiatry can play a constructive and educative role in assisting criminal justice
agencies in managing this scourge.
Definition of rape:

➢ In law, rape is defined as vaginal or anal penetration in the absence of lawful

consent
➢ The source of penetration (e.g., penis, finger, or objects), object of penetration
(e.g., vagina, anal, or oral), gender of perpetrator, and victim and definition of
consent varies greatly across jurisdictions
➢ Rape is considered to have occurred when her consent has been obtained by:
(i) Putting her (or any person in whom she is interested, e.g., children, close
relatives) in fear of death or of hurt

(ii) The administration by him personally or through another of any stupefying or

unwholesome substance (so-called “Date-rape”)

(iii) When the age of the victim is below 16 years

➢ Moreover, Indian law (section 375 of Indian Penal Code) specifically states that if
a woman consents to sex, that consent is invalid and rape is still considered to
have taken place if the woman is suffering from “unsoundness of mind or
intoxication” so that she is unable to understand the nature and consequence of
that to which she gives consent
PSYCHIATRIC ASPECTS OF RAPE:

1. Neurobiological Impairments:

➢ Rape may be associated with organic brain damage and learning disability,
disorders associated with congenital or acquired brain damage.cxxxvii
➢ A critical developmental task for adolescent males involves learning to distinguish
between aggressive and sexual impulses, as this has consequences for their
ability to control aggressive tendencies during sexual experiences and activities
➢ They argue that both types of impulses - violent and sexual - originate from the
same brain structures.cxxxviii
➢ Sadistic rapists have shown abnormalities within the temporal horn
2. Psychiatric disorders:

332
 ➢ People with schizophrenia or related psychoses may often commit rape or show
abnormal sexual behaviour which is related either directly to the psychosis or
indirectly to disinhibition.cxxxix
➢ Patients with hypomania and mania become sexually disinhibited leading to such
offences.
THEORIES ABOUT PSYCHOLOGY OF RAPE:

Sexual offending literature consists of three main types of theories: Single-factor, multifactor,
and micro-theories.cxl

1. Single-factor theories:

➢ These refer to theories that attempt to explain a single unifying underlying cause of
sexual aggression, e.g., psychodynamic, evolutionary, cultural, or socio-cognitive
theories
➢ Single-factor theories cannot explain many of the rape cases, they do contribute in
generating good multifactor theories
1a. Psychodynamic theory:

➢ Freud believed that sexual aggression originated from a serious form of

psychopathology within the individual (or character disorder) that originated
from childhood and was extremely resistant to treatment. cxli
1b. Feminist theorists:

➢ This school of thought explain rape as a manifestation of male patriarchal

values and paternalism
➢ According to the social control theory of rape, rape and the fear it provokes
among women is one of a number of mechanisms used by men to subjugate
and control women.cxlii
1.c. Evolutionary theories:

➢ Some hypothesize that rape is the product of a direct adaptation that has
occurred in our ancestral past (e.g., male ancestors who raped were highly
successful, reproductively, as a direct outcome of forced copulation) while
others hypothesize that rape is the product of an indirect adaptation (e.g., it
was promiscuous sex that was directly selected for and forced copulation is a
by-product of this selection process). cxliii
➢ Other evolutionary perspectives, such as gene-culture co evolution theory
and niche construction theory may prove to be of greater use (i.e., clinical
fertility) as these have the capacity to incorporate genetic predispositions,
individual learning processes, and cultural resources into their explanations of
human mating behavior.cxliv
1.d. Social–cognitive theories of rape:

➢ This theory suggests that rapists hold any combination of five implicit
schemata:
1. Women as sexual objects (i.e., beliefs that women are sexually
preoccupied and receptive to sexual invitations)
2. Women are dangerous (i.e., women are malevolent, deceptive and highly
unpredictable)

333
 3. Entitlement (i.e., beliefs in male supremacy and control)
4. Uncontrollability (i.e., beliefs that strong sexual urges and impulses cannot
be controlled)cxlv

2. Multifactor theories:

➢ These combine a number of single factor theories into an explanation of interactions

and causal relationships to create an environment for rape to occur, e.g., confluence
model, integrated theory, quadripartite theory, and an unification of all these theories
into one metatheory - integrated theory of sexual offending
➢ These are useful in developing risk assessment and intervention strategies for
groups of offenders.cxlvi cxlvii cxlviii cxlix cl
2.a. Confluence model of sexual aggression:cli

➢ It hypothesises that when men feel that their sexual efforts are being thwarted via,
female rejection, or female promiscuity, then they are get angry, increasing the
likelihood that they will resort to coercion, and general domination over women in
order to increase their chances of reproductive success (the hostile masculinity
pathway)
➢ The proximate risk falls into six predictive categories:
(I) Rape tumescence

(ii) Hostile masculinity

(iii) Hostility directed at women

(iv) Offense supportive attitudes such as rape myth acceptance

(v) Antisocial personality characteristics

(vi) Sexual experience (utilized to measure opportunity to sexually aggress)

2.b. Integrated theory: clii

It focuses on the period of adolescence and concentrates on four types of factors i.e.,
biological, developmental, socio-cultural, and situational.

2.c. Quadripartite model of sexual aggression:cliii

It four core factors were implicated in rape:

➢ Physiological sexual arousal

➢ Cognitive distortions
➢ Affective dyscontrol
➢ Personality traits that arise from developmental experience
3. Microtheories:

➢ These are essentially descriptive theories developed from an analysis of the offence
data and offenders’ accounts of their behaviour

334
 ➢ They specify how offending occurs in terms of core cognitive, behavioral, affective,
volitional, and contextual factors and provide excellent shared relapse prevention
plans for offenders and their therapists/supervisors
4. Rehabilitation theories:

4.a. The relapse prevention model:cliv

➢ The main aim of treatment adopting this approach to heighten offenders'

awareness of abstinence threatening factors, and strengthen self-regulation
ability
4.b. The self-regulation model: clv

➢ It is the the processes (both internal and external) necessary for an individual
to implement actions required to achieve personal goals

335
 Psychophysiological measures of anxiety

Introduction:

➢ Psychophysiology is the branch of psychology that is concerned with the

physiological bases of psychological processes

➢ The psychophysiological markers that have been used to study dysfunctional neural,
serotonergic, cognitive and autonomic activities associated with anxiety disorders
include:

(1) Measures of autonomic nervous system

(1) Loudness Dependence Of The Auditory Evoked Potential

(2) Event-Related Potentials

(3) Heart Rate Variability (HRV)

(4) Genetic Polymorphisms

(5) Amygdala Hyperactivity And Dysfunctional Prefrontal Activity

(1) Measures of autonomic nervous system:

➢ Since anxiety leads to sympathetic over-activity it can be measured by the increase

in following: heart-rate, blood-pressure, palmar sweating (skin conductance),
salivation, pupil size, electromyogram, respiration, electroencephalogram

➢ These measures revert to normal values as soon as anxiety is alleviated. clvi

(2) Loudness of the auditory evoked potential:

➢ It measures activity in the primary auditory cortex in response to different tone

intensities and is a marker for the functioning of the central serotonergic system

➢ It is inversely proportional to central serotonergic activity

➢ It has been utilized to study dysfunctional serotonergic and dopaminergic activity in

patients with Generalised Anxiety Disorder.clvii clviii

(3) Event-Related Potentials:

1. P1:

➢ The first major positive voltage deflection occurring 50-165 ms after the onset of
stimulus—and the early posterior negativities (EPNs)—showing negative deflection
over the temporo-occipital sites within a time window between 150 (200) and 300
ms—in response to emotional stimuli

➢ High-trait anxiety patients show an enhanced early P1 component to fearful faces

relative to neutral faces at occipital electrode sites

336
 ➢ However, they do not show greater lateral parietal negativities (or EPNs) in response
to fearful faces, which may indicate attentional avoidance following the initial
attentional vigilance or the failure to differentiate threat from non-threat stimuli. clix clx

2. P2:

➢ The major positive voltage deflection occurring 50-165 ms after the onset of stimulus

➢ High-trait anxiety participants have greater amplitudes of the P2 component to angry

faces

➢ Greater P2 components indicate greater attentional allocation to threat-related

stimuli, which is frequently exhibited in individuals with anxiety disorders. iv

3. Error-related negativity (ERN):

➢ A negative deflection observed at fronto-central sites, is generated in the anterior

cingulate cortex around the time when an erroneous response is made and peaks at
50-100 ms after stimulus onset

➢ Larger ERN component has been associated with anxiety

➢ Administrating anxiolytics such as oxazepam and alprazolam has decreased ERN

amplitudes

➢ Error monitoring activity of the ACC indexed by the ERN may play a role as an
endophenotype of anxiety disorders.clxi clxii

(4) Heart rate variability:

➢ It refers to the differences in beat-to-beat alterations in heart rate and gives an idea
of the interplay between sympathetic and parasympathetic (vagal) activity in the heart

➢ Under resting conditions, the heart is predominately under the control of the
parasympathetic activity

➢ Reduced HRV indicates autonomic dysregulation associated with elevated

sympathetic activity and reduced vagal activity of the heart

➢ The intrinsic heart rate is approximately 105 beat per minute, resting heart rate is
only 60-80 beats per minute, suggesting that the heart is under the strong vagal
control

➢ Patients with anxiety disorders have reduced heart rate variability

➢ It is seen in panic disorder, Generalised Anxiety Disorder, and even children of

patients with panic disorder.clxiii clxiv

(5) Genetic predispositions seen in anxiety disorders are as follows:

1. The serotonin transport promoter polymorphism (5-HTTLPR):

➢ In human, serotonergic raphe neurons project to different brain structures (e.g.,

cortex, amygdala, hippocampus) and are integrates emotion, cognition, motor

337
 function, pain, circadian and neuroendocrine functions such as food intake, sleep and
sexual

➢ The serotonin transporter (5-HTT) plays a vital role in regulating serotonergic

neurotransmission by facilitating the reuptake of 5-HT from the synaptic cleft

➢ Polymorphism in the promoter region of the serotonin transporter gene, results in two
different alleles—the short (s) and long (l)

➢ Individuals carrying one or two copies of the s form had reduction in 5-HTT
availability and were associated with increased anxiety-related behaviours and
greater risk for developing anxiety in stressful life situations.clxv clxvi

2. Catechol-O-methyltransferase (COMT):

➢ COMT is an enzyme that plays an important role in the metabolism of brain

dopamine and norepinephrine

➢ The COMT gene can be found in chromosome 22q11 and contains several single
nucleotide polymorphisms (SNPs) that are functionally important

➢ For example, Val158Met (rs4680)—associated with encoding either valine (Val) or

methionine (Met)—plays an important role in modulating COMT activity in the
prefrontal cortex . Val158Met may be associated with anxiety disorders.clxvii clxviii clxix

3. Brain-derived neurotrophic factor (BDNF) gene:

➢ BDNF is a neurotrophin that plays an important role in neuronal growth,

differentiation, and synaptic plasticity

➢ BDNF plays a role in mediating effects of stress

➢ Reduced BDNF expression in the hippocampus was observed in response to stress,

which may contribute to hippocampus-dependent memory deficits and the decreases
in hippocampal volume associated with patients with post-traumatic stress disorder.
clxx clxxi

(6) Amygdala hyperactivity and reduced PFC function:

➢ Anxiety disorders are linked with hyperactivity of the amygdala

➢ People with anxiety have reduced activity in anterior cingulate cortex (ACC) and
lateral prefrontal cortex

➢ Functional magnetic resonance imaging (fMRI) studies revealed that effective

treatment caused reduced amygdala activity in patients with social phobia. clxxii clxxiii
clxxiv

338
The clinical uses of the measures are as follows:

1. Biofeedback- the process of gaining greater awareness of many physiological functions

primarily using instruments that provide information on the activity of those same systems,
with a goal of being able to manipulate them at will. It may be used as a form of treating
anxiety disorders.

2. Research- for the development of newer drugs and also finding out the etiological factors
in anxiety.

339
 Clinical assessment of personality

Definition:

Personality is defined as an individual’s enduring and pervasive motivations, emotions,

interpersonal styles, attitudes, and traits

Uses of personality tests:

1. Assisting in Differential Diagnosis-they assist in understanding the etiology of the

presenting psychiatric problem and help in deciding the prognosis of the disorder.

2. Providing Narrow-Band Assessment- clinicians need answers to specific questions, eg.

measuring the intensity of the state or trait anxiety, or the amount of a patient’s anger. These
are helpful in measuring severity and provide a baseline for future assessment.

3. Aiding in Psychotherapy- They are important for short-term, problem-centered therapy

where understanding the patient’s problem must be done quickly. Psychological assessment
are used in pretreatment planning, assessing progress of therapy and evaluating the
effectiveness of therapy.

PSYCHOLOGICAL TESTSclxxv

Objective Personality Tests

Patients are asked specific and standard questions in a structured written or oral format. The
patient’s answers are scored according to a fixed agreed-upon criterion. The data obtained
is compared to the data obtained from the normative group. The degree to which the patient
deviates from the norm is noted and is used in the interpretation and result formulation.

1. Minnesota Multiphasic Personality Inventory:

The MMPI-2 consists of 567 true/false questions and takes approximately 1 to 1½ hours to
complete. A minimum of eighth-grade education is required. The scales of the include the
validity scales, clinical scales, content scales, supplemental scales, and critical items.

Advantages-

• Large research base

• Most known and utilized objective personality assessment instrument

• Provides clinically useful information

Disadvantages-

• Required that the patient be able to read items, comprehend instructions, and follow
direction

340
 • some patients attempt to fabricate responses but validity scales are available

2. The Personality Inventory for DSM-5—Adult (PID-5):

It consists of 220 questions. It measures five domains :negative affect, detachment,

antagonism, disinhibition, and psychoticism. It also provides information on 1 of 25
personality trait facets including: anhedonia, anxiousness, attention seeking, callousness,
deceitfulness, depressivity,etc.

Advantages-

• directly tied to the DSM-5 model for personality disorders.

• a very easy scale for clinicians to administer

Disadvantages-

• available research is limited at the current time.

• rating reliability of a practicing clinician is not known

• the interrater reliability of practicing clinicians has not yet been established.

3. The Millon Clinical Multiaxial Inventory IV (MCMI-IV):

It consists of 195 true–false questions. It has 15 Personality Pattern Scales and five Validity
Scales.

Advantages

• easy to administer and takes only approximately 30 to 45 minutes to complete

• computerized interpretation and scoring service is available

Disadvantages

• it may overdiagnose psychopathology through many scale elevations

• it has a large number of scales with a limited number of items (195). Thus, the high
ratio of number of scales to number items presents methodological challenges of
scale reliability.

4. Personality Inventory-Revised (NEO-PI-R):

This is a personality assessment based on the Big Five Personality domains- openness to
experience, conscientiousness, extraversion, agreeableness, neuroticism. These five
personality domains are also known as the Five Factor Model (FFM). It contains 240 items
and takes approximately 30 to 45 minutes to complete.

Advantages-

Corresponds to the Five Factor Model for personality

Disadvantages-

341
The patient must be educated upto the sixth-grade level.

5. Personality Assessment Inventory:

➢ It consists of 344 items which require a fourth-grade reading level

➢ It takes about 45 to 50 minutes to complete

➢ It has 11 clinical scales

➢ These measure personality problems like somatic concerns, depression, paranoia,

borderline features, or alcohol or drug problems

➢ It also has five treatment-related scales that address problems like treatment
rejection, suicide ideation, or aggression

➢ Two PAI interpersonal scales measure dominance and warmth

Advantages

➢ The scales are nonoverlapping

➢ The reading level is low

➢ Four response choices to individual items are given.

Disadvantages-

➢ It does not have the strong research base found in the MMPI-2

6. 16 Personality Factor Questionnaire (16 PF)

It is a True–false; self-report format consisting of 16 personality dimensions.

Advantages

➢ It is a test with considerable research conducted on nonclinical populations

Disadvantages-

➢ Limited usefulness with clinical populations

.7. Rapid Personality Assessment Instruments:

➢ These measure some unidimensional aspect of personality

➢ The test is written in clear, simple language and provides face validity

➢ These can be completed in less than 15 minutes

➢ Some of them include: Eysenck Personality Questionnaire, State Trait Anxiety

Inventory, Michigan Alcoholism Screening Test (MAST-R) etc.

8. Other tests available are: California Personality Inventory, Psychological Screening

342
Inventory, Eysenck Personality Questionnaire etc.

Projective Measures of Personality

1. Rorschach test

It consists of 10 cards-some are coloured, and some are black-white.

Advantages-

➢ Most widely used

➢ Best researched

➢ A lot of interpretative data is available

Disadvantages-

➢ Some interpretations don’t have proven validity

2. Thematic Apperception Test (TAT)

It consists of 20 cards showing various ambiguous situations and the patient is asked to
construct a story around those cards with a beginning middle and ending. The Children's
Apperception Test, often abbreviated as CAT, is used in children aged three to 10 years.

Advantages

➢ Widely used method

➢ Provides valuable information about patients conflicts

Disadvantages

➢ Poor consistency in interpretation

➢ Time consuming administration

3. Holtzman Inkblot Technique(HIT)

➢ It consists of 2 parallel forms of inkblot cards with 45 cards per form

➢ Only one response is allowed per card, making research less troublesome

Advantages

➢ Easy to use and administer

Disadvantages

➢ Not widely accepted

➢ not directly comparable to Rorschach interpretive strategies

4. Sentence completion test

343
 ➢ Patient is asked to complete a set of sentences given to them it is available in various
languages.

Advantages-

➢ Brief administration time

➢ Can be a useful adjunct to clinical

Disadvantages-

➢ Easy falsification

5. Make-a-Picture Story (MAPS)

It is similar to TAT; however, it can be easily manipulated by the patient

344
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C.D. Kilts, J.E. Kelsey, B. Knight, T.D. Ely, F.D. Bowman, R. Gross, A. Gordon, A. Newport, , , D.J.
Nemeroff, C.B. Selvig, (2006). The neural correlates of social anxiety disorder and response to
pharmacotherapy. Neuropsychopharmacology, 0089-3133103122432253
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Sadock B. Kaplan and sadock's comprehensive textbook of psychiatry. 10th ed. Wolters Kluwer; 2017. p.
2595-2627.

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Psychotherapy

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 Behavioural measures used in CBT

Dr Abha Thakurdesai

Introduction:
➢ Cognitive behavioural therapy (CBT) is a psychotherapeutic modality devised by
Aaron Beck
➢ It is known to be highly effective in treating psychiatric disorders such as
depression and anxiety disorders
➢ It is based on the cognitive theory which states that in psychopathology, there are
faulty thoughts which come automatically to our mind (called automatic thoughts)
following certain situations which reinstate the psychopathology
o For instance, if a colleague does not acknowledge a depressed person,
he or she may feel it is because the colleague does not like him
o This thought will contribute to a depressed mood and the person may
start avoiding conversing with colleagues
o This behaviour may eventually result in the person feeling worse
➢ To deal with such maladaptive thoughts and behaviours, CBT utilises techniques
which can either be cognitive (dealing with automatic thoughts) or behavioural
(dealing with maladaptive behaviour)
➢ While both techniques go hand-in-hand, behavioural techniques are often used
first as a severely depressed patient may be unable to identify and work with their
automatic thoughts

• Daily activity schedule (DAS):

➢ Often the first thing done, is to ask a patient to complete a DAS

➢ The DAS helps chart out how the patient spend his or her day
➢ The DAS describes activities done or to be done on an hourly basis
➢ The DAS is then reviewed by the therapist
➢ Often a DAS helps pick up maladaptive behaviours
➢ It becomes easier to set behavioural goals with the patient as a part of therapy

• Mastery and pleasure:

➢ The DAS helps in the mastery and pleasure that an activity that they indulge in
gives them
➢ Both mastery (feeling of competence over a task) and pleasure (enjoyment
procured by doing an activity) are rated on a scale of 1-10 with 10 being the
highest amount of mastery or pleasure and 1 being the lowest amount
➢ This is an important task in planning behavioural activities
➢ Patients are often surprised to know that they enjoy more mastery than what they
had previously thought and enjoy certain activities more than what they had
previously thought

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• Graded tasks:
➢ In cases of moderate to severe depression, the patient may not be able to
complete a large task all by himself
➢ Thus, tasks are broken down and organised in an hierarchy depending upon
how small or large the task is and the overall difficulty level
➢ The patient is then asked to complete the smaller, easier tasks
➢ If he is able to, the patient realises that he can succeed
➢ This is then reinforced, and the patient is encouraged to move on to larger,
more complex tasks
➢ If the patient is not able to complete the task, the therapist evaluates for
interfering thoughts and evaluates them

• Cognitive rehearsal:
➢ As a part of this technique, the patient is asked to imagine and rehearse the
various steps in meeting and mastering an activity the patient perceives as
challenging
➢ This acts as a behavioural experiment, wherein the patient can actually
overcome interfering cognitive distortions and raises his self-confidence and
thus, the likelihood that the patient will actually do the task

• Self-reliance training:
➢ This technique is used in both outpatients and inpatients but is known to have
special significance in inpatients
➢ Patients are encouraged to become self-reliant by doing simple activities that
facilitate independence eg. making their own beds, doing their own shopping,
cooking their own meals

• Role-playing:
➢ Through this technique, patients can practise various psychological skills in the
safety on the therapist’s office
➢ For a socially anxious person, this may include initiating a conversation
➢ The interfering automatic thoughts are elicited are also discussed
➢ Thus this technique acts on cognitive distortions and behavioural issues also

• Diversion techniques:

➢ Diversion techniques are important in helping patients get through difficult

times These include physical activity, social contact, work, play and visual
imagery

• Imagery and thought stopping:

➢ This technique is effective in impulsive or obsessive behaviour
➢ The patient is trained to think of a visual imagery that would inhibit them from
acting on an impulse that is ego-alien, for example, they are trained to think of a
stop sign

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 ➢ Patients battling obesity are encouraged to see an image of themselves as thin
and muscular when they feel like overeating
➢ Hypnosis or autogenic training is used to train patients to be able to create such
imagery
➢ A technique called guided imagery is also used, wherein patients are encouraged
to have fantasies that can be interpreted as wish fulfilment or attempts to master
disturbing affects or impulses

Discuss basic principles and applications of behaviour therapy /

Behaviour therapy for phobias / Behaviour modification in Panic disorder

Dr Abha Thakurdesai

Behaviour therapy:

➢ Behaviour therapy is a term used for various psychotherapeutic interventions which

are used to manage psychiatric disorders which are based on principles of learning.
Principles of behaviour therapy:

Classical conditioning:

➢ Classical conditioning is based on Ivan Pavlov’s classical experiment with the bell
and the dog
➢ As per classical conditioning, if a certain stimulus (called unconditioned stimulus) that
is generally associated with a response is paired with another stimulus (not
associated with a response) repeatedly, then the second stimulus (called conditioned
stimulus) too provokes the same response as the first stimulus, even in the absence
of the the first stimulus
➢ In Pavlov’s experiment, the dog which would earlier salivate at the sight of food,
gradually began to salivate at the sound of the bell which had repeatedly been paired
with the food.
Instrumental conditioning:

➢ When some action performed by a learner is instrumental in bringing about change in

the environment, the action is more (or less) likely to occur again (depending on
whether the change was positive or not.) due to learning
➢ When the consequences are positive, and the original action is repeated, it is called
positive reinforcement, when a usually occurring negative consequence does not
occur, it is called negative reinforcement
➢ If a negative event occurs as a result of the learner’s behaviour which would not
otherwise occur, it is called punishment
➢ If a positive event that occurs usually, does not occur because of a learner’s
behaviour, it is called omission of reinforcement.

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 ➢ Another concept of instrumental learning often used in therapy is shaping, wherein, a
target (desirable) behaviour is broken down into parts, and patient is encouraged to
do a part of the behaviour at a time. When the patient does so, it is reinforced
➢ As each part of the target behaviour is introduced and reinforced, it can be said that
the desirable target behaviour is being shaped in the person

Cognitive learning:

• Latent learning:
➢ Latent learning implies that learning occurs, however, it is not manifested in
behaviour until later

• Insight learning:
➢ Sometimes, when a person is faced with a problem, no solution occurs. However,
the solution comes suddenly, unexpectedly
➢ This is called insight learning
➢ The famous example of Archimedes’s eureka moment can be considered an
example of insight learning

• Imitation:
➢ This is when we learn our behaviour by observing and then modelling our
behaviour on someone else
➢ In residency, we learn by observing out teachers and supervisors and often
model ourselves (even though it may not be consciously) on their behaviour

Applications of behaviour therapy:

These principles are applied in therapy to deal with various psychiatric disorders

1. Phobias:

Systematic desensitization:

➢ In systematic desensitization, relaxation training is undertaken initially

➢ This can be with the help of Jacobson’s progressive muscular relaxation or by
any other technique
➢ After this, an hierarchy is constructed of the anxiety provoking stimuli
➢ The patient is then exposed to the least anxiety provoking stimulus and asked
to use the relaxation technique
➢ Once the patient is able to relax, he is then exposed to the next least anxiety
provoking stimulus and asked to relax
➢ This is then continued till the patient is able to relax with all the items in the
hierarchy
➢ This is based on the principle of reciprocal inhibition or counterconditioning in
which a person overcomes maladaptive anxiety in a situation by approaching
the feared situation gradually, in a psychophysiological state that inhibits
anxiety

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Graded exposure:

➢ This is similar to systematic desensitization in terms of creating an hierarchy

➢ However, relaxation therapy is not taught or done at the time of exposure
➢ Patient is exposed to the anxiety provoking situations as per the hierarchy
(from least anxiety provoking to most anxiety provoking), and encouraged to
deal with the anxiety
➢ Gradually, due to habituation, the patients anxiety reduces

Flooding:

➢ In flooding, the patient is exposed to a very anxiety provoking situation all at

once and is not permitted to leave till his anxiety subsides
➢ This technique is often distressing to the patient and thus, not used often in
therapy

Panic disorder:

➢ Relaxation techniques like paced breathing, Jacobson’s progressive muscle

relaxation can be used to decrease the anxiety in those suffering from anxiety
disorders
➢ Behavioural principles are involved in these techniques
➢ In panic disorder, various safety behaviours are used by the patient, for
example, a person having a panic attack who believes that a catastrophe
such as fainting is imminent is likely to engage in behaviour designed to
prevent the catastrophe, such as sitting down or trying to relax
➢ Whilst the behaviour may relieve anxiety it unintentionally preserves the belief
in the catastrophe
➢ Under these conditions each panic becomes an example of a 'near-miss'
rather than a disconfirmation of belief, and danger may seem subsequently
more evident
➢ Thus, in panic disorder, behavioural experiments are created to simulate the
symptoms of panic disorder (eg. intensive physical activity) and the patient is
asked to not engage in safety behaviour
➢ Once the patient sees that the feared ‘catastrophe’ does not occur and that
the anxiety abates, it leads to a gradual reduction in the symptoms of the
disorder

Depression:

Behavioural activation:
➢ Behavioural activation uses principles of behaviour therapy
➢ It is used in patients of depression who are avoiding activities secondary to
the depression
➢ The pleasure obtained from environmental activities reinforces the activity
and helps deal with the avoidance that develops in depression

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Schizophrenia

Social skills training:

➢ Patients with schizophrenia have deficits in social skills-whether they are

receptive social skills like recognizing a person’s emotions or expressive
social skills like content, volume and rate of speech in a conversation
➢ They cause impairment in those with psychosis
➢ Social skills training is based on principles of learning (modelling, operant
conditioning) wherein patients’ social skills are worked upon to improve socio-
occupational functioning and quality of life

Token economy:
➢ Token economy is often used in residential or inpatient settings to maintain
good behaviour among the residents
➢ Desirable behaviours are declared to the residents an they are awarded a
token for indulging in good behaviour
➢ The token can then be exchanged for something desirable-a walk in the
garden or extra TV time, for example
➢ Thus, operant conditioning is used for behavioural improvement

Obsessive compulsive disorder:

Exposure and response prevention-

➢ Like in systematic desensitization, an hierarchy of the anxiety provoking

stimuli is made which are arranged in an ascending order
➢ The patient is exposed to the least anxiety provoking item on the hierarchy
and is asked to not indulge in his compulsion (including mental compulsions)
➢ He is asked to not do so till his anxiety levels are reduced again after which
the session is terminated
➢ This is done with other items in the hierarchy (in ascending order) in order to
achieve improvement in OCD

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 Types, roles and efficacy of family therapy

Dr Abha Thakurdesai

Introduction:
➢ Family therapy can be defined as any psychotherapeutic endeavour that focuses on
altering the interactions between the family members and seeks to improve the
functioning of the family as a whole, or that of its subsystems and/or that of the
individual members of the family
➢ There are several schools of family therapy
➢ What a therapist uses depends upon his or her training, the context of therapy and
the personality of the therapist

1.Psychodynamic-Experiential Model:
➢ This model places emphasis on individual maturation in the context of the family
system
➢ Therapist seeks to establish an intimate bond with each family member and sessions
alternate between therapist-member of family and those between members of the
family
➢ Clear communication and honestly admitted feelings are given importance
➢ Family members are encouraged to exchange seats, touch each other while
communicating and make eye contact
➢ Metaphors used, body language and parapraxes used are evaluated to reveal
unconscious aspects of relationships in the family
➢ Sculpting:
1. ‘Sculpting’ may also be used, in which family members are asked to draw a
representative table arranging each other in the table as per their viewpoint of
their relationships in the past or at present
2. These tables are ‘sculpted’ or modified to suggest new relationships
3. The therapist expresses his or her subjective opinion time and again creating
a feedback loop of self-observation and change

2. Bowen model or Family Systems:

➢ This was the contribution of Murray Bowen
➢ It differentiates a person from his family and focuses on a person’s ability to be his or
her true self in the face of familial or other social pressures
➢ It assesses problem families for:
1. Degree of enmeshment vs ability to differentiate
2. Analysis of emotional triangles in the problems for which help is sought
➢ Emotional triangles are a three-person system such that the closeness of 2 family
members as either love or conflict tends to exclude the third
➢ When the excluded third person moves towards one of the two or one of the two
close family members move towards the excluded third, there are emotional issues
which surface

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 ➢ The therapist stabilises the part of the triangle causing the symptoms and then works
with the most psychologically available family member to achieve personal
differentiation so that the problem does not recur

3.Structural model:
➢ This model is given by Salvador Minuchin
➢ This model has a well-defined idea of a healthy family system
➢ In this model, families are viewed as single, interrelated systems assessed in terms
of significant alliances and splits among family members, hierarchy of power, clear
boundaries between generations and tolerance towards each other
➢ As per this model, there are problems in maintaining this structure which is causing
problems within the family
➢ Dysfunctional families are thought to be marked by impaired boundaries,
inappropriate alignments, and power imbalances
➢ Therapy focuses on the here-and-now
➢ It includes individual and group therapy

4. General Systems Model:

➢ This model views a family as a system where every member has a role and where
the action of every member causes a reaction from other members
➢ Often one member is blamed for the family’s problems
➢ When that member improves, another family member becomes scapegoat
➢ The therapist works using this theoretical base

5. Strategic model:
➢ Jay Haley and Cloe Madanes are known to have worked extensively on this model
➢ Strategic therapy claims that difficulties in families arise due to distorted hierarchies
➢ Dysfunctional families are believed to communicate in problematic repetitive patterns
(vicious cycles) that kept them dysfunctional
➢ These patterns arise as intended solutions by the family to some symptom
➢ The intended solutions then became the problem because the family had either over
or under responded to the symptom through their interactions

6. Systemic (associated with Mara Selvini-Palazolli aka 'The Milan model'):

➢ Systemic therapists see the family as a self-regulating system which controls itself
according to rules formed over a period of time through a process of trial and error
➢ They are interested in the rule-maintaining characteristics of communication and
behaviours, and assume that the way to eliminate a symptom is to change the rules
➢ An interview consists almost entirely of questioning of the family by the therapist
➢ Questioning is a recursive and circular process, with each question building upon the
family's response to previous questions
➢ Emphasis is placed on exploring differences between family member's behaviours,
emotional responses and their beliefs at differing points in time

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7. Transgenerational model:

Transgenerational family therapy aims to understand how families, across generations,

develop patterns of behaving and responding to stress in ways that prevent health
development and lead to problems

8. Solution focused therapy:

Solution focused therapy emphasises solutions over problems
➢ In fact, it sees the problem as being maintained by a focus on the problem to the
exclusion of the solution behaviour which is already happening
➢ The therapist collaborates with the family through in-depth questioning to focus on
the solutions already being used by the clients
➢ This is underpinned by a belief that people have the capacity to develop their own
solutions, even if they are not using it
➢ Blame, shame and conflict are seen as issues which impede people from realising
these solutions
➢ The therapist is non-interventionist
➢ Silences are tolerated when they arise in order to see what happens next
➢ The presumption here is that the more the therapist intervenes, the more he or she
will impose their own understanding and interpretation onto the family
➢ The focus is on the present and the future
➢ How a problem has arisen is not important
➢ The emphasis the family places on the problem is accepted by the therapist as he or
she is not interested in changing the family's definition

Role and efficacy:

Family therapy is known to be effective in relationship problems in a marital or familial setup.

The following are a few situations where family therapy can be used:
• When problems exist across generational boundaries. For example, a grandparent
feeling excluded from access to grandchildren
• At important times of transition-leaving the family home, following the birth of a child.
• When a family requests for a family therapy approach.
• When a serious psychiatric or medical illness exists in a family member
• Families stressed due to cultural or religious differences
• When sibling issues are beyond the control of the parent-eg. one sibling bullying the
other
• In cases of family conflict due to societal pressures and prejudices eg. parents
struggling to accept child’d homosexuality
• If a family member is interfering with another’s individual therapy eg. intrusive parents
threatened by the independence of their adolescent child
• Issues that stem from recombined families eg. problems adjusting to a stepfather in
the family
• When a child or adolescent is perceived as a ‘problem’. Eg. an adolescent using
drugs

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 Procedure And Efficacy Of Computerized Cognitive Therapy

Dr Abha Thakurdesai

Introduction:

1. Cognitive therapy was put forth by American psychiatrist, Aaron Beck

2. It is based on the cognitive theory, which states that the emotions and bodily
changes we feel and the behaviours we indulge in, in response to an event are
determined by thoughts which come to our mind automatically after the event
3. Cognitive therapy aims to correct these maladaptive thoughts so that the ensuing
mood and bodily responses and behaviour improve, leading to an improvement in the
psychopathology which leads to an increased amount of these maladaptive thoughts
in the first place
4. Cognitive therapy or Cognitive Behavioural Therapy (CBT) has evolved into a
treatment modalities for several psychiatric disorders and psychological problems
and has a large evidence base supporting its use in the same
Shortcomings of cognitive therapy:

➢ However, conventional therapy has some obvious shortcomings

➢ Therapy requires multiple sessions
➢ Often, it is not possible for a person to be able to visit the therapist office due to other
priorities
➢ Sometimes, the therapist may be located far away from the patient, thus making
regular therapy implausible or impossible
➢ This is especially true in a country like ours wherein a patient in a small town or
village may not have access to therapy services due to geographical barriers
➢ Sometimes the stigma of visiting a mental health professional stops a patient in need
of help from undergoing therapy
➢ As CBT therapists are few, patients may have to wait a long term before they are
able to get access to therapy. Many find conventional therapy expensive
➢ In view of all these comings, models for computerized cognitive therapy or
computerized cognitive behavioural therapy (CCBT) were developed
Computerized cognitive therapy: Procedure

➢ Computerized cognitive behavioral therapy (CCBT) delivers CBT via an interactive

computer interface delivered by a personal computer, internet, or interactive voice
response system", instead of face-to-face with a human therapist using specific
software
➢ Therapist involvement is nil or minimal
➢ CCBT is different from online therapy in that online therapy uses the computer as a
means of delivery with the computer itself playing the role of a medium, whereas the
computer plays a more active role in computerized therapy
➢ In CCBT, encoded logic (algorithms) can automatically formulate an individualized
treatment plan for each user

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 ➢ CCBT has potential to improve access to evidence-based therapies, and to
overcome the prohibitive costs and lack of availability sometimes associated
conventional CBT
➢ It may be possible in the long run to develop phone-based apps with softwares that
can deliver CCBT to patients
➢ CBT is well suited for computerization, as the treatment strategy follows a well
defined and formal methodology
➢ However, forms of therapy that rely more heavily on verbal interaction and the
patient-therapist relationship are not yet possible

CCBT: Efficacy

➢ Computerized cognitive therapy has been studied in:

1. Depressive disorders (mild-moderate)
2. Anxiety disorders
3. Substance use disorders
4. Post-traumatic stress disorder

➢ CCBT has been found in meta-studies to be cost-effective and often cheaper than
usual care
➢ It is found to be effective for mild-moderate depression and anxiety disorders
➢ A review of CCBT in the treatment of OCD in children found this interface to hold
great potential for future treatment of OCD in youths and adolescent populations
➢ Most internet interventions for posttraumatic stress disorder use CCBT
➢ However, more studies are needed before we can draw a final conclusion about its
efficacy
➢ CCBT can also be used to treat mood disorders amongst non-heterosexual
populations, who may avoid face-to-face therapy from fear of stigma although so
specific such program has yet been developed
➢ Studies however show a low uptake and completion rates
➢ CCBT completion rates and treatment efficacy have been found in some studies to
be higher when use of CCBT is supported by a therapist

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 Psycho-Education In Psychiatric Illness

Dr Abha Thakurdesai

Introduction:

➢ Psychoeducation is an information based behavioural training aimed at adjusting

lifestyle to cope with a disease or disorder and to improve outcome
➢ The term has been coined by Anderson et al
➢ It consists of 4 elements- education about the illness, problem-solving training,
communication training and self-assertiveness training whereby relatives are also
included
➢ As per the American Psychiatric Association, it is an evidence based psychological
intervention in managing schizophrenia and bipolar disorder
➢ However, it has been used for years to manage chronic medical illnesses
Importance of psychoeducation:

In case of mental illnesses, family members are known to be stressed out

Family stress does not cause serious mental disorders but can be a precipitant of
relapse in individuals
Psychoeducation helps:
✓ Reduce admission rate
✓ Decrease duration of admission stay
✓ Improve compliance with treatment
✓ Create improvement in overall disease parameters
✓ Decrease morbidity
✓ Reduce distress
✓ Enhance coping
✓ Overcome stigma ridden view of illness
✓ Reduces helplessness in caregivers
✓ Enhance a proactive attitude in caregivers
Principles of psychoeducation

Some core principles of Psychoeducation that have been identified include:

1) an emphasis on a learning exchange among providers and recipients that

recognizes both professional and every day knowledge

(2) a sequenced curriculum that guides facilitators and offers illness-specific

information, general information related to stress and coping, and enough flexibility to
attend to the needs of a given individual or group

(3) time allotted for processing information and emotions that may be upsetting,
mysterious, or difficult to understand

(4) strategies to enhance functioning, quality of life and reduce stigma and burden
among participants

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 (5) careful attention to adjustment of content, timing, and approach based on cultural
context and language

Psychotherapeutic components of psychoeducation:

 The psychotherapeutic components in psychoeducation offers safety, structure,

feedback, and time for participants to absorb information that may be unfamiliar and
challenging and may trigger complex emotions

 Some factors that have been identified include:

1) Development of a good therapeutic relationship between the patient and the

doctor and/therapist

2) Empathetic responses to patients

3) Respectful attention to negatively held beliefs about illness

4) Stimulation of hope and reassurance of patients

5) Experience of a ‘shared fate’ idea among patients (when group psychoeducation

is done)

Elements of psychoeducation:

 Name of the disorder and diagnosis

 Prevalence, onset and course

 Characteristic Symptoms and related problems

 Theories about the etiology and factors affecting its course (i.e. Stress-vulnerability
model)

 Pharmacological Treatment: Names and types of medication, clinical effects, side

effects

 Psychosocial Treatment: Psychotherapy and Counselling, Family Psychoeducation,

Psychiatric Rehabilitation

 Family and other support in social system

 Self Help/Peer Support

Psychoeducation is often carried out over multiple sessions. It can be started soon after
evaluating the patient and starting him on a first line of management. It is often done in
groups. The optimal size of a group is 8-12 member. It can involve patients, caregivers or
both. It is important to remember that although it is an evidence-based intervention in
schizophrenia and bipolar disorder, it is never the only treatment used. It is used in addition
to pharmacotherapy.

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 Rational Emotive Behaviour Therapy

Dr Abha Thakurdesai

Rational Emotive Behaviour Therapy (REBT) is a school of psychotherapy developed by

Albert Ellis. REBT is closely linked to the school of cognitive therapy in that it emphasises
largely on the role of thoughts in psychopathology. However, the way of dealing with the
thoughts differs from conventional cognitive therapy.

The most basic premise of REBT is that almost all human emotions and behaviours are a
result of what people think, assume of believe. A good way of highlighting the role of
cognition in REBT is by the ABC model.

• A= Activating event and inference about what happened

For example, a friend passing the patient in the street and not acknowledging him. In such
the scenario, the patient may believe that the friend is ignoring him as he doesn’t like him

• B= Belief about A
In the example above, the patient may believe that he is unacceptable as a friend and thus,
worthless as a person.

• C=Reaction/Consequence
Emotions: depressed

Behaviours: avoiding people.

Most beliefs mentioned in B are automatic and thus, out of conscious awareness. However,
often these beliefs are irrational, in that they hinder a person from achieving his or her goal,
cause distress and often are a distortion of reality.

Humans think at 3 levels:

1) Inferences- Theses are everyday inferences about what is going on, wherein we
guess what is happening. Inferences aren’t given a lot of importance in therapy.

2) Evaluations- Evaluations happen when we evaluate facts. Evaluations may at times

be conscious, but may also be out of conscious awareness at times. Often these
evaluations can be dysfunctional.
o Demandingness- Refers to the way people hold unconditional should and
musts-believing certain things should or must happen. These demands can
be about the self, others or the world and they eventually lead to ego
disturbance.
o Awfulising- This refers to exaggerating the consequences of past, present or
future events, seeing them as the worst that could possibly happen.
o Discomfort intolerance-This is based on the idea that one cannot bear some
event or circumstance.

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 o People rating- This represents an overgeneralization whereby a person
evaluates a specific trait, behaviour or action and applies that evaluation to
their total person. For instance, I did a bad thing, thus, I am a bad person.

3) Core beliefs:
Underlying what we think in specific situations are what we call ‘core beliefs’ which
are underlying rules that guide how people react to events and circumstances of life
in general.
The theory of change in REBT states that core beliefs have to be worked upon for
improvement. So if a patient fears disapproval, rather than rather than telling himself that
disapproval isn’t going to happen, the patient accepts that it may happen, but deals with your
underlying core belief that he always needs approval and must not ever receive disapproval.

Techniques used in REBT:

Cognitive techniques:

Rational analysis-

Analysis of specific episodes of behaviour to teach the client how to uncover and dispute
irrational beliefs.

Double standard dispute-

If a patient is holding a ‘should’ or self-downing belief about themselves, they can be asked
whether they would globally rate another person like a best friend doing the same thing.

Catastrophe scale-

Ask the patient to draw a scale from 1 to 100 and ask client to rate what he is feeling on it.
Then ask the patient to plot the other situations o the scale-ranging from drinking a cup of
coffee to being robbed to being diagnosed with cancer.

Devil’s advocate-

Also known as reverse role playing, in this, the patient is asked to get the client to argue
against his own dysfunctional belief.

Reframing-

In this, patient is asked to take events into perspective by framing them as ‘disapppointing’,
‘concerning’ rather than ‘awful’ or ‘catastrophic’

Imagery techniques-

Time projection-

Ask the client to visualise the unwanted event occurring, then imagine going forward in time
by a week, a month, a year and so on and considering how they will feel about the event
then.

The blow-up technique-

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The patient is asked to imagine the worst case scenario, coupled with humour to provide a
vivid and memorable experience for the client. Laughing at fears will help get control of
them.

Behavioural techniques-

Exposure-

This involves the patient entering a feared situation that they would normally avoid. This
helps to test the validity of ones fears de-awfulises them and develops confidence in ones
ability to cope

Shame attacking-

The patient is asked to deliberately act in ways in which the patient feels he will receive
disapproval.

Paradoxical behaviour-

When a client wishes to change a dysfunctional tendency, they are encouraged to behave in
a way contradictory to the tendency.

Postponing gratification-

This is used to combat low frustration tolerance by deliberately delaying eating sweets,
delaying smoking etc.

Risk taking-

The pupose is to challenge beliefs that certain behaviours are too dangerous to risk.

Applications of REBT

• Depression
• Anxiety disorders
• Eating disorders
• Anger management
• Adjustment disorders
• Stress mananagement
• Relationship issues

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 Client centered therapy

Dr Amitkumar Chougule

Introduction:

➢ Developed by Carl Rogers in 1950s based on his humanistic theory

➢ The main concept of Client centered therapy is that the therapist establishes a
relationship with the patient and helps the patient to reach a stage of realization where
they can help themselves
➢ The therapy is non-directive and the therapist does not suggest the patient or does not
express what he wishes to be changed
➢ Rather the therapist mirrors what the patient expresses and this helps the patient to
realize themselves and later able to decide about further
➢ The patient reaches a stage where they can decide for themselves or to come in terms
with the reality or present circumstance
➢ The patient learns about the self rather than living in an irrational world
➢ Therapy focuses in present circumstances rather than the past
2. Three attitudinal requirements in an effective therapist include:

1. Empathy with the patient's emotions and perspective:

➢ The therapist senses accurately the feelings and personal meanings that the
client is experiencing and communicates this understanding to the client
➢ When functioning best, the therapist is so much inside the private world of the
client that he or she can clarify not only the meanings of which the client is
aware but even those just below the level of awareness
➢ The processes of reflection and clarification fosters the process of empathizing
2. Genuineness/Congruence:
➢ Therapist openly expresses the feelings to the patient that are flowing at that
moment
➢ He is transparent to the patient so that the patient does not hold back anything
➢ Thus, there will be congruence between what is the gut feeling, what is in the
awareness and what is told to the patient
➢ This is brought about by close matching of the therapist and the patient
3. Unconditional positive regard for the patient:
➢ Therapist experiences a positive, acceptant attitude toward whatever the client
is at that moment
➢ Therapist prizes the client in a total rather than a conditional way and this caring
relationship is non-possessive

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 COUNTERTRANSFERENCE

Dr Amitkumar Chougule

Introduction:

Concordant identification:

• While the patient is free-associating, the analyst allows himself to resonate with the
associations, making trial identifications, consciously and unconsciously, with the
patient’s experience
• Racker applied the term concordant identification to this process
• It involves feelings but also impulses, attitudes, and defenses which closely resemble
those of the patient
• Even though this process occurs primarily in the analyst’s unconscious, it is under his
conscious control such that he does not lose track of his own identity as separate from
the patient
• Freud meant a different kind of influence, one that mobilizes unconscious conflict in
the analyst so that analytic work is impaired by entanglements with the analyst’s
unconscious impulses and feelings
• Kernberg referred to Freud’s idea of countertransference and later elaborations of it as
the classical approach
• In this view, countertransference manifests itself primarily as an analogue of the
transference that appears in patients
Definition:

➢ It is the analyst’s transference to the patient’s personality, material, or transference

➢ The psychic mechanism involved is displacement or projection onto the patient of
features of persons who were important to the analyst in his own early psychological
development, the analyst then experiencing the corresponding feelings, impulses,
attitudes, and identifications associated with those persons
Categories of countertransference:

Annie Reich has contributed substantially to the classical approach. She described two
categories of countertransference:

1. Acute
2. Permanent

Acute type:

➢ The acute variety refers to a specific countertransference event that appears suddenly
in response to a specific aspect of a particular patient
➢ For example, the constellation of a female patient’s transference might bear unusual
resemblance to the analyst’s memory of his mother during his oedipal years

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 ➢ Perhaps the patient treats the analyst as a child had been encouraged by his mother
to feel that he could claim more of her favor than could his father, leading to some
fixation
➢ If the analyst’s current life also happened realistically to involve significant deprivations
of love, he would be even more vulnerable to stimulation by his patient’s transference
➢ According to Reich, the most common dynamic of acute countertransference consists
of the analyst’s `getting stuck` in the trial (concordant) identification with his patient
➢ He loses, in one area of his experience, the distinction between himself and the patient
because his own similar infantile yearnings, needs, or conflicts have been too intensely
aroused.
Permanent type

➢ Permanent countertransference is the problem of a more pervasive neurosis in the

analyst, one that is an intrinsic part of his character structure
➢ Countertransference on this basis is evoked with all patients and cannot be effectively
modified by self-analysis
➢ Formal analysis is necessary
➢ Insofar as it is characterologically rooted and requires genuine character development
in order to be free of it, this countertransference is permanent
➢ An example of permanent countertransference would be an analyst whose mother was
emotionally weak, given to multiple anxieties and self-depreciation
➢ As a child, he would have assumed the function of soothing her anxiety and bolstering
her self-esteem
➢ His countertransference would consist in his unconsciously viewing all patients, male
and female, as mother, seeking to comfort them and give them a feeling of self-
satisfaction
➢ Out of this activity he could derive a rewarding sense of pleasure and esteem for
himself
➢ His patients would probably feel better while in treatment, but fundamental work with
neurosis would be limited
➢ According to Reich, this type of countertransference can also be called an `acting out`
by the analyst of his neurotic, infantile needs or conflicts

Complementary identification

➢ An important departure from the classical approach to countertransference emerged

with the concept of complementary identification
➢ The idea originated with Helene Deutsch and was fully developed by Racker
➢ It forms a counterpoint to the idea of concordant identification and is best explained in
that context
➢ As stated before, the patient comes to experience his neurosis in the form of
transference; that is, he responds to the analyst as if he were one or another primary
figure in his developing years in relation to whom his neurosis is formed
➢ Accordingly, the analyst becomes the subject of feelings and attitudes of considerable
intensity

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 ➢ The analyst maintains his sense of his own identity, therefore his objectivity, and
according to the classical approach he does not respond in accordance with the
identity his patient assigns him
➢ He can therefore, work at the level of useful concordant identification with the patient
instead of responding directly to the patient’s stimulations and provocations
➢ However, the analyst as a whole human being with natural inclinations tends to
respond in predictable ways when subjected to various stimuli
➢ He tends naturally, therefore, to take on feeling and attitudes that complement the
transference
➢ This response is equivalent to identification with the person who was the original object
in the patient’s childhood neurosis
➢ For example, in working with a masochistic patient, the analyst might find himself
wanting to scold the patient for blatant social misbehaviors that jeopardize the patient’s
reputation
➢ In reflecting objectively on his response and correlating it with other information, the
analyst might realize that patient is, in fact, trying to provoke punishment from him
through behaving like a bad child; moreover, the analyst notes that his inner response
is reminiscent of the patient’s claims that his father subjected him to unwarranted
scoldings
➢ It appears that the analyst has responded with complementary identification with the
patient’s father

The analyst’s total response

➢ Heinman and Racker contributed to the trend of expanding the inclusiveness of the
term countertransference
➢ They abandoned the distinction between trial (concordant) or complementary
identifications as opposed to (classical) countertransference identifications
➢ All bases and forms of identification, then, they referred to as countertransference
➢ It was especially Heinmann who also promoted the view that countertransference,
whether or not it involves the analyst’s neurosis, is useful for gaining insights about the
patient
➢ Margaret Little expanded the concept of countertransference more likely than other
analysts did
➢ She proposed that we speak of `the analyst’s total response to his patient’s needs`
which includes all possible classes of response in the analyst – conscious or
unconscious, neurotic or realistic, identification
The detection of countertransference -

Some of the common ways in which counter transference makes its appearance may be worth
mentioning:

1. Inability to understand certain kinds of material which touch on the analyst`s own
personal problems

2. Repeatedly experiencing erotic or affectionate feelings toward a patient

3. A dream or a parapraxis

4. Anxiety, depression or aggressive feelings towards the patient

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 5. Trying to help or getting involved with the patient in extra-analytic ways, for example,
in making certain financial arrangements, or housing arrangements

6. Several nonspecific signs of countertransference include boredom, drowsiness,

inhibition, daydreaming, or simply failure of the analysis to progress

Correction of counter transference

Rules of thumb proposed by Menninger:

1. Be constantly alert to the existence of countertransference

2. Try to recognize those manifestations of a disturbing countertransference which enter

into one’s work generally

3. Analyze their meaning in the light of one’s own personal self-knowledge

4. When one has become aware of feelings of countertransference, especially if they are
persistent, try to think through the analytic situation again and identify those features
or acts or words of the patient, which triggered off this reaction

5. No analyst can see everything; each one’s vision is limited by his personality.
Members of a group are mutually self-corrective. Since we are all partially blind, the
best we can do is to support each other so that the vision of one may make up for the
myopia of the other, and vice versa

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 Defence mechanisms and their need in routine life/ Discuss
defence and coping mechanism in detail

Dr Amitkumar Chougule

Introduction:

Structure of the Psychic apparatus:

➢ From a structural viewpoint, Freud divided the psychic apparatus into three
groups of functions designated as id, ego, and superego
➢ The ego represents a coherent organization of functions, whose task is to avoid
unpleasure or pain by opposing or regulating the discharge of instinctual drives
to conform to demands of the external world.
FUNCTIONS OF THE EGO:

➢ The ego comprises a class of self-functions that shares in common the task of
mediating between instincts and the outside world
➢ Thus, the ego is a subsystem of the personality and is not synonymous with
the self, the personality, or character
➢ Defence mechanisms are the functions of the Ego.
➢ According to Freud defences were:
1. Psyche’s major devices for managing threatening instinctual motivations
and affects
2. Operated unconsciously
3. Characteristic of neurotic syndromes
4. Dynamically motivated and reversible
5. Functionally adaptive as well as pathological
➢ More systematic and comprehensive study of ego defences was formulated for
the first time by Anna Freud.
➢ In her classic monograph The Ego and the Mechanisms of Defense, she
maintained that everyone, whether normal or neurotic, uses a characteristic
repertoire of defense mechanisms, but to varying degrees
Definition of defense mechanism:

According to DSM-IV defense mechanisms are described as autonomic psychological

processes that protect individuals against internal and external threatening situations
and the individuals are generally unaware of them.

Genesis of Defense Mechanisms:

1. In the early stages of development, defences emerge as a result of difficulties

in the capacity of ego functions to mediate pressures of the id and the
requirements and strictures of outside reality
2. In the classic theory, at each phase of libidinal development, associated drive
components evoke characteristic ego defences

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 3. Thus, for example, introjection, denial, and projection are defense mechanisms
associated with oral-incorporative or oral-sadistic impulses; whereas reaction
formations, such as shame and disgust, usually develop in relation to anal
impulses and pleasures
4. Defense mechanisms from earlier phases of development persist side by side
with those of later periods
5. When defences associated with pregenital phases of development tend to
predominate in adult life over more mature mechanisms, such as sublimation
and repression, the personality retains an infantile cast.

George Valliants Classification of Defense Mechanisms:

Narcissistic-Psychotic Defenses

These defenses are usually found as part of a psychotic process but may also occur in young
children and adult dreams or fantasies. They share the common note of avoiding, negating,
or distorting reality.

Projection:

➢ Perceiving and reacting to unacceptable inner impulses and their derivatives as though
they were outside the self
➢ On a psychotic level, this takes the form of frank delusions about external reality,
usually persecutory, includes both perception of one’s own feelings in another, with
subsequent acting on the perception (psychotic paranoid delusions)
➢ Impulses may derive from id or superego (hallucinated recriminations)
Denial:

➢ Psychotic denial of external reality, unlike repression, affects perception of external

reality more than perception of internal reality
➢ Seeing, but refusing to acknowledge what one sees, or hearing, and negating what is
actually heard, are examples of denial and exemplify the close relationship of denial to
sensory experience
➢ Not all denial, however, is necessarily psychotic
➢ Like projection, denial may function in the service of more neurotic or even adaptive
objectives.
➢ Denial avoids becoming aware of some painful aspect of reality. At the psychotic level,
the denied reality may be replaced by a fantasy or delusion.
Distortion:

➢ Grossly reshaping the experience of external reality to suit inner needs, including
unrealistic megalomanic beliefs, hallucinations, wish-fulfilling delusions, and
employing sustained feelings of delusional grandiosity, superiority, or entitlement
Immature Defenses:

These mechanisms are fairly common in preadolescent years and in adult character
disorders

They are often mobilized by anxieties related to intimacy or its loss

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Although they are regarded as socially awkward and undesirable, they often moderate
with improvement in interpersonal relationships or with increased personal maturity

Acting out:

The direct expression of an unconscious wish or impulse in action to avoid being conscious
of the accompanying affect. The unconscious fantasy, involving objects, is lived out and
impulsively enacted in behavior, thus gratifying the impulse more than the prohibition
against it

On a chronic level, acting out involves giving in to impulses to avoid the tension that would
result from postponement of their expression

Hypochondriasis:

➢ Transformation of reproach toward others arising from bereavement, loneliness, or

unacceptable aggressive impulses, into self-reproach in the form of somatic
complaints of pain, illness, and so forth
➢ Real illness may also be overemphasized or exaggerated for its evasive and
regressive possibilities
➢ Thus, responsibility may be avoided, guilt may be circumvented, and instinctual
impulses may be warded off
Introjection:

➢ The introjection of a loved object involves the internalization of characteristics of

the object with the goal of ensuring closeness to and constant presence of the
object
➢ Anxiety consequent to separation or tension arising out of ambivalence toward the
object is thus diminished
➢ If the object is lost, introjection nullifies or negates the loss by taking on
characteristics of the object, thus in a sense internally preserving the object
➢ Introjection can also take place out of a sense of guilt in which the self-punishing
introject is attributable to the hostile-destructive component of an ambivalent tie to
an object
➢ Thus, the self-punitive qualities of the object are taken over and established within
one’s self as a symptom or character trait, which effectively represents both the
destruction and the preservation of the object. This is also called identification
with the victim.
Passive-aggressive behaviour:

Aggression toward an object expressed indirectly and ineffectively through passivity,

masochism, and turning against the self

Projection:

On a nonpsychotic level, projection involves attributing one’s own unacknowledged

feelings to others; it includes severe prejudice, rejection of intimacy through
suspiciousness, hypervigilance to external danger, and injustice collecting.

Regression:

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A return to a previous stage of development or functioning to avoid the anxieties or
hostilities involved in later stages

A return to earlier points of fixation embodying modes of behavior previously given up

This is often the result of a disruption of equilibrium at a later phase of development

This reflects a basic tendency to achieve instinctual gratification or to escape instinctual

tension by returning to earlier modes and levels of gratification when later and more
differentiated modes fail or involve intolerable conflict

Schizoid fantasy:

The tendency to use fantasy and to indulge in autistic retreat for the purpose of conflict
resolution and gratification

Somatization:

1. The defensive conversion of psychic derivatives into bodily symptoms;

tendency to react with somatic rather than psychic manifestations
2. Infantile somatic responses are replaced by thought and affect during
development (desomatization)
3. Regression to earlier somatic forms or response (resomatization) may result
from unresolved conflicts and may play an important role in
psychophysiological and psychosomatic reactions
Neurotic Defenses:

These are common in apparently normal and healthy individuals as well as in

neurotic disorders. They function usually in the alleviation of distressing affects and
may be expressed in neurotic forms of behaviour

Depending on circumstances, they can also have an adaptive or socially

acceptable aspect.

Controlling:

The excessive attempt to manage or regulate events or objects in the environment

in the interest of minimizing anxiety and solving internal conflicts.

Displacement:

Involves a purposeful, unconscious shifting of impulses and/or affective investment

from one object to another in the interest of solving a conflict

Although the object is changed, the instinctual nature of the impulse and its aim
remain unchanged

Dissociation:

A temporary but drastic modification of character or sense of personal identity to

avoid emotional distress; it includes fugue states and hysterical conversion
reactions

Externalization:

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A general term, correlative to internalization, referring to the tendency to perceive
in the external world and in external objects components of one’s own personality,
including instinctual impulses, conflicts, moods, attitudes, and styles of thinking

It is a more general term than projection, which is defined by its derivation from and
correlation with specific introjects.

Inhibition:

The unconsciously determined limitation or renunciation of specific ego functions,

singly or in combination, to avoid anxiety arising out of conflict with instinctual
impulses, superego, or environmental forces or figures.

Intellectualization:

➢ The control of affects and impulses by way of thinking about them instead
of experiencing them
➢ It is a systematic excess of thinking, deprived of its affect, to defend against
anxiety caused by unacceptable impulses
Isolation:

The intrapsychic splitting or separation of affect from content resulting in repression

of either idea or affect or the displacement of affect to a different or substitute
content

Rationalization:

A justification of attitudes, beliefs, or behavior that might otherwise be

unacceptable by an incorrect application of justifying reasons or the invention of a
convincing fallacy

Reaction formation:

➢ The management of unacceptable impulses by permitting expression of the

impulse in antithetical form
➢ This is equivalently an expression of the impulse in the negative
➢ Where instinctual conflict is persistent, reaction formation can become a
character trait on a permanent basis, usually as an aspect of obsessional
character
Repression:

➢ Consists of the expelling and withholding from conscious awareness of an

idea or feeling
➢ It may operate either by excluding from awareness what was once
experienced on a conscious level (secondary repression), or it may curb
ideas and feelings before they have reached consciousness (primary
repression)
➢ The “forgetting” associated with repression is unique in that it is often
accompanied by highly symbolic behavior, which suggests that the
repressed is not really forgotten
Sexualization:

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The endowing of an object or function with sexual significance that it did not
previously have, or possesses to a lesser degree, to ward off anxieties connected
with prohibited impulses

Mature Defenses:

➢ These mechanisms are healthy and adaptive throughout the life cycle
➢ They are socially adaptive and useful in the integration of personal needs
and motives, social demands, and interpersonal relations.
➢ They can underlie seemingly admirable and virtuous patterns of behavior.

Altruism:

➢ The vicarious but constructive and instinctually gratifying service to others,

even to the detriment of the self.
Anticipation:

➢ The realistic anticipation of or planning for future inner discomfort

➢ Implies overly concerned planning, worrying, and anticipation of dire and
dreadful possible outcomes.
Asceticism:

➢ The elimination of directly pleasurable affects attributable to an experience

➢ The moral element is implicit in setting values on specific pleasures
➢ Asceticism is directed against all “base” pleasures perceived consciously,
and gratification is derived from the renunciation.
Humor:

The overt expression of feelings without personal discomfort or immobilization and

without unpleasant effect on others

Humor allows one to bear, and yet focus on, what is too terrible to be borne, in
contrast to wit, which always involves distraction or displacement away from the
affective issue.

Sublimation:

➢ The gratification of an impulse whose goal is retained, but whose aim or

object is changed from a socially objectionable one to a socially valued one.
➢ Libidinal sublimation involves a desexualization of drive impulses and the
placing of a value judgment that substitutes what is valued by the superego
or society.
➢ Sublimation of aggressive impulses takes place through pleasurable
games and sports
➢ Unlike neurotic defenses, sublimation allows instincts to be channelled
rather than to be dammed up or diverted
➢ Thus, in sublimation, feelings are acknowledged, modified, and directed
toward a relatively significant person or goal so that modest instinctual
satisfaction results.
Suppression:

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 ➢ The conscious or semiconscious decision to postpone attention to a
conscious impulse or conflict.

Narcissistic Immature Neurotic Mature

Denial Acting out Displacement Altruism

Projection Regression Dissociation Humor

Distortion Passive-aggressive Reaction formation Sublimation

behavior

Splitting Schizoid fantasy Repression Anticipation

Somatization Isolation Suppression

Introjection Rationalization Asceticism

Hypochondriasis Sexualization

Blocking Intellectualization

Reference:

WILLIAM W. MEISSNER, S.J., M.D. Classical Psychoanalysis. In Benjamin James Sadock,

Virginia Alcott Sadock, Pedro Ruiz, Editor. Comprehensive textbook of Psychiatry. 10th ed.
Wolters Kluwer;2017. P. 2219-28

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 Existential Therapy

Dr Amitkumar Chougule

History:
➢ The philosophers who have most influenced existential psychotherapy were the 19th
century philosophers of existence Kierkegaard and Nietzsche and the methods they
used were modeled on the phenomenological work of Husserl and Heidegger
➢ Modern philosophers who contributed are Sartre in 20th century
Four Worlds:
➢ There is no existential personality theory which divides humanity into types or reduces
people to part components
➢ Instead there is a description of the different levels of experience and existence with
which people are inevitably confronted
➢ The way in which a person is in the world at a particular stage can be charted on this
general map of human existence
Physical dimension:
➢ On the physical dimension (Umwelt) we relate to our environment and to the givens of
the natural world around us
➢ This includes our attitude to the body we have, to the concrete surroundings we find
ourselves in, to the climate and the weather, to objects and material possessions, to
the bodies of other people, our own bodily needs, to health and illness and to our own
mortality
➢ While people generally aim for security on this dimension (through health and wealth),
much of life brings a gradual disillusionment and realization that such security can only
be temporary
➢ Recognizing limitations can bring great release of tension
Social dimension:
➢ On the social dimension (Mitwelt) we relate to others as we interact with the public
world around us
➢ This dimension includes our response to the culture we live in, as well as to the class
and race we belong to (and also those we do not belong to)
➢ Attitudes here range from love to hate and from co-operation to competition
➢ The dynamic contradictions can be understood in terms of acceptance versus rejection
or belonging versus isolation
➢ Some people prefer to withdraw from the world of others as much as possible
➢ Others blindly chase public acceptance by going along with the rules and fashions of
the moment
➢ Otherwise they try to rise above these by becoming trendsetters themselves
➢ By acquiring fame or other forms of power, we can attain dominance over others
temporarily
➢ Sooner or later we are, however, all confronted with both failure and aloneness

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Psychological dimension:
➢ On the psychological dimension (Eigenwelt) we relate to ourselves and in this way
create a personal world
➢ This dimension includes views about our character, our past experience and our future
possibilities
➢ Contradictions here are often experienced in terms of personal strengths and
weaknesses
➢ People search for a sense of identity, a feeling of being substantial and having a self
➢ But inevitably many events will confront us with evidence to the contrary and plunge
us into a state of confusion or disintegration
➢ Activity and passivity are an important polarity here
➢ Self-affirmation and resolution go with the former and surrender and yielding with the
latter
➢ Facing the final dissolution of self that comes with personal loss and the facing of death
might bring anxiety and confusion to many who have not yet given up their sense of
self-importance
Spiritual dimension:
➢ On the spiritual dimension (überwelt) we relate to the unknown and thus create a sense
of an ideal world, an ideology and a philosophical outlook
➢ It is here that we find meaning by putting all the pieces of the puzzle together for
ourselves
➢ For some people this is done by adhering to a religion or other prescriptive world view,
for others it is about discovering or attributing meaning in a more secular or personal
way
➢ The contradictions that have to be faced on this dimension are often related to the
tension between purpose and absurdity, hope and despair
➢ People create their values in search of something that matters enough to live or die
for, something that may even have ultimate and universal validity
➢ Usually the aim is the conquest of a soul, or something that will substantially surpass
mortality (as for instance in having contributed something valuable to humankind)
➢ Facing the void and the possibility of nothingness are the indispensable counterparts
of this quest for the eternal
Psychological Dysfunction:
➢ There is no such thing as psychological dysfunction or being ill in the existential view
➢ Every way of being is merely an expression of how one chooses to live one's life
➢ However, one may feel unable to come to terms with the anxiety of being alone in the
world
➢ If so an existential psychotherapist can assist one in accepting these feelings rather
than trying to change them as if there is something wrong
➢ Everyone has the freedom to choose how they are going to be in life, however this
may go unexercised because making changes is difficult; it may appear easier and
safer not to make decisions that you will be responsible for

Therapeutic process:
➢ The existentially-oriented psychotherapist guides his or her clients to confront life's
anxieties
➢ If the client has not been fully exercising the freedom to choose, the counselor will lead
a discovering into how and why he or she is stuck

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 ➢ The client may have been allowing others to make important decisions which he or she
alone should be making, or the client may be afraid to take the risks required to grow
and is instead choosing an easy and non-threatening path
➢ The psychotherapist will encourage his or her clients to reflect on the aloneness and
meaninglessness of life, and to understand they must find their own ways to cope with
these anxieties
➢ The counselor does not try to eliminate these anxieties, but instead encourages the
client to face them head-on
➢ Alternative paths can be explored together
➢ The risks entailed with these paths can be evaluated, and the client will then be able
to make new, more authentic choices
➢ The existential psychotherapist is not overly concerned with the client's past; instead,
the emphasis is on the choices to be made in the present and future
➢ The counselor and the client may reflect upon how the client has answered life's
questions in the past, but attention ultimately shifts to searching for a new and
increased awareness in the present and enabling a new freedom and responsibility to
act
➢ The patient can then accept they are not special, and that their existence is simply
coincidental, without destiny or fate
➢ By accepting this, they can overcome their anxieties, and instead view life as moments,
in which they are fundamentally free

Existential psychology and influences over other therapies:

➢ One of the major offshoots of Existentialism as a philosophy is existential psychology
➢ Sometimes termed the Third Force Psychology, this branch of psychology was initiated
by Rollo May and Carl Ransom Rogers, both of whom were influenced by Kierkegaard
➢ With complete freedom to decide and being responsible for the outcome of said
decisions comes anxiety--or angst--about the choices made
➢ Anxiety's importance in existentialism makes it a popular topic in psychotherapy
➢ Therapists often use existential philosophy to explain the patient's anxiety
➢ Psychotherapists using an existential approach believe that the patient can harness
his or her anxiety and use it constructively
➢ Instead of suppressing anxiety, patients are advised to use it as grounds for change
➢ By embracing anxiety as inevitable, a person can use it to achieve his or her full
potential in life
➢ Humanistic psychology also had major impetus from existential psychology
➢ Logotherapy asserts that all human beings have a will to find meaning, and that
serious behavioral problems develop when they cannot find it
➢ The therapy helps patients handle the responsibility of choices and the pain of
unavoidable suffering by helping them decide to give life meaning

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 Gestalt therapy

Dr Amitkumar Chougule

Introduction:
➢ An existential and experimental psychotherapy, started by Fritz perls, Laura perls and
Paul Goodman in 1950s in USA
➢ The word Gestalt means whole – it has derived from the teachings of Goldstein who
said self-actualization needs self-transcendence, that is a person has to realize that he
is part of a whole
➢ Gestalt therapy derives its components from humanistic theories, eastern philosophy
and socio-political ideas prevalent during that time
Principle:
➢ The main principles of Gestalt therapy are “I and thou here and now”
➢ It concentrates on the here and now problems and emphasizes relationship between
the therapist and client
➢ Here the client is not interpreted but encouraged to discover which is a major change
compared to psychoanalysis
➢ Therapy focuses on process rather than content
➢ It is a method of awareness, by which perceiving, feeling, and acting are understood
to be separate from interpreting, explaining and judging using old attitudes
Process:
The important components of Gestalt therapy are:
1. Phenomenological method
2. Dialogical relationship
3. Field – theoretical strategies
4. Experimental freedom

1. Phenomenological method:
Consists of 3 principles, namely
a. Rule of epoche: one sets aside all prejudice and biases in order to prevent
expectations
b. Rule of description – description and not interpretation
c. Rule of horizontalization – all phenomenon are important equally
The gestalt therapist when explaining the phenomenon focuses on these aspects for time
being and later uses interpretation

2. Dialogical relationship:
➢ Here the therapist and client both enter in to the process
➢ Therapist doesn’t assume a false role and doesn’t try to control the situation; rather he
surrenders to what takes place between them
➢ The client is encouraged to present as he chooses, a process known as inclusion
➢ This includes even the resistances, and these are not considered as gimmicks but
assumed as this is how the client is

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3. Field – theoretical strategies:
➢ This includes both ontological (physical) and phenomenological (all subjective
experiences) fields
➢ Gestalt therapist chose to work with these field dynamics which makes them what they
do strategic
4. Experimental freedom:
➢ As the whole therapy is experimental, the client is encouraged to experiment and
discover
➢ Through experiments, the therapist supports the client’s direct experience of
something new instead of the mere talking about the possibility of something new
➢ An experiment can also be conceived of as a teaching method that creates an
experience in which a client might learn something as part of their growth

Differences from other school – mainly psychoanalysis

1. Here and now therapy. Doesn’t give much importance to past
2. Derives some of its concepts from humanistic perspectives
3. Emphasizes for scope of client to improve
4. Experimental and discovery rather than interpretation; both client and therapist
learns and there is scope for experiment and not mere talking
5. In contrast to the psychoanalytic stance in which the "patient" introjects the
attitudes/interpretations of the analyst, in Gestalt Therapy the client must "taste"
his/her experience, and either accept or reject, but not introject, or "swallow whole"
6. Hence, the emphasis is on avoiding interpretation and encouraging discovery
7. This is the key point in the divergance of GT from traditional psychoanalysis —
growth occurs through gradual assimilation of experience in a natural way, rather
than by accepting the interpretations of the analyst; thus, the therapist should not
interpret, but lead the client to discover for him or herself

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 Interpersonal therapy

Dr Amitkumar Chougule

Developed by Klerman, Weissman in 1970s

Theory
• Based on interpersonal theory given by Adolf Meyer, Harry stack Sullivan, John Bowlby
• Life events occurring after formative years influence psychopathology
• Uses life events in non etiological fashion
• Connection between current life events and mood disorder to help patient understand
and deal with his episode of illness
Model
• Depression is a medical illness and not patient’s fault
• Uses diagnostic manuals and rating scales
• Gives depressed patients sick role, exempting them from what their illness prevents
from doing
Strategy
• By solving interpersonal problem, patient will both improve his life situation and
simultaneously relieve the symptoms of depressive episode
• Interpersonal problems are of four types
1. Grief – complicated bereavement
2. Role transition
3. Role dispute
4. Interpersonal deficits
Phases
First phase
1. Diagnostic evaluation using standard criteria
2. Provide sick role
3. Interpersonal inventory – review patient’s current social functioning and close
relationships
4. Identify changes in relationships proximal to onset of symptoms- define focus of
treatment
5. Assess need for medication and patient preference
6. Link depressive symptoms to patient’s interpersonal situation – formulation of care
using one of 4 interpersonal problem areas

Second phase
Pursue strategies specific to chosen interpersonal problem area
1. Grief –
a. Facilitate catharsis of mourning
b. Find new activities or relationships to compensate for the loss
2. Role disputes
a. Conflicts with significant others

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 b. Explore the relationship – nature of the dispute, whether it has reached
deadlock or not, available options for its resolution
c. If these efforts fail, conclude that relationship has reached dead lock and end
relationship
3. Role transition
a. Change in life status
b. Mourn for the loss of old role
c. Recognize positive and negative aspects of new role
d. Attempt to gain mastery over new role
4. Interpersonal deficits
a. Patient lacks social skills in initiating and sustaining new relationships
b. Help patient to develop new relationship and skills
Final phase
1. Support patient’s newly regained sense of independence and competence
2. Recognize and consolidate therapeutic gains
3. Help to anticipate depressive symptoms in future
4. Develop ways of identifying and countering depressive symptoms should they arise in
future
5. Deemphasize termination – instead graduation from treatment
If patient is not improved it is the failure of treatment, neither patient nor the therapist have
failed and consider alternative treatment

IPT techniques:
1. Here and now problems
2. Therapist takes an active, non-neutral, supportive role and hopeful stance to counter
patient’s pessimism
3. Emphasize options available which patient has not seen
4. Stress to try out and test these options
5. Help to link out the life events to mood symptoms
These are facilitated by:
1. Opening question
2. Communication analysis – recreation of recent and affectively charged life
circumstances
3. Exploration of patient’s wishes and options
4. Decision analysis – which options to employ
5. Role playing – rehearse tactics for real life

Difference between IPT and psychodynamics

1. Focus on real life change
2. Medical model
3. Here and now rather than childhood or developmental issues
4. Avoidance of transference and dream interpretation
5. Not addressing enduring aspects of personality
IPT Vs CBT
1. Less structured
2. No home works
3. Different feel
4. Focus on interpersonal issues

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Similarities between IPT and CBT
1. Here and now
2. Role playing
3. Focus on syndromal constellation

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 Interpersonal social rhythm therapy

Dr Amitkumar Chougule
Background:
➢ Psycho-chrono biological theory of affective illness states that circadian rhythms and
sleep wake cycles have significant reciprocal relationship with mood
➢ Social cues that entrain these cycles may act as triggers for mood episodes
➢ Social cues are of 2 kinds;
o Zeitgebers: Persons, social demands or tasks that set the biological clock
o Zeitstorers: Physical, chemical or psychosocial events that disturb the
biological clock
➢ In studies it has been observed that stressful life events were associated with onset of
both manic and depressive episodes and life events (regardless of the severity of
threat) associated with the social disruption were associated with onset of manic
episodes
➢ So IPSRT tries to normalize the social rhythm and at the same time focus on patient’s
interpersonal milieu and current mood status
➢ Therapist also attends to the role of these interpersonal problems in disrupting the
social rhythm regularity

Treatment description:
IPSRT is a manual based therapy focusing on:
1. Link between mood and life events
2. Importance of maintaining daily rhythms
3. Identification and management of precipitants of rhythm dysregulation mainly
interpersonal triggers
4. Facilitation of mourning to the lost healthy self
5. Identification and management of affective symptoms
Phases of therapy:
1. Initial phase:
Treatment may be initiated while the patient is fully symptomatic, subsyndromal, or
euthymic
Duration of the initial phase may vary from several weeks to several months,
depending on the severity of the patient’s current symptoms.
Steps of initial phase are:
1. Obtaining a history of the illness – focus on events leading to current and
previous episodes
2. Conduct an interpersonal inventory - consists of a review of all important
past and present relationships as they relate to the current episode. The

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 therapist asks about the patient’s life circumstances and requests a description
of the important people in his or her life. In addition to outlining the “cast of
characters” in the patient’s life, the therapist probes the quality of those
relationships, asking the patient to describe satisfying and unsatisfying aspects
of relationships, unmet expectations of others, and aspects of relationships that
the patient would like to change.
3. Identify an interpersonal problem area –
➢ The therapist listens for perturbations in relationships that may
correspond temporally to the onset or maintenance of mood symptoms
➢ Understanding the relationship between interpersonal difficulties and
the onset of affective symptoms will help the therapist identify an
appropriate treatment focus for the intermediate phase of treatment
4. Educate the patient about the disorder:
➢ Information about bipolar symptoms, prescribed medications,
medication side effects, and so forth
➢ The therapist also begins to help the patient understand the possible
role of social and circadian rhythm disruption in precipitating his or her
episode
5. Initiate the Social rhythm metric:
➢ 17 item self report form which requires patients to record daily activities,
whether each occurred alone or with others present, and how
stimulating (i.e., quiet vs. interactive) these others were
➢ The patient also rates his or her mood each day
➢ In the initial phase of IPSRT, however, no effort is made to regulate
these daily rhythms

Intermediate phase:
a. Social Rhythm Strategies
b. Interpersonal Strategies

a. Social Rhythm Strategies:

• A behavioral approach to help the patient alter those activities that promote rhythm
irregularities
• Determine whether the patient’s social rhythm instability results from
untreated/prodromal bipolar symptoms or from a self-imposed lifestyle choice
• If it is due to symptoms of illness adjust the medications and if due to lifestyle choices
then explain that disruptions prevent from complete recovery
• Discuss general strategies to maintain social rhythm and identify SRM goals – short
term and long term
• IPSRT then encourages the patient to make relatively significant life changes in order
to protect the integrity of his or her circadian rhythms and sleep–wake cycle
• A very regular lifestyle can seem “boring” and unappealing a healthy balance between
stability and spontaneity need to be achieved
• Pursue this aspect of treatment over many months because seasonal variation in mood
and energy often occurs in bipolar patients. Ex: busier schedule during the winter

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 months when pts would typically tend toward depression but must learn to curtail these
same activities during the summer months when they are at increased risk for a mania.
• If changes cannot be avoided, adapt to the changes in routine by gradually entraining
the rhythms to a new schedule

b. Interpersonal Strategies:
Similar to standard IPT but in addition therapist also attends to the role of these interpersonal
problems in disrupting the social rhythm regularity
4 major areas are noticed:
1. Grief – allow the pt to mourn for the loss of healthy self
2. Interpersonal role disputes – bipolar pts are more prone for frequent role disputes
and the relationship is reciprocal
3. Role transitions – Major life changes are also more frequent among pts with bipolar
disorder
4. Interpersonal deficits – disease associated symptoms may result in multiple failed
relationships, recurrent patterns of conflict with other workers and disrupt social rhythm
regularity

3. Preventive phase:
• IPSRT is designed, above all, to prevent future mood episodes and enhance
functioning during relatively euthymic periods, the preventative phase is a crucial
component of this treatment
• Treatment frequency decreases to monthly and lasts 2 or more years
• Therapist continues to encourage the patient to maintain regular social rhythms and
addresses problems as they arise
• The patient works on his or her interpersonal problem area(s), although the specific
interpersonal focus may differ from that of the acute phase

4. Termination:
• Termination is handled gradually, occurring over four to six monthly sessions
• Patients are reminded about available resources for treatment should symptoms flare
in the future while offering encouragement about their ability to exercise their new skills
independently
• In some cases, treatment may continue for an indefinite period at a reduced frequency

Evidence basis:
In a RCT, IPSRT during the acute treatment phase was associated with more time prior to
recurrences in the maintenance treatment phase than the comparison intervention
An open label trial IPSRT was effective in delaying relapse than a brief psycho educational
crisis management treatment

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 Transference

Dr Amitkumar Chougule

1. Definition:

➢ “Unrealistic roles or identities unconsciously ascribed to a therapist by a patient during

regression of the psychoanalytic treatment and the patient’s reactions to this
representation derived from earlier experience” (Meninger)
➢ Greenson posits two characteristic features of the transference phenomenon:
1. It is a repetition of the past

2. Inappropriate to the present

2. History of transference

➢ Sigmund Freud’s first clearly psychological use of transference appeared in his 1895
work with Josef Breuer, Studies in Hysteria
➢ In his autobiographical studies, Freud remarked that his concept of transference was
easily recognizable as what the hypnotists called suggestibility
➢ In tandem with this autosuggestion Freud developed the concept of false connection
➢ The false connection was the result of an affectively driven, internal dissociation
➢ A dissociated wish appears during a cathartic session, which had been affectively
driven during an earlier trauma which is a false connection
➢ Transference onto the physician takes place through that false connection because of
the compulsion to associate
3. Importance of transference

• Enable us to penetrate into the past of the patient

• To see how early experiences with important persons have produced a paradigm
around which the individual fashions many present reactions.

• Interpretations, instilling a new insight and appraisal of one’s behavior helps to resolve
the unconscious conflict which is believed to be the pathogenic core of neurosis

4. Types of transference

1. Positive transference:

a. Rooted in patient’s ever-present longing for an idealized parental figure

b. May help the therapeutic work or may hinder it

c. Can be employed to promote in supportive and re-educative therapy

2. Negative transference:

a. Usually found side by side with more positive aspects, reflecting the underlying
ambivalence of the patient’s object relations

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 b. Transfer of hostile feelings towards the therapist, extreme form being seen in
paranoia

5. Transference neurosis:

➢ Earlier relations which were components of neurosis itself also mould, dominating
pattern of patient’s feelings towards the psychoanalyst
➢ This recreation in the doctor-patient relationship of a conflicted relationship with
childhood figure is transference neurosis
➢ In contrast to transference phenomenon, transference neurosis is the sustained
appearance of the transference over time
➢ Salient elements of transference neurosis (Calef 1971):
1. Revival of the infantile neurosis

2. Newness of the illness concentrated upon the relationship to the doctor, and
created out of the frustrated demand for love

3. Dynamic, shifting, changing nature of the symptomatology – it is not a static

concept

4. Displacements and transformations of energy; that essential to the development of

the transference neurosis are the mechanisms of regression and repetition

5. Old symptoms of the adult neurosis lose their libidinal force once transference
neurosis is formed

6. Transference situation in the transference neurosis in not identical and does not
describe in a one-to-one manner the nature of the infantile relationships which have
become transferred

7. Eventually the transference neurosis itself becomes involved in a resistance to

treatment; however, its management permits the undoing of repression and is the
central issue of treatment; this differentiates analysis from other forms of treatment

6. Transference resistance:

➢ The phenomenon of transference resistance holds an unavoidable and central role in

the psychoanalytic process
➢ Freud’s description of transference resistance appears in his technical paper on `the
dynamics of transference`
➢ Early in treatment, one finds generally a positive transference, which is predominantly
conscious, and which expresses itself in friendly or affectionate feelings
➢ As the analytic work progresses, however, and as the effects of the analytic regression
take hold, this situation changes
➢ As the analytic work comes closer to the neurotic conflicts, the resistances increase,
and specific transference resistances are mobilized.
➢ There are at least three ways in which resistance and transference are connected:
1. Resistances against transference
2. Resistances within the transference
3. Transference as resistance

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7. Variants of transference:

1. Narcissistic transference:

➢ The chief mechanism involved in this transference is projection - a relatively

primitive process
➢ Patient projects infantile aspects of his psyche into the analyst
➢ When early developmental stages are involved in transference, the elements that
are projected will reflect the degree of organization characteristic of that stage
➢ A common form of narcissistic transference is characterized by the patient fusing
with the analyst
➢ There are other forms of narcissistic transference where splitting mechanisms play
an important role in addition to projection
➢ Patients may split off what are considered bad aspects of the self-representation
and project them into the analyst
2. Delusional transference, transference psychosis:

➢ It is a situation in which gross anomalies of the patient-therapist relationship

develop
➢ Reider described this as the appearance of psychotic and delusional features in
the transference of a non-psychotic patient
➢ There is disappearance of the ‘as if’ quality of transference
➢ Transference is based on hostility, with the assumption that the analyst is thwarting
rather than promoting cure, and the analyst is supposed to take a sadistic delight
in so doing
3. Eroticized transference, erotic transference:

➢ Usually seen in borderline cases and not in neurotics

➢ Love is predominant so that the patient convinces herself that the analyst is also in
love with her
➢ There is an intense demand for gratification and the productive analytic work
ceases
➢ Such patients refuse to carry on the usual work of treatment and reject
interpretations relating the present feelings to the past and seek no further meaning
and cause of symptoms for which they had presented
4. Transference cure:

➢ Sometimes when a patient gives up his symptoms and attendant anxieties, it may
not be due to a resolution of the transference, but rather because the patient felt
compelled to please the analyst
➢ Freud called such an occurrence a `transference cure`, which should not be
confused with a resolution of the transference

8. Post-Freudian views

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 ➢ A number of confusions exist in regard to the concept of transference as laid down
originally by Freud
➢ Transference implications may be found in all patients reactions both inside and
outside the analysis
➢ When it is the latter, it is not the phenomenon that Freud described
➢ Waelder reemphasized the strict meaning of transference as a regression arising out
of the analytic situation; and if it were not form the analytic situation, the transference
would not be elicited, nor understood
➢ Whatever transference manifestations occur outside the analysis, they have no
analytic therapeutic implications
Anna Freud

• Transference of defence

• Acting in the transference

• Externalization

9. Practical aspects of transference

1. How soon will transference reactions begin?

➢ They can occur in the first session and even before the first session with
fantasies about the therapist and anticipation of what will happen in treatment.
2. What is the true value of transference in psychotherapy?

➢ Transference reactions enable us to penetrate into the past of the patient and
to see how early experiences with important persons have produced a
paradigm around which the individual fashions many present reactions
➢ The therapist often becomes the target of transference projections leading to
resistance in progress of analytic process
➢ Interpretations, instilling a new insight and appraisal of one’s behavior from a
causative perspective should follow
➢ In this way, the therapeutic relationship can act as a corrective emotional
experience
10. Encouraging transference: when to and when not to?

1.Transference may be encouraged in

a. Certain patients whose problems are very deeply repressed and who are
constantly being upset by unconscious conflicts

b. Among syndromes in which obstinate repression may occur are anxiety

reactions, phobic reactions, conversion reactions, dissociative reactions, stress
reactions, and certain obsessive-compulsive reactions

2.Transference should not be encouraged:

➢ When the patient already has a problem in reality-testing (as in psychoses,

unstable borderline cases, and paranoid personalities)

➢ When there is not enough time to work through transferential dependencies

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 ➢ When the therapeutic alliance has not been firmly established to sustain the
rigors of transference

➢ When the defenses of the patient are so fragile that he or she cannot handle
anxiety or tolerate frustration

➢ When the objective in therapy is not deep conflict resolution but, rather, a more
harmonious adjustment to the current reality situation.

➢ When the objective in therapy is not deep conflict resolution but, rather, a more
harmonious adjustment to the current reality situation

11.Differentiate from:

• Working alliance: Patient cooperatively relates to the therapist with expected trust

• Corrective emotional experience: Patient-therapist relationship facilitates restoration

of morale, alleviation of tension, adaptive modes of coping, better understanding and
working through of one’s basic problems

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Sleep Medicine

399
 Discuss the anatomy, physiology and chemistry of sleep

Dr Akshit Shetty
Dr Aparajita Arora
A. Anatomy and neurophysiology of sleep and wakefulness:

Sleep and wakefulness are regulated by separate yet interacting mechanisms.

Sleep Promoting:
1. Anterior Hypothalamus- VLPO (Venterolateral Preoptic nucleus) and
Median Preoptic (MnPO) nucleus- GABA and galanin (Gal)

Wake promoting
1. Posterior Hypothalamus- Lateral and dorsomedial nucleus (orexin producing)
2. Tubermammillary nucleus(TMN)- Forebrain Histaminergic
3. Pedunculopontine tegmental nucleus(PPT) and Laterodorsal tegmental
nucleus(LDT)-midbrain and pontine cholinergic neurons
4. Locus Coeruleus- Norephinephrine
5. Dorsal raphe-serotonin

Wakefulness

During this phase there is high rate of metabolism, increased blood flow and fast
EEG acitivity, with differential gene expression
In the cortex, the more active areas are prefrontal cortex, anterior cingulate parietal
cortex, and precuneus, areas involved with attention, cognition, and memory.

ARAS
The ascending reticular activating system (ARAS), which has afferents from the
pons, midbrain tegmentum and posterior hypothalamus maintains the wakeful state.
Stimulation and lesions to the ARAS, in animal models and clinically, show arousal
and comalike state respectively, but recovery is still possible suggesting that
independent mechanism of wakefulness exist.
The ARAS further has efferents to the thalamus and also separately to the
hypothalamus and basal forebrain, causing cortical activation.

LC
Sends projections from its NE cells directly to most parts of the brain with most
activity during wakefulness (prior to arousal, hence having a causal effect) and
this decreases during NREM, with almost no firing in REM sleep
Responsible for upregulation of plasticity-related genes related to synaptic
potentiation when an individual is awake
Pathways to prefrontal cortex is more active than the one to motor areas, suggesting
that the LC has a more important role to play in decision making as compared to
movements.

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Cholinergic neurons:
a. Pedunculopontine tegmental nucleus(PPT) and Laterodorsal tegmental
nucleus(LDT)
➢ Cholinergic cells from the pons and midbrain are active during awake
states (prior to arousal, hence having a causal effect) and REM sleep,
which reduces in NREM sleep.
➢ Also receive afferents from ARAS and send efferents to the thalamus,
hypothalamus and basal forebrain leading to activation.
b. Basal forebrain
➢ Active during awake states and REM sleep, leading to Ach release by the
basal forebrain leading to cortical activation and is less active in NREM
sleep
➢ Cholinergic neurons of the pons promote REM more than wake, while the
ones in Basal forebrain promote both
➢ Reduction of cholinergic cells in persons with Alzheimer’s Disease, or
Anticholinergic drug use predictably leads to EEG slowing, sedation,
increasing NREM sleep while suppressing REM sleep
➢ Cholinergic agonists (like nicotine) and anticholinesterase inhibitors (like
cognitive enhancers) promote arousal

Tubermammillary nucleus(TMN) of posterior hypothalamus:

➢ First rose to prominence following Constantin von Economo’s findings of
profound somnolence following an outbreak of viral encephalitis (encephalitis
lethargica), which produced lesions to the posterior hypothalamus
➢ The histaminergic neurons send efferents throughout the cortex, being active
simultaneously with awake states (not prior) and inactive in sleep
➢ Histamine infusion causes arousal, whereas lesions of the TMN decrease
waking and increase SWS and REM sleep, being mediated by H1 receptors
by enhancing both glutamatergic and cholinergic transmission

VTA and Substantia Nigra:

➢ Innervate the frontal cortex, basal forebrain, and limbic structures.
➢ Though mean firing rate remains stable in sleep or wake states, there is
increase bursting activity in REM sleep relative to NREM sleep
➢ Lesions lead to loss of behavioral arousal without reduction of cortical
activation, while psychostimulants promote prolonged wakefulness with
increase cortical activation and behavioral arousal
Lateral Hypothalamus:
➢ Hypocretin/Orexin produced by lateral hypothalamus provides excitatory input
to all components of the ARAS, LC, PPT, LDT, VTA, basal forebrain and TMN
➢ Most active slightly prior to and during waking with almost no activity during
both NREM and REM sleep
➢ Stimulation of hypocretin cells promotes arousal from sleep, but not at rate as
fast as cholinergic and noradrenergic cells can
➢ Lesions and mutations to hypocretin genes cause Narcolepsy

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 ➢ Progressive elimination of hypocretin cells leads to evolution of Narcolepsy,
with loss of cells leading to sleep fragmentation first and after loss of more
than 95% leads to cataplexy
➢ Hypocretin cell reduction is see in Parkinson disease, with sleep disturbances
similar to narcolepsy.

Dorsal Raphe:
➢ Serotonergic cells also send efferents widely throughout the cortex
➢ Higher firing at during waking state with lower levels in NREM sleep, and
almost no activity in REM sleep.
➢ Activated during repetitive motor activity such as grooming and feeding and
inactive during orientation to salient stimuli, opposed to what is seen in the
NE system
➢ SSRIs have been shown to decrease sleep time and increase arousal during
sleep
➢ But the role of serotonin in sleep is not as straightforward, with it also being
able to induce sleep by inhibiting cholinergic neurons, albeit not directly,
although they may not maintain sleep.

NREM Sleep

➢ Regulation of NREM sleep, involves interaction between multiple structures

such as the lower brainstem, thalamus, hypothalamus and forebrain
➢ Brain activation decreases in NREM sleep, particularly SWS and there is an
overall decrease in CBF
➢ Functional imaging shows deactivation of most cortical and subcortical
structures, such as brainstem, thalamus, hypothalamus, basal forebrain,
basal ganglia, cerebellum, frontal, parietal and temporal cortical areas
➢ The EEG shows oscillatory waveforms such as sleep spindles, K complexes,
slow waves and slow oscillations.

Thalamo-cortical loops:
➢ Shortly before sleep is induced, there are changes in the activity of ARAS,
cholinergic, noradrenergic, histaminergic, hypocretinergic, and glutamatergic
systems which lead to change in thalamic and cortical neuronal firing
➢ An interplay between intrinsic cellular properties and synaptic activity leads to
sleep oscillations, which is mediated by cortico-cortical, cortico-thalamo-
cortical, and thalamoreticular loops
➢ Thalamocortical cells get hyperpolarized while reticulothalamic cells are
activated, which subsequently also inhibit thalamocortical cells. This is
responsible for sensory stimuli gating at the thalamus and hence not reaching
the cortical centers.

Slow oscillations:
Result of brief hyperpolarization of cortical neurons, seen as a high amplitude
negative wave, found in virtually all cortical neurons
This is associated with an absence of synaptic activity in other cortical networks

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K-complexes:
Largest normal EEG activity
Made up of the cortical depolarization phase followed by its triggered spindle.

Spindles and Delta waves:

Causes due to K complexes and their interaction with the thalamus.

Anterior Hypothalamus -VLPO and MnPO

➢ Stimulation of the anterior hypothalamus resulted in increased slow-wave

activity in the cortex.
➢ Cases of encephalitis lethargica, lesions in the anterior hypothalamus, were
characterized by insomnia.
➢ The VLPO of the anterior hypothalamus is a possible sleep switch.
➢ These neurons release GABA and galanin, inhibiting most wakefulness
promoting areas.

Other GABAergic sites

Apart from other sites in the cortex, the medulla has sleep-promoting GABAergic
cells, which inhibit the parabrachial nucleus, thereby inhibiting glutaminergic
projections to the basal forebrain, promoting NREM sleep

Serotonergic neurons
Inhibits cholinergic systems, have a role in sleep onset, not maintenance of sleep as
is seen by reduced firing in NREM and nil in REM sleep.

REM Sleep

➢ REM sleep is characterized by an activated EEG and increased neuronal

activity and CBF
➢ Functional imaging shows that some brain regions show increased activation,
while others show decreased activation, in comparison to wakeful state.
➢ Mesopontine tegmentum, thalamus, posterior cortical areas and limbic areas
are highly activated during REM sleep, while frontal and parietal lobes are
relatively deactivated
➢ The pons and caudal midbrain are essential for REM sleep, with lesions
eliminating REM sleep
➢ Preoptic area also is involved with regulation and organization of REM
episodes
➢ NREM-REM cycles are explained by reciprocal interaction (Hobson and
McCarley) based on cholinergic and NE system interplay
➢ Cholinergic neurons (REM on cells, active when awake and REM) in LDT &
PPT project to the thalamus and basal forebrain, producing EEG activation
and a hippocampal theta rhythms, while activating the limbic system and
cortex

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 ➢ REM-on cells are inhibited by itself and REM off cells(noradrenergic or
serotonergic, active in awake states and reduced in both REM and NREM)
➢ Cholinergic agonists in LDT/PPT produce prolonged REM sleep and reduced
REM latency
➢ NE and serotonin antidepressants reduce REM sleep, while TCAs and MAOIs
(anticholinergic effect) also suppresses REM sleep
➢ GABAergic and glutamatergic neurons in the mesopontine tegmentum also
play a role in REM regulation
➢ Muscle atonia, can be found in pathological wake states, such as Narcolepsy
(Sleep paralysis and Catalepsy) while when absent in REM sleep leads to
REMBD
➢ Ponto-geniculo-occipital (PGO) are responsible for eye movements and
muscle twitches, activated by cholinergic cells and suppressed by
serotonergic cells

B. Neurochemistry:

Wake promoting- Orexins/Hypocretin, Catecholamines, ACH, Histamine

Sleep promoting-serotonin, Galanin, GABA and adenosine

1. Catecholamines:
➢ Jones B(1972) reported that upon inhibiting catecholamine metabolism,
intense sustained arousal followed, with the converse being true
➢ The Locus coereulus(LC) producing NE is pivotal for wake promoting as part
of the ascending reticular activating system.
➢ The LC sends ascending projections via the ventral pathways to various
forebrain areas
➢ LC is most active during arousal which gradual decline of activity in sleep.
➢ Upon activation of Alpha and Beta-adrenergic receptors in the hypothalamus
and thalamus, there is a transition from slow wave sleep pattern to a tonic
discharge as sleep when awake
2. Orexin/Hypocretin:
➢ Discovered relatively recently-1998.
➢ Prehypocretin is made in the dorsal and lateral hypothalamus, which becomes
Orexin A/ Hypocretin(HCRT) 1 and Orexin B/HCRT 2.
➢ Action via direct effect on postsynaptic receptors and indirectly via local
glutamate release.
➢ Also has effect of cholinergic neurons.
➢ Widespread projections (Siegel ,2004)-
➢ Absence of it leads to unstable switch, with the individual fall asleep at
inappropriate times, as in narcolepsy.
3. Histamine:
➢ Released by TMN
➢ Three histaminergic receptors- HR1 is responsible for arousal, while HR3 –
autoreceptor, negative feedback for histamine
➢ Orexin and histaminergic systems seem to have effects on each other, with
one stimulating the other

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 ➢ VLPO inhibits the TMN as sleep is induced, along with reduced serotonergic
and orexinergic stimulation

4. ACH:
➢ Basal forebrain and pontine cholinergic activity is high in wake and REM states
➢ Cholinergic agonists like nicotine induce cortical activity, increase REM sleep
(but reduces sleep overall) and increases vigilance
➢ Similarly, atropine, a cholinergic antagonist, reduces vigilance, inducing slow
wave activity in EEG

5. GABA-Galanin:
➢ Discovered by Sherrin et al(1996), that VLPO contains GABA and Galanin
➢ At sleep onset, maximal firing of VLPO, as well as NREM
➢ Inhibitory neurons are sent throughout the brain, especially the wake promoting
regions
➢ GABA which is found in the other regions of the brain, behaves differently
➢ For eg, activation of GABA receptors in pontine sleep areas, by inhibiting it,
causes arousal. And when this GABA pathway is inhibited, sleep in induced
➢ Most hypnotics, including barbiturates, benzodiazepines, and several of the
newer nonbenzodiazepine hypnotics act by enhancing GABA transmission
➢ However, many GABAergic neurons in the brainstem and basal forebrain are
active during wake

6. Serotonin:
➢ Produced in the dorsal Raphe, firing rate of which is highest in Wakefulness
and decreases in NREM and is almost nil in REM.
➢ But the effect of serotonin on sleep-wake is complicated due to its interactions
with various pathways, and also that melatonin is a metabolite of serotonin.
➢ Hence, it has been seen that when serotonin catabolism is inhibited, the person
can go to sleep and when production is reduced, can remain awake.
➢ SSRI, which increase synaptic serotonin, disturbs sleep.
➢ Details of the various mechanisms of serotonin are complex and not completely
understood.

7. Adenosine:
➢ Caffeine promotes wakefulness by its inhibitory action on adenosine receptors
➢ Found throughout the brain as a metabolic by product of ATP, levels increase
as a result of increased glutamatergic activity
➢ Administration of Adenosine activates VLPO and inhibits cholinergic neurons,
hypocretin cells and glutaminergic cells, promoting sleep
➢ During wakefulness and sleep deprivation, Adenosine levels build, and acting
as a negative feedback, inhibits wake promoting pathways.

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Other neuractive chemicals which promote:

a. Arousal:
o Substance P
o Neurotensin.
o Epinephrine
o Corticotrophin-releasing factor.
o VIP
o Thyrotropin-releasing factor
o Cortisol
b. Sleep;
o Melatonin
o αMSH
o Growth hormone- releasing factor
o Insulin
o CCK
o Bombesin
o Cytokines (IL-1, IL-6, TNF released during infections promoting sleep then)
o Muramyl peptides(gut bacteria)

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 Chronobiology/ Circadian rhythm

Dr Akshit Shetty
Dr Aparajita Arora
Introduction:
➢ Chronobiology is the study of biological time
➢ The Earth completes one rotation about its axis by 24 hours
➢ Despite having many different rhythms, the circadian rhythm is the most studied and
has a period of 24 hours and 18 minutes.
➢ As there is a difference of 18 minutes, over a period of three months, there is a loss of
day-night phase
➢ Many rhythms, such as core temperature, eating, sleep, hormone levels are based on
the circadian clock

CIRCADIAN PACEMAKERS:

Anatomy:

Hierarchy of pacemakers:

•The suprachiasmatic Nucleus (SCN) is the master oscillator

•Peripheral oscillators:
Present in kidney, liver, lung, heart and other parts of the brain
Regulated by food and exercise
This explains their ability to reset circadian rhythms

Suprachiasmatic Nucleus(SCN):

➢ Small pair of hypothalamic nuclei dorsal to the optic chiasma

➢ Show peak activity during the subjective day, and the fluctuations are inherent to SCN
➢ The neurons of the SCN are relatively small with short dendrites, leading to high
packing density and are immunopositive for GABA

Subdivisions of the SCN:

1. The core- presence of calbindin-positive neurons
2. The shell

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Afferent Projections to SCN:

1. Retino-hypothalamic tract:
➢ Primary afferent input
➢ Small subset of retinal ganglion cells and innervates the entire volume of the
SCN
➢ Glutamate is the primary neurotransmitter
➢ Change in illuminance is most in sync with the Earth’s rotation
➢ Hence, this functions as the most reliable zeitgeber (time giver)
➢ The properties of circadian photoreceptors are different from visual
photoreceptors, so as to be only sensitive to daylight and not other sources
such as moonlight, though some forms of artificial light can still affect it

2. Ipsilateral intergeniculate leaflet (IGL):

➢ A subnucleus of the lateral geniculate complex:
➢ The IGL receives input from the retina directly which is relayed to the SCN
➢ Hence, it is a secondary indirect pathway from the retina to the SCN
➢ Neuropeptide Y is the transmitter

3. Many less well understood pathways, one of which is a serotonergic projection from the
midbrain raphe

Efferent Projections from SCN:

1.Pineal gland (secretes Melatonin):

SCN PVN Thoracic spinal cord Superior cervical ganglion

Pineal gland

➢ The ultimate outcome is that when SCN activity is low (night), melatonin synthesis is
increased
➢ Unlike most other systems, the relationship between the circadian rhythm and
melatonin secretion is relatively straightforward

Exposure to light causes:

I. Acute fall of melatonin level to baseline

II. A phase shift of circadian rhythm
III. As melatonin levels are measurable, it can be used as a marker for circadian phases

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2. HPA axis-

SCN > PVN > Anterior pituitary > Adrenal- secretes Cortisol
(CRH) (ACTH)

➢ Responsible for stress independent cortisol variations with a peak at approximately 6

AM to 8 AM
➢ Cortisol levels are regulated by complex mechanisms, making it less ideal to evaluate
SCN activity

SLEEP AND CIRCADIAN RHYTHMS:

Sleep Regulation:

➢ Sleep is the regulated by:

➢ •Sleep homeostat - based on sleep debt
• Circadian clock
➢ The circadian cycle in arousal (wakefulness) steadily increases throughout the day,
reaching a maximum immediately before the circadian increase in plasma melatonin

Temperature and sleep:

➢ Towards the night, arousal decreases along with core body temperature, and as the
body temperature begins to rise again at around 5-6 AM, and the person is aroused
from sleep about two hours later
➢ Hence for an uninterrupted 8-hour sleep period, sleep has to be initiated at 11-12 PM
➢ Diurnal preference or chronotype:
•Morning type- wake earlier and reach body temperature earlier- advanced circadian rhythm
•Evening type- sleep later and wake later-delayed circadian rhythm

Seasonality in Humans:
➢ There are seasonal variations in birth rate, sexual activity, conception, pain thresholds
and others
➢ Also, variations in growth rate and endocrine regulations exist based on season
➢ Winter brings about a worsening of mood, increased sleep and appetite with reduced
energy and socializing behaviours- Winter blues
➢ As the seasons change, the melatonin patterns are different, leading to season specific
melatonin profiles, though this is hampered by artificial light

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CIRCADIAN RHYTHMS IN PSYCHIATRIC DISORDERS:

1. Seasonal Affective Disorder

SAD is the most evident manifestation of seasonality and illness

Usual onset in the late fall and early winter and remission in late spring and early summer
Also called winter depression, distinct from “winter blues.”
Atypical depression profile is also common, especially carbohydrate craving
Among the general population, the prevalence is between 4 and 9 percent, with 20 % having
sub-syndromal symptoms
Genetic predisposition is present, twin studies showing a 29 to 43 percent for seasonality
and/or SAD
Treatment-
•The gold standard treatment for winter SAD is light therapy, with a fifty percent response rate.
45-90 min daily exposure to broad spectrum ultraviolet-filtered white light source of relatively
high irradiance, with morning being more effective than evening.
•CBT and Antidepressants also are shown to be effective in SAD

2. Unipolar depression:

Abnormal circadian rhythms and diurnal variations have been observed in persons with
depression (Edgar an McClung,2013)
More likely to be evening chronotypes and have reduced peak melatonin levels
Genetic studies reveal, circadian clock genes such as CLOCK and CRY are associated with
depression
Hasler et al(2010) reports on the association between severity of depression and circadian
rhythm abnormalities, normalizing together with mood symptom resolution(Bunney and
Bunney,2012)
Insomnia, commonly seen in depression, is similar to circadian phase shifts which is
associated with RDD (Mendlexicz 2009) and suicidality (Pigeon et al,2012)
Sleep deprivation (Benedetti et al,2007) and Ketamine therapy (Mathews and Zarate2013),
by acting on circadian rhythms, are known to bring immediate relief of depressive symptoms
Advancing sleep phase (Berger et al,1997) and bright light therapy (Oldham et al,2014) also
show benefit in depression
Melatonin administration (Garzon et al,2009) and Agomelatine, melatonin receptor agonist
(Plesnicar, 2014) also have efficacy in depression
Circadian regulation of hormonal (HPA), temperature, and mood rhythms also have influences
on depression

3. Bipolar Disorder:

➢ Bipolar Disorder has been linked to clock genes variants (Roybal et al 2007)
➢ There is a phase delay in Depression, and a phase advance in mania
➢ IPSRT attempts to stabilize these rhythms, reducing circadian abnormalities and
preventing future episodes

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4. Circadian Sleep Disorders:

1. Advanced sleep phase syndrome (ASPS):

Pathological morning chronotype
They typically fall asleep at approximately 7:30 PM and spontaneously awaken at
approximately 4:30 AM
Toh et al(2001) reported an PER2 gene abnormality in an autosomal-dominant familial
form of ASPS (FASPD)

2. Delayed sleep phase syndrome (DSPS):

PER3 gene length polymorphism (Ebisawa et a,2001)
Longer allele-morning chronotype
Shorter allele-evening chronotype.

Bright light therapy has benefits in following Circadian Rhythm Disorders:

1. DSPS
2. ASPS
3. Shift Work Disorders
4. Non-24-Hour and Irregular Sleep–Wake type

5. Memory, Aging, and Neurocognitive Disorders:

a. Memory- Animal studies show knockout of CLOCK genes adversely affecting various
memory functions (Zueger et al,2006)
b. Aging-(Duffy et al,2015) associated with reduced need for sleep, shortening of
circadian rhythm and phase advances
c. Neurocognitive disorders-(Musiek et aal,2015)
Age-related circadian changes are exaggerated in Alzheimer disease (AD), with
severity associated with more fragmented rhythms
Dysregulated circadian rhythms may have predictive value
Light therapy has shown some benefit in AD(Hanford at al,2013)

6. Other Psychiatric Disorders linked to circadian rhythms are:

Ante and Post-Partum Depression
Pre-Menstrual Dysphoric Disorder
Eating Disorders Including Bulimia Nervosa
Attention Deficit Hyperactive Disorder

7. Other Circadian-Clock-Associated Disorders:

Has an effect on other non-communicable disorders such as Cancer, Coronary and

metabolic disorders
Shift workers have higher rates of obesity, low high-density lipoprotein (HDL)
cholesterol levels, and high triglycerides.

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CIRCADIAN RHYTHMS AND PHARMACOTHERAPY
Drugs and circadian rhythms can affect each other
1. Effect of drugs on circadian rhythm:
Antidepressants (Tsuno et al,2005) TCAs and SSRIs:
Improve REM sleep abnormalities
Reduce elevated nocturnal body temperature
Correct the decreased amplitude of daily activity cycles, seen in depression
Enhance the circadian amplitude
Lithium:
Results in a lengthening of circadian period
Glycogen synthase kinase 3β (GSK3β), inhibited by lithium, participates within the
molecular clock mechanism
Short-acting benzodiazepines have chronobiological effects, inducing phase advances
MDMA-Disorganizes activity rhythms

2. Effect of circadian rhythm on drug efficacy and toxicity:

Many chemotherapeutic agents have shown to have 2- to 10-fold changes in tolerability in
rodents over the course of the day, which is attributed to circadian variations of
pharmacokinetic and pharmacodynamic mechanisms

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 Describe the physiology in sleep

Dr Akshit Shetty
Dr Aparajita Arora
PHYSIOLOGY IN SLEEP:

During sleep, most organ systems function differently

Autonomic Nervous System

➢ NREM and tonic phase of REM sleep- parasympathetic activity is more active than
sympathetic
➢ During phasic sleep, increase in both sympathetic and parasympathetic, leading to
autonomic instability

Cardiovascular System

➢ During SWS, least heart rate and blood pressure recording, with less variations
➢ These parameters increase in REM sleep, though not to levels seen in wakefulness
➢ Arrhythmias are more prevalent during REM sleep, hence early morning (more REM
sleep) has increased rate of cardiovascular events
➢ In depression, REM activity is higher, increasing risk for cardiovascular morbidity

Pulmonary System

➢ Reduced sensitivity to CO2 and reducing O2, leading to unstable respiratory drive
➢ Upper airway resistance increases due to muscle relaxation
➢ Hence, there is an increased risk of exacerbation of obstructive lung diseases as well
as sleep apnea disorders

Thermoregulation

➢ Circadian rhythms lead to nocturnal reduction of temperature with increasing temp

heralding arousal from sleep
➢ Sleep has independent effects on temperature

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 ➢ In SWS, the hypothalamic set point is lowered
➢ During REM, there is decreased temperature regulation

Neuroendocrine Changes

➢ As circadian rhythms affect hormonal secretion, during sleep hormonal levels tend to
change
➢ Growth hormone (GH) is released in the early part of sleep, enhanced during SWS
➢ Prolactin- also peaks in sleep, though after GH peak
➢ GH and PRL enhance sleep, SWS and REM respectively
➢ TSH reaches its peak in the evening prior to sleep onset, and is inhibited by sleep and
sleep deprivation stimulates it
➢ The HPA axis is less active at sleep onset, inhibiting cortisol release, and rise in ACTH
and cortisol levels rise before, and possibly leading to, arousal from sleep
➢ Melatonin is only released during the darkness at night
➢ Patients with OSA have decreased levels of GH and prolactin
➢ Sleep deprivation produces evidence of HPA axis and HPT activation.
Sexual Function:

➢ Nocturnal penile tumescence in men and increased vaginal blood flow and clitoral
erection in women during REM
➢ Useful indicator in Sexual medicine to differentiate medical and psychological
causation of Erectile dysfunction

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 Describe the stages of sleep

Dr Akshit Shetty
Dr Aparajita Arora
A. Introduction:
➢ A human sleeps for a third of his life, deprivation or reduction of which can affect
physical and psychological effects.
➢ Sleep and psychiatric disorders overlap as the systems regulating sleep also directly
or indirectly regulate psychological processes.
➢ Also, psychotropic medications have effects of sleep, intended or otherwise
➢ Sleep is a reversible behavioral state of perceptual disengagement from and
unresponsiveness to the environment.
B. Two states of sleep-
1. Rapid Eye Movement (REM)
2. NonRapid Eye Movement (NREM) sleep.
Stages of Sleep:
➢ Within REM and NREM sleep, there are further classifications called stages
➢ Sleep is divided on the basis of a classification by Rechtschaffen and Kales(1968),
which was modified in 2007.

➢ Stage of Sleep:

Wake state:
✓ Beta waves(13-30 hz): EEG shows a low-voltage,fast activity, when eyes are
open.
✓ As the eyes close, alpha activity(8 to 13 Hz) becomes prominent, more so in
the occiput

Sleep occurs in cycles of approximately 90 to 110 minutes and is further divided into-

1. NREM sleep- Non-Rapid Eye Movement Sleep:

o It is called orthodox sleep, and in infants, quiet sleep, due to lack of motoric
activity.
o In between wakefulness and REM sleep.

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 Divided into three stages-
a) N1(previously stage1)- Transitional state
✓ 5% of sleep
✓ 3-5 minutes per cycle
✓ Despite a lower awareness of surrounding(especially visual) and dreamlike
mental activity, subjectively may not be perceived to be asleep.
✓ EEG- Background Beta waves with a few Alpha waves, which are then
replaced by a low voltage, high frequency pattern with prominent theta
waves with vertex sharp waves (V waves) over the central regions.
✓ Skeletal muscle tone reduces, and eye movements become slow
✓ Hypnic jerks or sleep starts may be present, which are sudden muscle
contractions, accompanied by feeling of falling
✓ When sleep deprived, the individual will enter 5-10 second brief periods of
N1, called “microsleep”.

b) N2(Previously Stage 2):

✓ 50% of sleep
✓ 30 minutes per cycle
✓ N2 onwards subjectively perceived as sleep
✓ Eye movements cease
✓ Following N1, EEG is characterized by the appearance of sleep spindles (11
to 16 Hz, lasting ≥0.5 seconds) and K-complexes (high-amplitude,
negative sharp waves followed by positive slow waves), with beta waves in the
background.

c) N3(Stages 3&4):
✓ Also called Slow wave sleep (SWS), Delta sleep or deep sleep
✓ 20-25% of sleep
✓ 20-30 minutes per cycle
✓ Almost no motoric movement
✓ More in the beginning of the night, lesser as the night progresses.
✓ Beta waves are replaced by delta waves, which are slow waves are of 0.5- to
2-Hz frequencies with large amplitudes of >75 μV over frontal regions.
✓ Previously, SWS was subdivided into stage 3(20-50%) slow waves and stage
4 (>50% slow waves), but this is no longer considered to be significant enough
to be separate stages.

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 2. REM sleep, or stage R-Paradoxical sleep and in infants called active sleep:
(20-25% of sleep)
Frequent bursts of eye movement activity.
Divided in terms of tonic (persistent) and phasic (episodic) components.
a. Tonic- Activated EEG alike that in N1 with increased theta activity and decrease
in tone of all muscles but for extraocular and the diaphragm.
Sawtooth waves- triangular 2 - 6 Hz waves may be present.
b. Phasic features -Irregular bursts of REMs and muscle twitches, more as the night
progresses, with intense dreaming.

Discuss the common Parasomnias and sleep related movement disorders

Dr Akshit Shetty
Dr Aparajita Arora

PARASOMNIAS AND SLEEP-RELATED MOVEMENT DISORDERS

Introduction:
➢ Also referred to as disorders of partial arousal
➢ Diverse collection of sleep disorders characterized by physiological or behavioral
phenomena that occur during or are potentiated by sleep
➢ During wakefulness, both the body and brain are active
➢ In NREM sleep, both the body and brain are inactive
➢ REM sleep, however, pairs an atonic body with an active brain (capable of creating
elaborate dream fantasies)
➢ Sleep studies aid in ruling out seizure disorder or a sleep related breathing disorder

1. Nonrapid Eye Movement Sleep Arousal Disorders:

NREM Parasomnia is:

(a) Sleepwalking
(b) Sleepwalking type with sleep-related eating
(c) Sleepwalking type with sleep-related sexual behavior (sexsomnia)
(d) Sleep terror

Sleepwalking:
➢ Individual arises from bed and ambulates without fully awakening
➢ Also called somnambulism, a variety of complex behaviors occur while unconscious
➢ 15 % children, 4-10% adults (Hublin,2003)
➢ 4-8 years of age is peak

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 ➢ Has a familial pattern
➢ Primary parasomnia or secondary to other sleep disorders (e.g., sleep apnea)
➢ When compared to wake walking individuals, sleepwalking would have activation of
cerebellum and posterior cingulate cortex and a deactivation of frontal and parietal
association areas (Bassetti et al, 2000)
➢ Sleepwalking usually occurs during NREM slow-wave sleep, 15 minutes to 2 hours
after sleep onset
➢ Sleep deprivation and disruption of slow-wave sleep exacerbate or precipitate
sleepwalking
➢ From sitting-up, attempting to walk to more complex semi-purposeful actions
➢ While there is relative awareness of environment, more often they end up physically
hurting themselves, eg walking onto a road
➢ There are even reports of violence while sleepwalking
➢ They are difficult to awaken, often confused if awakened
➢ Aggressive awakening is not recommended as it usually terrifies the person, rather
gently take them back to a safe place.

Sleep Terrors (Pavor nocturnus):

➢ Sudden terrified screaming with intense autonomic arousal and fearfulness
➢ 3% children, 1% adults
➢ Hublin (2003) reports a genetic factor in parasomnia.
➢ Severity ranges from less than once per month to almost nightly occurrence
➢ In adults, there is usually a comorbid psy illness or significant traumatizing event
➢ Similar to sleepwalking, usually arise from slow-wave sleep.
➢ Fever and CNS depressant withdrawal potentiates sleep terror episodes
➢ Abnormally low delta wave and frequent brief EEG-defined arousals, not associated
with clinical wake states, on PSG
➢ Usually sits up in bed, screaming and is unresponsive to stimuli, with amnesia
➢ If awakened, the individual is confused or disoriented
➢ No elaborate dream sequences as in nightmares.

Sleep-Related Eating Disorder:

➢ Eating may become obsessional and several small meals may be eaten during the
course of one night
➢ The food consumed or preparation of the same maybe hazardous
➢ The individual may be unaware of the activity and weight gain can become a problem
➢ Partial or complete amnesia

2. REM sleep disorders

Nightmare Disorder:
➢ Nightmares are frightening or terrifying dreams.
➢ Produce sympathetic activation and ultimately awaken the dreamer
➢ Common in children 3 – 6 years (prevalence 10 - 50 percent) and rare in adults (1
percent or less)

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 ➢ Nightmares occur in REM sleep and usually evolve from a long, complicated dream
that becomes increasingly frightening
➢ Having aroused to wakefulness, the dream content is typically remembered
➢ Traumatic events are known to induce nightmares, sometimes immediately but at
other times delayed. The nightmares can persist for many years
➢ Can be recurrent and when occurring in association with posttraumatic stress
disorder they may be recollections of actual events
➢ If frequent and distressing can cause insomnia due to fear
➢ Though can happen in normal individuals, schizotypal, borderline, and schizoid
personality disorders have a prevalence of nightmares and also in schizophrenia
➢ L-DOPA, Beta blockers, withdrawal from REM suppressant medications and drug or
alcohol abuse is associated with nightmares

Rapid Eye Movement Sleep Behavior Disorder:

➢ Failure to have atonia (sleep paralysis) during stage REM sleep, leading them to
literally enacts their dreams
➢ REM-related hypopolarization of alpha and gamma motor neurons leads to
immobilization, without which there can be punching, kicking, leaping, and running
from bed etc
➢ Correlated with dream imagery and not aware of surroundings as in sleep walking
➢ Individuals and bed partners frequently sustain injury
➢ RBD may result from diffuse hemispheric lesions, bilateral thalamic abnormalities or
brainstem lesions
➢ A wide variety of drugs(TCA, SSRI, alcohol and sedative withdrawal) and comorbid
conditions(synucleopathies) can precipitate or worsen RBD
➢ Clonazepam has shown efficacy in RBD.

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 Describe the sleep abnormalities seen in Psychiatric and neurologic disorders
Sleep and psychiatry

Dr Akshit Shetty
Dr Aparajita Arora
Introduction:
➢ Sleep and dreams have been an important area of study with relevance to psychiatric
disorders
➢ Psychoanalytical thinking put great emphasis on the interpretation of dreams and
related psychopathology
➢ Sleep abnormalities are also seen in virtually all other psychiatric disorders, particularly
disturbances in sleep continuity, including prolonged latency to sleep onset, diminished
efficiency of sleep, and decreased amounts of total sleep

1. Mood disorders and sleep

A. Unipolar depression:
➢ Most research regarding sleep and psychiatric disorders have been done in
depression
➢ Sleep disturbances are part of diagnostic criteria for depression
➢ Cholinergic–monoaminergic imbalance hypothesis of depression explains
sleep disturbances leading to increase in REM sleep and reduction in SWS that
is seen in increased cholinergic activity states
➢ Reduced REM sleep latency and loss of SWS are trait markers for depression,
along with decrease in total sleep time, terminal insomnia (more typically, but
also initial and middle), bad dreams or poor quality of sleep
➢ They occasionally persist even in remission and are more prevalent in first-
degree family members
➢ Atypical depression can present with hypersomnia
➢ Also, sleep disorders can lead to depressive disorders
➢ 31% of persons with insomnia and 25% persons with hypersomnia have
depression (Breslau et al,1996)
➢ Also, insomnia is predictive of a depressive episode, which when resolved
reduces the risk of depression. (Chang et al,1997)

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 ➢ Insomnia is an independent risk factor for suicide (Turvey et al, 2002)
➢ There is a reduction in REM latency most commonly (Benca et al, 1992) along
with increased REM density (Waller et al,1989)
➢ But overall there is an increased Sleep latency and increased Wake after Sleep
Onset(WASO) (Gilin et al,1979)
➢ MAO inhibitors, TCA and ECT are REM suppressors (Wyatt et al,1991)
➢ SSRI and other newer antidepressants have less effect on sleep

B. Bipolar disorder:
➢ Insomnia can cause mania which worsens insomnia
➢ Sleep onset latency and increased WASO is seen in mania
➢ Lithium increases slow wave sleep and increases REM latency as well as reducing
REM sleep (Kupfer et al1974)
Sleep deprivation and mood disorder:

i. Sleep deprivation is well known to precipitate mania (Wehr et al,1982)

ii. Antidepressant effect with peak next afternoon in 50% patients (Post et al,1976),
but can be reversed by recovery sleep (Vogel et al, 1975), normalizing the
increased metabolic activity in the anterior cingulate gyrus in individuals with
depression, like antidepressants do.

2. Anxiety and sleep:

➢ Central to anxiety disorder is the activation of the sympathetic nervous system,
causing sleep disturbances among other symptoms
➢ Accordingly, Breslau et al(1996) reported that anxiety disorders are the most
common comorbidity of insomnia, occurring in 24-36% of them and persons with
insomnia are more likely to develop anxiety disorders, compared to normal.
➢ Amongst anxiety disorders, GAD, PTSD and Panic disorder is more likely to cause
sleep disturbances, when compared to OCD
➢ More than 50% of persons with GAD have both initial and middle insomnia (Monti
and Monti,2000)
➢ Though persons with Panic disorder are more likely to have middle insomnia than
normal (Mellman, Uhde,1989), night panic attacks (sudden awakening in NREM)
are more distressing (Uhde,2000)
➢ Disturbance of sleep is considered a hallmark of PTSD (Ross et,1989), commonly
reporting initial insomnia and nightmares.

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 ➢ Also associated with OSA, REM Behaviour disorder and periodic leg movement
disorder (Husain et al, 2001)

3. Schizophrenia and sleep:

➢ With the discovery of REM sleep, given its similarities with the psychotic
experience, a link was studied (whether dream like states were intruding into
wake states), but there was no evidence to support that hypothesis.
➢ Though REM sleep, like schizophrenia, is also shown to have decreased
activity in the DLPFC.
➢ Initial and middle insomnia is common in acute exacerbations (van Kammen et
al, 1986)
➢ Nightmares and hypnogogic hallucinations can be common
➢ Reduced REM latency (Zarcone et al, 1987), increased sleep latency (Zarcone
et al, 1997) and reduced N3(Feinberg et al,1969)
➢ Massimini et al(2009) reported a loss of spindle activity and reduction of slow-
wave activity in persons with schizophrenia, which may indicate a dysfunction
in the thalamocortical network.

4. Alcohol and sleep:

➢ Alcohol use shortens sleep latency and increases NREM but at the behest of
reduced REM (Lobo and Tifik. 1997)
➢ Hence it is often used as a sedative.
➢ As dependence develops, withdrawal related sleep disturbances set in, with
increased sleep latency and reduced total sleep time.
➢ It also has induces sleep disorders, which can be seen even two years after
abstinence (Drummond et at 1988).
➢ Hence, medications for sleep may be required post withdrawal as well, though
BZD and Non BZD hypnotics are avoided due to a possibility of cross tolerance
➢ Diminished SWS, short REM latency, increased sleep latency, increased eye
movements in REM are predictors of relapse (Gilin et al, 1994).

5. Neurological disorders and sleep

A. Dementia and sleep:

➢ The role played in aetiology of vascular dementia is unclear

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 ➢ Similarly, persons with dementia have benefits by treating the primary sleep
disorder
➢ DLB has increased risk of developing REMBD (Boeve et al,2001), which is also
seen more commonly in synucleinopathies(like MSA and PD), in all of which
REMBD develops years before cognitive decline
➢ Clonazepam is the drug of choice.(Maganti et al,2006), with carbamezpine
having some evidence(Touchon et al,1991)
➢ Hypersomnia is common in persons with dementia, usually due to sleep apnea,
circadian rhythm disturbances, medication side effects, nocturnal movement
disorders.
➢ Insomnia is also common in dementia, with comorbid psy illness and
medication side effects being the usual aetiologies
B. Movement disorders and and sleep:

➢ Sleep apnea is more common in persons with Parkinson’s than normal

individual, with improvement in quality of life and symptoms when OSA is
managed.
➢ MAO inhibitors used in PD, can have a stimulant effect causing insomnia.
➢ Insomnia (Middle insomnia most commonly)(Montplaisir,1997)-Apart from the
disease itself, which causes immobility and difficulty turning when asleep ,
primary sleep disorders are more common.
➢ Hypersomnolence can be caused by medications such as Dopamine agonists,
as well as primary sleep or psy disorders.
➢ Parasomnias- as mentioned earlier REMBD often predates PD symptoms
(Boeve et al,2001)
C. Epilepsy and sleep:

➢ Miller et al(1996) reported that 66% of persons with epilepsy had sleep
complaints
➢ With 68% of them feeling sleepy during the day, 29% with initial or middle
insomnia
➢ 42% felt it affected their daytime performance
➢ Drug induced, comorbid, illness related (Touchon et al,1991) including
nocturnal epilepsy, frontal lobe epilepsy, circadian rhythms due to sedentary
lifestyle of most with seizure disorder.
➢ Sleep disorders are more common in Epilepsy (Malow et al, 1997)
➢ Most anticonvulsants cause drowsiness with some causing insomnia such as
LTG and ETX

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Epilepsy during sleep:

1. Myoclonic epilepsy- soon after arousal

2. Nocturnal Paroxysmal dystonia
3. AD Nocturnal frontal lobe epilepsy
4. Benign rolandic epilepsy
5. Panayiotopoulos syndrome

Psycho-
Neuro-
Endocrinology

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 Describe in detail about Hypothalamo-Pituitary-Adrenal axis and its
relevance in the causation of various psychiatric disorders

Dr Akshit Shetty
Dr Aparajita Arora

Introduction:
➢ In 1927, Philip Smith discovered that the pituitary gland produced hormones that
stimulated the adrenal cortex, thyroid, and gonads and stimulated growth
➢ Hence, the Pituitary came to be known as the master gland
➢ In 1933, Hinsey and Markee found that hypothalamic neurohypophyseal hormones
might control the secretions of the anterior pituitary, which has later been confirmed
hence claiming the title of “master of the master gland”
➢ The adrenal gland is the end organ in the HPA axis which upon stimulation from above
releases hormones
➢ The HPA axis forms a vital endocrine system which are responsible for a host of
actions
➢ With respect to this system, the specific chemicals released by the hypothalamus,
anterior pituitary and the adrenal gland are CRH, ACTH and cortisol respectively

In the face of physical and psychological stress, CRH, ACTH and Cortisol are raised.
They are not only vital for homeostasis but also regulate-
1. Glucose & lipid metabolism
2. The immune system
3. Flight or Fright response
4. Responses to novel stimuli
5. Development
6. Stimulus habituation and sensitization
7. Pain
8. Sleep
9. Memory storage

Hence it is no surprise that the HPA system has been the center point of
psychoneuroendocrine research

Cortisol release by the adrenals are controlled by the following:

1. Circadian rhythm
2. Stress responsive circuit
3. Negative Feedback control

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Inhibitory feedback of glucocorticoids on release and synthesis of CRH and ACTH:
1. Immediate- Rate-sensitive regulate only release of both
2. Intermediate- After 1 to 2 hours, is dose and duration-sensitive, inhibits the release of
both as well as the synthesis of only CRH
3. Slow/Delayed->2 hours decreased synthesis of both

Most psychiatric disorders have abnormalities of this feedback process:

Effect of other neurotransmitters of the HPA axis:
1. Glucocorticoid release is amplified by serotonergic and cholinergic input
and is inhibited by GABA and opioids
2. Catecholamines play a role in response to stress and interact with the limbic–
hypothalamic–pituitary–adrenal axis

Pathophysiology of HPA axis alteration and stress:

Stress leading to activation of the HPA axis, which aids in dealing with it.
But chronic stress, which is an etiological factor in mood disorders, alters the HP axis leads to
many more changes, such as

1. Increases in CRH
2. Reduction in CRH receptors in the anterior pituitary, hence reduced ACTH response
which manifest as ACTH concentrations initially increasing and then diminish over time

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 3. Increased activation of the locus coeruleus, increasing noradrenergic drive which
explains increase in arousal and selective attention and also decreases vegetative
functions
4. Local excitability decreases inhibiting the positive effects of stress responsive
hormones
5. Failure to suppress cortisol in response to dexamethasone or CRH
6. Increased adrenal size and sensitivity to ACTH
7. Increased cortisol in hippocampal cells can lead to cell death, impairing cortical cortisol
negative feedback
8. Reduced Glucocorticoid receptors, leading to diminished feedback

Similarly, exogenous corticosteroids following an initial activation, eventually, especially higher

doses
Also, corticosteroids have multiple regulatory effects on serotonergic function and
on mesencephalic dopamine transmission

HPA and Psychiatric disorders:

HPA axis abnormalities are associated with Psychiatric disorders, such as:
1. Depression
2. Psychosis
3. PTSD
4. Substance use
5. Psychosis
6. Borderline Personality disorder

1. Depression:

➢ Corticosteroids have multiple regulatory effects on serotonergic function and

on mesencephalic dopamine transmission which have a basis in depression
➢ Parker et al, 2003, found functional abnormalities in the HPA axis, such as cortisol
hypersecretion in 50-70% of persons with depression
➢ Holsboer found a reduced peripheral GR sensitivity (Holsboer, 2000)
➢ One important finding is that cortisol levels after dexamethasone (DEX) administration
are less suppressed in MDD (Ising et al., 2005)
➢ This reduced feedback sensitivity has been interpreted as reflecting an exaggerated
CRF drive (Nemeroff, 1996) and/or as a reduction of GR functioning (Holsboer, 2000)
➢ In depressed patients, the ACTH/cortisol response to the combined DEX/CRH test is
significantly increased compared with controls
➢ The combined DEX/CRH test, measuring HPA dysfunction, is sensitive (80%) for
severe major depression (Heyser et al,1994)
➢ Reduced hippocampal volume in persons with depression (Heim and Binder, 2012)
➢ When clinical outcomes were studied:
• DEX/CRH test normalization either precedes or coincides clinical recovery, and
absence of which showed poor prognosis (Holsboer et al 1991)
• Severe HPA dysregulation had higher relapse rates within 6 months as opposed
to persons who had less dysregulation (Zobel et al,2001)

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 • Good response early (after 1 - 2 weeks) and at 6 weeks to treatment are associated
with less HPA system dysregulation (Hatzinger et al,2002)

Genetic studies revealed:

➢ Reduced Glucocorticoid Receptor(GR) mRNA in persons with depression. (Webster

et al.,2002)
➢ Increased methylation(hence inhibition) of the GR gene promoter (McGowan et
al.,2009)
➢ Polymorphisms in GR gene are associated with depression (Binder et al)
o Eg Heterozygous carriers of the 9 beta G allele associated with relative GR
resistance (Kumsta et al., 2007)
o Even mineralocorticoid receptors (MR) have a role to play in HPA axis and the
stress response (Reul et al., 2000)
o In conclusion, the evidence suggests an exaggerated CRF drive and/or
reduced GR functioning in depression

➢ More than half of persons with Cushing syndrome (Starkman et al,1981) have
disturbed mood with one tenth having suicidal ideations or psychotic symptoms. They
similar cognitive deficits as seen in depression
➢ Mood symptoms in them improve with reductions of cortisol levels, by drugs such
Mifepristone and ORG34517 (Reus and Wolkowitz, 2001) and such findings were also
found in person with independent mood disorders
➢ Even reduction of cortisol levels such as in Addison disease (Starkman et al,1985) one
can develop depressive symptoms, which again is ameliorated upon correction of the
deficiency
➢ Barden (2005) reported antidepressants could exert their clinical action in depression
via the restoration of type II glucocorticoid receptor function with a subsequent
reestablishment of HPA axis negative feedback
➢ Lithium, carbamazepine and valproate inhibits the Glucocorticoid Receptors which
may explain their therapeutic effects
➢ CRH-1 antagonists are being developed as potential pharmacotherapies for
depression. (Holsboer and Ising,2008 kehne 2007)

2. HPA and Psychosis including schizophrenia:

➢ In schizophrenia, difficulty suppressing cortisol after dexamethasone is associated with

negative symptoms and cognitive impairment
➢ By moderating cortisol induced damage to the hippocampus, Clozapine has been
shown to improve cognitive functioning, reversing stress induced LTP deficits
➢ Persons with Schizophrenia who have polysdipsia show marked impairment in cortisol
suppression of ACTH

3. HPA and substance use:

➢ Steroid induced acute enhancement of dopamine activity has a role in motivation and
drug use

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 ➢ Alcohol use disorders produce profound changes in HPA regulation
➢ Pseudo-cushingoid features are seen in following chronic alcohol use intake
➢ There is also suggestive evidence that alteration in HPA response to acute alcohol
challenge may represent an endophenotype of genetic risk of dependence
➢ CRH plays a role in substance relapse following stress

4. HPA and PTSD:

➢ Associations of abnormalities in HPA activity, hippocampal volume, and memory

functions are present
➢ Low cortisol concentrations might be a pre-existing risk factor for developing PTSD
(Yehuda, 2002)
➢ They tend to have low cortisol and ACTH levels despite high CRH activity/exogenous
CRH administration (Heim and Nemeroff,2009) and enhanced suppression by DEX.
(Yehuda 2002)
➢ A reduced hippocampal size in persons with PTSD (Karl et al., 2006, Wingenfeld et
al., 2010)
➢ Considered previously as a consequence of illness, but now being seen as a risk factor
➢ (Gilbertsonet al., 2002).

Borderline Personality Disorder:

➢ Comorbid MDD and PTSD, play an important role in HPA alterations in BPD
➢ Contrary results have been seen, hence is hypothesized that there are at least two
subgroups of BPD patients:
• Trauma-associated symptoms with no HPA dysfunction or even enhanced
functioning
• With mood disturbances having HPA axis dysfunction (Wingenfeld et al., 2010)

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 HYPOTHALAMIC–PITUITARY–GONADAL AXIS

Dr Akshit Shetty
Dr Aparajita Arora

Introduction:

➢ The cell bodies of GnRH are located principally over the optic chiasma in the arcuate
area, with projections to the median eminence, and in the lamina terminalis
➢ GnRH leads to release of LH and FSH from the pituitary
➢ GnRH release is stimulated by norepinephrine and inhibited gonadal steroids via
negative feedback
➢ The gonadal hormones are steroids, secreted mainly by the ovary and testis, but also
by the adrenal cortex as well
➢ The prostate and adipose tissue have a role in synthesis and storage of
dihydrotestosterone
➢ These hormones play a pivotal role in the developmental process, specifically the
sexually dimorphic CNS structures and functions, for eg. size of the hypothalamic
nuclei and corpus callosum, the organization of language ability etc
➢ Administration of GnRH can result in a depressive-like state, which is possibly due to
the hypoestrogenic state it induces
➢ By reducing testosterone, GnRH analogs have some role in paraphilias
Testosterone:

➢ Testosterone is the primary androgenic steroid

➢ It facilitates male gonadal development and linear body growth, as well as sexual
desire in both genders
➢ Clinical role of Testosterone:
1. Abnormal levels are seen in schizophrenia, PTSD, depression, and anorexia
nervosa
2. Testosterone has shown benefit in late life depression (Perry et al 2002) and
in refractory depression (Pope et al, 2003)
3. Rabkin et al (2000) reported its effects in alleviating depressed mood, anergia,
reduced libido in men with HIV
4. Anabolic steroid administration lead to both euphoria, increased energy, and
libido and also to irritability, mood swings, violent feelings, anger, psychotic
symptoms and hostility (Nakatani et al,1995)
Dehydroepiandrosterone:

➢ DHEA and DHEA-S are adrenal androgens secreted in response to ACTH, and is also
made in the brain
➢ They are the most abundant circulating steroids
➢ Clinical role of DHEA:

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 1. Leads to improvement in mood, energy, libido, and functioning persons with
depression. (Piexoto et al,2014)

2. Improves mood, energy, and sexual functioning in women with Addison’s disease
(Coles et al,2005)

3. Mood, fatigue, and libido improved in persons with HIV-positive patients treated
with DHEA (Rabkin et al,2000)

4. DHEA administration improved EPS in person with schizophrenia antipsychotics

(Nachscloni et al,2005)

Estrogen and Progesterone:

Estrogen:

➢ Estradiol (E2), estrone (E1), and estriol (E3)

➢ Explains Gender differences in clinical profiles
➢ Depression which is more prevalent in women, can be attributed to hormonal changes
at menarche, along with other such periods of hormonal dishevel such as Postpartum,
peri-menopause and premenstrual
➢ Evidence suggests that estrogen therapy is therapeutic in both severe postpartum
depression (Gregoire 1996) and perimenopausal depression (Gordon et al 2014)
➢ Even women with bipolar disorder are sensitive to gonadal steroid alterations
➢ The benefit of stress reduction during pregnancy due to Oxytocin and Prolactin is lost
in the post partum period, increasing risk of psychiatric illnesses, especially if the
mother doesn’t lactate, which is again protective against mood disturbances
➢ Prophylactic estrogen administration has been reported to prevent recurrence of
postpartum depression
➢ A chronic estrogenic state leads to poor response to SSRI (serotonin receptors is
partially estrogen dependant), which is ameliorated by low dose estrogen augment of
SSRI’s(Parry 2010)
➢ There is an association between psychotic symptoms and antipsychotic side effects
with and phases of menstruation, which is mediated by estrogen.(Seeman 1996)
➢ Lower levels of estrogen are associated with positive, negative and cognitive
psychopathology in schizophrenia
➢ Peri and Serio(2008) conclude that estrogen has scope for efficacy in the management
of Alzheimers disease
Progesterone:

➢ Progesterone is produced by the corpus luteum of the ovary

➢ It also counteracts the mood elevating properties of estrogen when given as a
combination for perimenopausal depression (given to prevent estrogen induced
endometrial hyperplasia)
➢ Premenstrual dysphoric disorder occurring in the luteal phase, disappearing within a
few days of the onset of menses is postulated due to progesterone induced decreased
serotonin uptake
PREGNENOLONE AND ALLOPREGNANOLONE

➢ Pregnenolone is a neurosteroid synthesized from cholesterol in the brain, can be

metabolized in progesterone as well as other steroids

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 ➢ Allo is a neurosteroid derived from progesterone with high concentrations in the CNS
➢ They modulate activity at various neuroactive receptors such as GABA, NMDA, σ-1,
5-HT3, nicotinic, kainate, oxytocin, and glycine
➢ Testosterone-induced Down regulation of allo leads to aggression in mice, attenuated
by administration of fluoxetine, progesterone and estrogen (Pinna, 2005)
➢ Post SSRI increase in CSF allo is associated with clinical improvement. (Uzunova et
al, 1998)
➢ Though not available for clinical use yet, trials are ongoing

PROLACTIN:

➢ Dopamine is called the Prolactin Inhibiting Factor(PIF) because of its action on the
tubero-infundibular pathway
➢ Hyperprolactinemia is associated with:
1. Reduced libido in men and women

2. Depression and anxiety

➢ Severity of TD (Souza 2011), positive (Rajkumar 2014) and negative symptoms (Ates
2015) are correlated with PRL levels, though a definitive association is unclear.

PARATHYROID HORMONE:

Hyperparathyroidism is associated with-

1. Stupor and coma

2. Delirium
3. Depression
4. Psychosis
5. Anxiety
Hypoparathyroidism by causing changes in Calcium and magnesium levels leads to:

1. Cognitive impairment
2. Psychosis
3. Depression
4. Anxiety
GROWTH HORMONE:

➢ Required for normal growth, made and released by anterior pituitary gland
➢ Adult patients with GH deficiency tend have atypical depression, which improves with
GH therapy (Mahajan et al,2004)
➢ GH abnormalities are well known in Anorexia, though it is probably secondary to other
endocrinal abnormalities (Gianotti et al,2002)
➢ GHRH has shown to stimulate food consumption in eating disorders (Vaccarino and
Black,1994)
SOMATOSTATIN:

➢ Somatostatin (Somatotrophin Release Inhibitng Factor, SRIF) is a hypothalamic

secretion from the PVN

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 ➢ Abnormal SRIF is associated with neurodegenerative disorders such as AD,
Parkinson’s, MS and Huntington’s

ARGININE VASOPRESSIN:

➢ Posterior pituitary hormone

➢ Released by pain and emotional stress apart from dehydration
➢ Altered AVP function has been reported in depression (Neumann 2012)
➢ Hypersecretion of centrally AVP is seen in eating disorders (Frank et al 2000)
➢ Chronic psychiatric patients have polydipsia secondary to inappropriate secretion of
AVP
➢ Fluoxetine treatment of depression decreases the CSF vasopressin (de Bellis et al,
1993)

OXYTOCIN:

➢ Oxytocin is a posterior pituitary hormone

➢ Also called the amnestic neuropeptide owing to it’s ability to impair memory
consolidation and retrieval
➢ Children autism have been reported to have reduced levels of oxytocin and less than
expected increases in oxytocin as per age
➢ Oxytocin receptor gene is associated with autism (LoParo D et al, 2015)
➢ Trials for efficacy are ongoing
➢ Oxytocin is associated with anorexia, though further study in this area is required
(Maguire et al 2013)
NEUROPEPTIDE Y:

➢ NPY is synthesized in the arcuate nucleus of the hypothalamus

➢ Cannabis use increases NPY-1 receptor levels, increasing craving for carbohydrates
➢ Antidepressants, ECT and lithium are known to increase NPY concentration
➢ Certain NPY gene polymorphisms are associated with alcohol dependence (Spence
et al,2005) and depression (Morales-Medina 2010)
INSULIN:

➢ Atypical antipsychotics are known to increase insulin resistance increasing the risk of
developing diabetes, though psychotic stress itself may impair insulin sensitivity
➢ TCA’s are also known to increase insulin resistance, whereas SSRI’s are known to
increase insulin sensitivity, hence preferred in persons with comorbid DM
CHOLECYSTOKININ:

➢ CCK is a peptide neurotransmitter originally isolated from the gut

➢ Known to modulate dopaminergic systems
➢ It has shown clinical use in:
1. Schizophrenia:
Though CCK levels have been found to be low in Schizophrenia, trials of agonists
have so far not found positive results
2. Substance use:
CCK activity on the CNS has been associated with substance use hence there is
a potential use for CCK receptor antagonists in the treatment of drug dependence.

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NEUROTENSIN:

➢ Neurotensin plays a role in neuroendocrine regulation, such as the serotonin,

dopaminergic, GABAergic and glutaminergic pathways, as well as the HPT axis
➢ CSF neurotensin is low in persons with schizophrenia which increases upon
antipsychotic administration
➢ It also is linked with the development of antipsychotic induced movement disorders
➢ This suggests that neurotensin receptor agonists may be candidates for the treatment
of psychosis and attenuate dopamine-induced motor behaviors (Kinkead et al, 2004)
➢ Via it effects on the dopaminergic system in the nucleus accumbens, has a role in the
development of drug dependence

HYPOTHALAMIC–PITUITARY–THYROID AXIS

Dr Akshit Shetty
Dr Aparajita Arora

Introduction:

➢ In 1927, Philip Smith discovered that the pituitary gland produced hormones that
stimulated the adrenal cortex, thyroid, and gonads and also stimulated growth
➢ Hence, the Pituitary came to be known as the master gland
➢ In this axis, the hypothalamus secretes TSH
➢ In 1933, Hinsey and Markee found that hypothalamic neurohypophyseal hormones
might control the secretions of the anterior pituitary, which has later been confirmed
hence claiming the title of “master of the master gland”
➢ The TRH released by it acts on the Pituitary releasing TSH
➢ The thyroid gland is the end organ in this axis, secreting two thyroid hormones: T3
and T4
➢ T3 is the more potent and is majorly synthesized by the peripheral conversion from
T4
➢ T3 and T4 then act on both the pituitary and the hypothalamus to inhibit TSH and
TRH, respectively as part of negative feedback
➢ Prepro-TRH 178–199, a derivative of TRH, has been identified in rats to behave
as corticotropin-release-inhibiting factor (CRIF), inhibiting the synthesis and
secretion of ACTH
➢ This has a role in integrating the HPA and HPT axes

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Relationship with other organ systems

1. A role in the development and regulation of almost all organ systems

2. Regulates all other major hormones
3. Regulate transcription of a variety of genes
4. Specifically, with respect to the neurohumoral system-
• Noradrenergic systems stimulate TSH secretion, while dopaminergic systems
inhibit the release of it
• Thyroid hormones decrease NE release and increase Adrenergic receptors
• TRH has direct effects on cholinergic and dopaminergic systems

Blunted TSH response is found in many disorders:

1. Mood disorders
2. Anxiety disorders
3. Alcohol use disorder
4. Eating disorders
5. Schizophrenia

Hence, persons with thyroid disorders often have psychological symptoms accompanying the
physical symptoms, being associated with inducing almost all psychiatric symptoms or
syndromes

Not uncommonly primary presentation is with psychological symptoms.

So much so, that a thyroid function test, if not done almost routinely, is invariably done in the
setting of an atypical psychiatric presentation

435
Depression:
➢ According to studies by Jackson (1998) and Loosen and Prange (1982), depression is
associated with-
1. Mild elevation of serum thyroxin (T4)
2. Blunted TSH response TRH
3. Loss of the nocturnal rise in TSH
➢ Duval et al (1990) reported that TRH-TSH test done at 11 PM was more sensitive than
done at the 8 AM
➢ The difference in TSH response between 11 PM and 8 AM TRH tests was an even
more sensitive measure
➢ This chronobiological index is reduced in about 80% of major depressed in-patients
(Duval et al ,1994, 1996,1999)
➢ Basal T3 level is inversely related to period for episode recurrence
➢ Basal TSH is positively correlated with overall severity of depressed mood
➢ Low CSF transthyretin is seen in persons with depression

Predictive value of the TRH test:

Duval et al(2006) found that following remission, Blunted TSH response can either:

1. Normalizing- Suggesting that it is state dependent

2. Persisting-Suggesting that it is trait dependent or a vulnerability

Effects of antidepressants on the HPT axis:

➢ Low evening TSH secretion (Duval et al,1996) and higher T4 levels (Linnoila et
al,1982) have the low response rate to antidepressant, suggesting that thyroid
hormones can amplify effects of antidepressants
➢ Regarding the effect of antidepressant on HPT axis the results are mixed.
➢ Loosen (1992) amongst others reports a reduction of thyroid hormone levels and
increased TSH levels
➢ It is unclear whether drugs have a direct effect on the HPT axis or the changes occur
with recovery, the latter being more likely
➢ Rosembaum et al(1993) showed chronic antidepressant treatment decreases thyroid
function in animal studies.
➢ However, Laakmann et al (1990) showed that tricyclic antidepressants have no
consistent effect on TSH secretion in normal population
➢ Even in persons with depression, treatment with tricyclics, SSRIs or MAOIs do not
induce significant changes in TSH levels
➢ Supraphysiological dosing (200 to 500 μg per day) has been tried as an adjunct in
treatment-resistant depression and intractable bipolar disorder
➢ T3 increases 5-HT in frontal cortex and induces downregulation of 5-HT1A
autoreceptors possibly explaining the therapeutic efficacy of supplemental thyroid
hormone in treatment-resistant depression

Hypothyroidism and Psychiatric disorders:

➢ As mentioned above, hypothyroidism is associated with a host of psychiatric

presentations

436
 ➢ Hypothyroidism impairs neurogenesis in the hippocampus
➢ Typically, the presentation is one of fatigue, memory loss, irritability, reduced libido
though syndrome of depression, psychosis or dementia can also develop
➢ Usually in milder or subclinical forms of hypothyroidism, due to lack of overt symptoms,
often primary psychiatric conditions are diagnosed and treated
➢ Hence, a thyroid function test is necessary to properly manage the clinical picture
➢ Upon rapid normalization of thyroid status, manic symptoms have been reported
➢ In most cases, only thyroid hormone administration is sufficient to ameliorate the
psychiatric symptoms, but when severe psychotropic medications may be used initially
as a symptomatic management
➢ In some cases, especially in severe deficiency and delay in treatment, cognitive
deficits, fatigue and psychological symptoms may persist, even after normalizing
thyroid levels
➢ Conversely, mood stabilizers such as lithium and carbamazepine are implicated in
causing hypothyroidism, simultaneously worsening the psychiatric symptoms

Hyperthyroidism and Psychiatric disorders:

➢ Commonly presents with features of anxiety, irritability, emotional lability and fatigue,
➢ Significant cognitive deficits maybe evident
➢ Further can progress into delirium or mania
➢ Less commonly, can develop a psychosis, with paranoid ideations or a depressive
picture with PM retardation, apathy and social withdrawal
➢ With regards to pharmacotherapy two important caveats are-
1. Cardiotoxicity and neurotoxicity – added effect of thyroxine onto TCA or MAOi’s
on cardiac states, and onto antipsychotic agents worsening neurological adverse
effects
2. Thyroid storm- antipsychotics, such as haloperidol, can precipitate or worsen
hyperthyroidism

Thyroid and ADHD:

➢ Thyroid receptor alterations can mimic symptoms of ADHD in animals

➢ Thyroxin resistance is associated with ADHD symptoms in humans

Thyroid auntoimmunity and Psychiatric disorders:

➢ Thyroid autoimmunity may play a role in some psychiatric illnesses

➢ Antithyroid antibodies are found more frequently in women with unipolar depression
and in both men and women with bipolar disorder
➢ It is associated with treatment resistance as well
➢ Thyroid antibodies are higher in fibromyalgia and rheumatoid arthritis

Mood stabilizers and HPT axis:

Lithium:
1. Increases antithyroid antibodies

437
 2. Inhibits iodine uptake and tyrosine iodination
3. Inhibits release of T3 and T4 from the thyroid
4. It also regulates TR gene expression
5. Blocks the thyroid-stimulating effects of TSH

➢ 30 percent of people receiving lithium have elevated TSH levels with 16% develop
frank hypothyroidism
➢ Even subtle alterations and subclinical changes need to be attended to as there is an
association of lower serum T4 and mood instability
➢ Also, hypothyroidism may be misdiagnosed as depression
➢ Carbamazepine also decreases peripheral thyroid hormone concentrations while
increasing TSH

Psychoneuroendocrinology

Dr Akshit Shetty
Dr Aparajita Arora

Psychoneuroendocrinology:

➢ It combines psychiatry, psychology, neurology, neurobiology, neurosciences and

endocrinology
➢ Typically, endocrine organs release hormones into the blood by an organ causing an
effect in areas distant from origin
➢ CNS:
o Serves as the site of regulation of hormonal release
o Has Hormonal secretory functions
o Serves as end organ for action of hormones- as an independent
neurotransmitter or a neuromodulator of other neurotransmitters
o Hence, the relationship between the anatomy and physiology of neurons and
that of endocrine cells remain inter-dependant
➢ There are two modes of action of hormones:
1. Genomic:
Responsible for late onset action, as it makes a genomic change by altering
transcription
E.g- Steroid hormones (glucocorticoids, estrogen, and testosterone)
Thyroid hormones (triiodothyronine [T3] and thyroxine [T4])
2. Non-genomic:
Leads to rapid response, within seconds to minutes, with usual site of action being the
cell membrane receptors
e.g estrogen-stimulated prolactin release

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 Typically, nongenomic mechanisms don’t get inhibited as opposed to genomic
mechanisms
Genomic and nongenomic mechanisms may be active simultaneously

Effect of Hormones on Development:

Various hormones play pivotal roles at specific points in development

Below are mentioned normal and pathological developmental processes

1. Gonadal hormones-changes in brain morphology and function & differentiation of

dopaminergic neurons
2. Thyroid hormones are essential for the normal development of the CNS, with
deficiency at critical periods leading to cretinism
3. Prenatal exposure in animals to endogenous or exogenous glucocorticoids or to
stressful circumstances may result in long-lasting immune and metabolic changes,
increased risk of attentional deficits, increased anxiety, and disturbed social behavior
4. Maternal deprivation in rats shows increased glucocorticoid response to stress. Also
as increase in anxiety, substance preference and difficulty learning in adulthood
5. Epigenetic mechanisms- lead to alteration in endocrine receptor genes and
subsequently behaviors can be learnt.

Psychoneuroendocrinology research in Humans:

Clinical Psychoneurendocrinology is a relatively young area of research

Most of the work in this area is limited to animal models, with human studies being restricted
to:
1. Absolute or relative measurements of concentrations of various hormones in different
body fluids, such as plasma, urine, saliva, CSF, or postmortem tissue
These measurements are correlated to either symptoms, disorders, neurotransmitter
action, or treatment response
2. Provocative tests such as the dexamethasone-CRH test, with former inhibiting and
the latter stimulating cortisol secretion. Though there is some evidence of abnormality
in this test found in bipolar disorder, major depression, schizophrenia, and PTSD, it
remains an unreliable diagnostic tool
3. Administration of hormones or secretagogues to correct an abnormal hormone
concentration leading to structural brain changes which are imaged and correlated to
cognitive and behavioral effects
4. Genetic polymorphisms in various endocrine receptors are shown to have significance
in:
• Possible future subtyping of disorders
• Treatment response and outcomes
• Mechanism of action of non-pharmacological mechanisms
5. Use of genetically engineered mice as animal models of disease by specifically
targeting genes related to hormones.

439
To summarize, Psychoendoneurological evaluation generally follows three paths:

1. Primary psychiatric illness with alterations in hormone levels

2. Primary endocrine illness with psychological symptoms

3. Psychiatric effects of exogenously administered hormones

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Basic Psychology

441
 Attachment theory and its implications

Dr Subbulakshmi Kota

Introduction:

➢ Attachment theory originated in the work of John Bowlby, a British psychoanalyst

➢ In his studies of infant attachment and separation, Bowlby pointed out that attachment
constituted a central motivational force and that mother and child attachment was an
essential medium of human interaction that had important consequences for later
development and personality functioning
➢ Being monotropic, infants tend to attach to one person; but they can form attachments
to several persons such as the father or a surrogate
➢ Attachment develops gradually; it results in an infant's wanting to be with a preferred
person, who is perceived as stronger, wiser, and able to reduce anxiety or distress
➢ Attachment thus gives infants feelings of security
➢ The process is facilitated by interaction between mother and infant; the amount of time
together is less important than the amount of activity between the two
Definition and theories of attachment:

➢ Attachment can be defined as the emotional tone between children and their
caregivers and is evidenced by an infant's seeking and clinging to the caregiving
person, usually the mother
➢ By their first month, infants usually have begun to show such behavior, which is
designed to promote proximity to the desired person
➢ The term bonding is sometimes used synonymously with attachment, but the two are
different phenomena. Bonding concerns the mother's feelings for her infant and differs
from attachment
➢ Mothers do not normally rely on their infants as a source of security, as is the case in
attachment behavior
➢ Much research reveals that the bonding of mother to infant occurs when there is skin-
to-skin contact between the two or when other types of contact, such as voice and eye
contact are made
➢ Some workers have concluded that a mother who has skin-to-skin contact with her
baby immediately after birth shows a stronger bonding pattern and may provide more
attentive care than a mother who does not have this experience
➢ Some researchers have even proposed a critical period immediately after birth, during
which such skin-to-skin contact must occur if bonding is to take place
➢ Alongside cognitive development, children are developing both socially and
emotionally. It has been recognized for years that children brought up in institutions,
away from their natural parents, often develop serious and subtle problems in social
interactions and emotional development.
➢ Arising in part from his studies of infants in institutions and his collaborative studies of
children's reactions to being in hospital, as well as his dissatisfaction with
contemporary psychoanalytic theory, Bowlby turned to ethology for an understanding

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 of early infant relationships. He came to view the intense relationship between the
infant and the caretaker, usually but not always the biological mother, as serving a
biological survival value and having been produced by natural selection.
➢ As memory develops in the first year of life, and as the infant becomes more able to
express emotion and to move independently, so there is evidence for selective
attachment. This is shown round about 6 to 8 months onwards by the upset at leaving
the attachment figure, by seeking his or her comfort when feeling threatened, and by
a general wariness of strangers.
➢ The idea that attachments were simply associative learning—the baby comes to love
the person who feeds him or her—was quickly dismissed by the evidence from
Harlow's studies of infant monkeys. They attached to the cuddly terry-towelling
surrogate rather than the wire surrogate where they were fed.
➢ Rather, selective attachments in the human served to protect the infant during the
prolonged period of helplessness. The function of attachment changes over the years,
with children using an attachment figure as a secure base from which to explore. Thus,
almost paradoxically, the well-attached toddler may move away from the attachment
figure more than the insecurely attached counterpart. Attachment is not the same as
clinginess.
➢ By the age of 3 to 4 years, most children show good evidence of having multiple
attachment figures. By this age, their memories are so much greater that they are less
dependent on the physical presence of the attachment figure to provide security and
comfort. Bowlby saw good attachments in infancy as laying the basis for future social
and intimate relationships and there is currently an explosion of work re-examining
psychiatric conditions from an ‘attachment perspective'.
➢ Thus, Bowlby saw the child as developing a cognitive model of his or her effective
social world, in keeping with the views of other cognitive theorists such as George
Kelly, Aaron Beck, and Ronnie Janoff-Bulmann.
➢ It needs to be emphasized that the pattern of attachment characterizes a particular
dyadic relationship and children can show different types of attachment to different
caretakers
➢ Even so, the characterization of such attachment behaviour in the 12- to 18-month
period has been shown to predict reasonably to patterns of social behaviour 4 years
later.
➢ A negative aspect of the focus on attachments has been the emergence of an ill-
defined disorder described as ‘reactive attachment disorder' which seems to be
diagnosable by the presence of any or all of a long list of symptoms and signs that
haunted previous generations under such labels as minimal brain dysfunction and the
like
➢ This has been associated in some countries with the use of assaultative ‘holding
therapies' intended to break the child's resistance to forming attachments. Clearly,
more careful studies need to be undertaken to try to pinpoint the subtle social
difficulties presented by children whose early lives have been disrupted as in fostering
and adoption but care also needs to be taken to adduce evidence for appropriate
interventions.

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Ainsworth and types of attachments:

➢ Ainsworth et al. developed the theory and a method for detecting individual differences
in attachment
➢ They introduced the ‘strange situation' test in which an infant is left in the care of a
stranger for a few minutes
➢ The observer then notes how the infant copes both with the separation and with the
reunion with the attachment figure
➢ These observations led to a tripartite classification of attachments
1.Secure attachment:

➢ The infant tends to seek proximity and contact with the attachment figure, shows a
preference for the attachment figure over a stranger, and shows very little distress
before and after separation
➢ Any distress is easily soothed by the comfort of the attachment figure
2.Avoidant insecure:

➢ The baby does not cling when held, avoids the mother (or caretaker) during the
reunion, and does not differentiate greatly between the caretaker and a stranger
3.Resistant insecurity:

➢ The infant resists contact and interaction with the mother

➢ There is great distress at reunion
4.Disorganized or avoidant insecurity:

➢ This category had to be introduced when it was found that infants of severely
depressed and abusive mothers showed a mixed pattern of attachments
➢ The child shows contradictory patterns and unusual patterns of negative emotions
Implications of attachment in Psychiatric disorders:

➢ Having good supportive social relationships has been shown to be a major protective
factor in the aetiology and maintenance of many psychiatric disorders
➢ The ability to make and maintain friends—initially of the same age and later of any
age—is often related to the existence of disorders such as personality disorders, social
anxiety disorders, depression, and even PTSD
➢ The emphasis on social skills training for socially inadequate persons points to the
early basis for such deficits even though they may have their greatest impact in
adulthood
➢ Some children are less sensitive to social cues than others, and some misinterpret the
intentions of other people. Both lead to difficulties, albeit of different sorts
➢ Boys and girls tend to develop different types of social relationships
➢ Children tend to prefer playing with others of the same gender when freed from adult
influence
➢ Boys tend to play in larger, looser groups in which issues of dominance and play
fighting predominate; girls relate in smaller groups of more intense relationships, with
best friends often changing.
➢ Young children show an interest in each other from a very early age:
• 2 months—infants will orient to other babies

• 3 months—will reach out and try to touch other babies

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 • 6 months—additionally will smile and vocalize to the other baby

• 6 to 12 months—increase in attempted interactions, but low rate of response

• 12 to 24 months—more varied interactions, with negative ones increasing.

➢ Altruism and empathy are present in normal children from early on with positive
interactions increasing. But competitiveness and rivalry also increase in the preschool
years

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 Discuss The Psychological And Biological Theories Of Hallucinations

Dr Subbulakshmi Kota

Introduction:

➢ Esquirol defined hallucinations as perceptions without an object

➢ Jaspers defined hallucinations as false perceptions which are not sensory distortions or
misinterpretations, but which occur at the same time as real perceptions
Theories of hallucinations:

1. Psychological theories:

a) Psychodynamic theories:

➢ Freud - Similarity with dreams

➢ In this process, thoughts are transformed into visual images, mainly of a visual sort,
that is, word presentations are taken back to corresponding “thing” presentations
b) Kolb and Brodie:

➢ Breakthrough of preconscious or unconscious material into consciousness in

response to certain psychological situations and needs, e.g., wish fulfillment,
enhancement of self-esteem, guilt feelings
➢ The contents of hallucinations are thought to reflect their psychodynamic
significance
➢ May represent the concrete symbolic expression of delusional ideas that are seeking
other routes of expression.
2. Cognitive perceptual theories:

➢ Hallucinations can be seen as erroneous perception or “sensory deception.”

➢ Hence researchers have been investigating the integrity of perceptual functions in persons
with hallucinations
➢ 2 approaches:
Bottom-up or data-driven approach:

1. Deficits in the processing of incoming stimuli in primary cortex

2. Hearing impairment and auditory hallucinations associated with sensory impairment in older
people
3. The emergence of hallucinations in sensory deprivation

Top-down or conceptual approach:

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 1. Processes that contribute to perception that do not originate in the external world but in the
brain of the perceiver
2. Examples of such top-down factors are prior knowledge, perceptual expectations,
attentional modulation and mental imagery
❖ Deficits in source monitoring:
➢ Bentall (1990) proposed that discrimination between internal and external sources of
information is a metacognitive skill called source monitoring
➢ Hallucinations result from failure of this skill
❖ Parasitic memories:
1. Hoffman et al. (1994) proposed hallucinations are due to disruption in language production
caused by parasitic memory
2. Disconnection of areas leads to few areas functioning autonomously without external stimuli
3. Language production processes are disrupted by parasitic memories. These memories
intrude unintended into awareness, producing verbal imagery that is experienced as alien to
the self.
❖ Inner speech:
➢ David (1994) linked verbal hallucinations to inner speech. He argued that inner speech is
produced and controlled by an inner-voice-inner-ear system, and the disruption of the
system may lead to verbal hallucinations.

❖ Hamsley proposed emergence of long-term memories into awareness as hallucinations.

❖ This is because of weakened influence of past memories in perception leading to ambiguous
and unstructured sensory input
3. Biological theories:

Aetiological theories are of three kinds:

1 Overstimulation affecting different levels of information processing

2 Failure of inhibition of mental functions

3 Distortion of the processing of sensory information at the interpretive level

➢ The work of Penfield and Perot has suggested that overstimulation may be a pathogenetic
mechanism
➢ They stimulated the temporal regions of 500 patients, of whom 8 per cent reported scenic
hallucinations, some in several modalities
➢ Stimulation of the visual occipital cortex led to simple hallucinations like flashes, circles,
stars, or lines. This phenomenon, known as Formkonstanz, has been observed in drug-
induced experimental psychosis, which is the most obvious overstimulation paradigm
➢ It is interesting that schizophrenic patients can usually distinguish drug-induced
hallucinations from those arising from their disorder
➢ Using neural network theories, Hoffmann simulated hallucinations by using Hopfield
networks; overloading the storage capacity of the network generated what can be
considered as the equivalent of hallucinations
➢ The disinhibition theory originated with Hughlings Jackson, who considered that positive
symptoms were caused by the disinhibition of controlling neural activities, while negative
symptoms resulted from damage to the systems which generate the positive symptoms
➢ A modern approach to disinhibition theory is sensory deprivation research using dark and
sound-proofed environments, but this has yielded inconsistent results

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 ➢ Hallucinations, narrowly defined, seldom occur after deprivation, which may be of greater
relevance to the vivid, usually visual, imaginative experiences by certain people described by
Galton in 1880, and later by Jaensch, as ‘eidetic types'
➢ Disinhibition may also underlie the ‘hypnagogic hallucinations' which can occur in healthy
persons shortly before they fall asleep
➢ The role in the production of hallucinations of the postsensory interpretation and evaluation
of stimuli is uncertain
➢ In these terms hallucinations are a sort of deception, but this is not a sufficient description of
their nature
➢ Recent neurophysiological hypotheses and findings from neuroimaging studies have
suggested that there is an ‘inner censorship' which deals with the ambiguities of perceptions
by setting hierarchies of contingencies.
4. Perception and attention deficit model

➢ Collerton et al. (2005) proposed a PAD model of complex visual hallucination, in which the
hallucinatory images generally occur in the focus of the visual field and are seen against the
background of the existing visual scene
➢ According to the PAD model, both sensory impairment and attentional abnormalities are
needed for hallucinations to arise
➢ More specifically, a combination of impaired attentional binding and poor sensory activation
of a correct proto-object, in conjunction with a relatively intact scene representation, biases
perception to allow the intrusion of a hallucinatory proto-object into a scene perception
➢ Proto-objects refer to holistic or part-based abstracted object representations that are
segmented from visual information and act as candidates for further processing but are at
such an early processing stage that they have not yet entered conscious awareness
➢ Such proto-objects are in multiple competitions for further processing
➢ The interplay of top-down and bottom-up biasing information will eventually determine
which proto-object will “win” and enter conscious awareness
➢ Cholinergic dysfunction may result in a failure to properly integrate sensory information
(bottom-up) and prior expectation (top-down)
➢ The PAD model proposes that impaired attentional binding is due to abnormal lateral frontal
activity; poor sensory activation of a correct proto-object is due to abnormal ventral visual
stream activity; and intrusion of a hallucinatory proto-object is mediated by increased
temporal versus frontal activity
➢ Diederich et al. (2005) suggested that visual hallucinations should be considered a
dysregulation of the gating and filtering of external perception and internal image
production
➢ Contributive factors for their model include poor primary vision, reduced activation of
primary visual cortex, aberrant activation of associative visual and frontal cortex, lack of
suppression or spontaneous emergence of internally generated imagery through the ponto-
geniculo-occipital system, intrusion of rapid eye movement dreaming imagery into
wakefulness, erratic changes of the brainstem filtering capacities through fluctuating
vigilance and medication-related overactivation of mesolimbic system
➢ Not all of these have to be present, and different combinations will lead to differences in
phenomenology
➢ Llinas and Pare (1991) suggested that conscious perception is subserved by intrinsic activity
in thalamocortical circuits that is constrained or modulated by sensory input. They
considered the primary difference between conscious perception and dream imagery to be

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 found in the weight given to sensory input, which is a large weight in conscious perception,
and hence sensory factors largely determine the final percept, whereas this weight is
negligible in dream imagery
➢ Integrating the sensory impairment approach with the top-down approach, Behrendt and
Young (2004) viewed hallucinations as “underconstrained perceptions” that arise when the
impact of sensory input on thalamocortical circuits is reduced
➢ If sensory constraints (i.e., bottom-up processing of incoming information) are weak, e.g.,
due to sensory impairment, attentional mechanisms (i.e. top-down influences) may become
the dominant modulatory influence on thalamo-cortical oscillatory activity that gives rise to
conscious percepts — in this case, hallucinations.
5. Neural network model:

➢ To test different hypotheses regarding neurocognitive basis of hallucination, Hoffman and

McGlasher (2006) developed a neural network simulation
➢ Their model specifically concerns auditory hallucinations as typically reported in people with
schizophrenia and is based on 2 popular hypotheses regarding neurobiological basis of
schizophrenia:
o Overzealous pruning of synapses that are an extension of normal developmental
pruning during adolescence
o Alterations in the dopaminergic neuromodulatory system in schizophrenia
➢ To assess and compare these 2 hypotheses, a computer simulation of some aspects of
speech perception was developed
➢ This system was found to produce spontaneous percepts simulating hallucinated speech
when the working memory component was excessively pruned or when neuronal responses
were modulated to simulate a hyperdopaminergic system
➢ Comparing the performance of the network with that of actual hallucinating patients and
normal controls while tracking (repeating while simultaneously listening to) speech that was
phonetically degraded, revealed that the neural network simulation producing the best
match to speech-tracking performance of human hallucinators was an overpruned system
with compensatory hypodopaminergic adjustments
6. Metacognitive process:

➢ Reality monitoring and metacognitive beliefs

➢ Metacognition refers to “thinking about thinking” or to beliefs and attitudes held about
cognition
➢ Most recent models of hallucinations assume that hallucinations are related to
misattribution of private events
➢ These private events may include a number of types and modalities, such as inner images,
inner speech, voices, intrusive thoughts, vivid daydreams and bodily sensations
➢ Different approaches have attempted to explain this misattribution, with the most
prominent of these relating hallucinations to a misattribution of inner speech, problems in
source monitoring, and relations between hallucinations and beliefs
➢ Recent cognitive models of hallucination have attributed these misattributions to cognitive
bias or cognitive deficit
➢ Cognitive biases are present when some forms of information are processed preferentially in
comparison to others. Examples of cognitive bias include the preferential recall of negative
information in patients with depression
➢ Cognitive deficits occur when there are disruptions of specific cognitive functions, including,
for example, problems with working memory, inhibition or attention

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 ➢ It is probable that disturbances in cognitive processes as a result of cognitive deficits (i.e.,
bottom-up factors) and cognitive bias factors (top-down factors) are both responsible for
hallucinations

7. Reality monitoring and hallucinations – Bentall’s (1990) hallucination model

➢ Some studies provide evidence for Bentall’s notion that hallucinators are impaired in their
ability to discriminate between real and imagined events and reveal a specific bias towards
attributing their thoughts to an external source
➢ This externalizing bias seems related, at least in part, to the effects of both an inadequate
use of cognitive effort cues and the emotional salience of stimuli (Laroi et al., 2004) on
source-monitoring tasks

8. Hallucinations and beliefs – Morrison’ hallucination model

➢ Morrison - Hallucinations are internal cognitive events that are misattributed to an external
source
➢ Normal intrusive thoughts misattributed as hallucinations because of motivational factors
➢ Genesis of hallucinations is seen as a reaction to intrusive experiences which are egodystonic
➢ The theory also states that the need to attribute intrusive thoughts to an external source is
due to motivational factors
➢ The presence of certain intrusive thoughts may lead to negative affect in the subject in the
form of anxiety or cognitive dissonance
➢ According to cognitive dissonance theory, dissonance occurs when 2 cognitions (e.g.,
thoughts, beliefs and feelings the person is aware of) contradict each other, resulting in an
uncomfortable state from which an individual is motivated to escape
➢ Morrison et al. (1995) argued that to reduce the levels of negative affect, the subject
chooses to externalize the intrusive thought, resulting in hallucinations
➢ Morrison also posited the important role that metacognitive beliefs may play in this
misattribution process
➢ Metacognitive beliefs are beliefs concerning one’s own mental process. This may include
beliefs that mental events should be controllable, that thoughts are dangerous or harmful or
that intrusive thoughts are acceptable and beneficial
➢ When the occurrence of intrusive thoughts does not comply with the subject’s
metacognitive beliefs, an aversive state of arousal results (cognitive dissonance), which the
subject tries to escape by externalizing the intrusive thoughts (resulting in hallucinations),
thus maintaining consistency in his belief system. A number of studies have found evidence
for an association between metacognitive beliefs and the presence of hallucinations.

A comprehensive cognitive model of hallucinations:

Alemon and Laroi (2008) presumed that an integrated network of cognitive processes may
contribute to perceptual experience, and proposed that 4 different routes may result in a
hallucination:

1. Release phenomena due to lesions in sensory pathways/the arousal system (brainstem,

thalamus)
2. Irritative processes acting on cortical centers that integrate perceptual information

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3. Unconstrained activation of the attentional spotlight
4. A cognitive route with key roles for affective state, top-down factors and source-/self-
monitoring

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 Psychoanalytical theories of personality development

Dr Subbulakshmi. kota

Psychoanalytical theories central concern with dynamic forces that determine our behavior
and with the defensive structures one unknowingly erect to shield from those factors

Different psychodynamic theories

SIGMUND FREUD

Freuds theory-conflict model of motivation-behavior is driven by unconscious, biologically

based urges that demand gratification.

Structure of personality:
The Id:
➢ The original system of personality
➢ Matrix within which the superego and ego become differentiated
➢ The id consists of everything psychological that is inherited at birth including the
instincts
➢ Id is the true psychic reality and cannot tolerate any increase of energy that is
experienced during uncomfortable states of tension
➢ Thus it works in a manner as to discharge the tension immediately and return to
comfortable constant level
➢ Id operates on pleasure principle-whether the experience is pleasurable or painful
➢ It uses 2 processes-Reflex actions and primary processes

The ego:
➢ Ego comes into existence as the needs of organism require transaction with real
objective world
➢ The difference between id and ego is that id only knows the subjective reality whereas
ego can distinguish between subjective and objective reality
➢ Ego works on reality principle that is, whether the experience is true or false;whether
it has existence in reality or not
➢ It operates by using secondary processes
➢ Ego is called the executive of personality, it tries to integrate the conflicts of id,
superego and external reality

The Superego:
➢ Third and last system of personality to develop
➢ It is internal representation of traditional values and ideals of personality
➢ It is the moral arm of personality
➢ It develops in response to rewards and punishments imposed by parents.
➢ Two subsystems:
1. Approval and rewards-stored as ego ideal
2. Punishment stored in conscience - incorporated through process of introjection

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 ➢ It strives for perfection

• Freud stressed the decisive role of early years of life in the development of personality
• By the end of 5 yrs it is well formed and expands on the basic structure after that

➢ Personality develops through 4 major sources of tension:

1.Physiological growth process
2.Frustrations
3.Conflicts
4.Threats

Stages of development:
Stages are defined on the basis of mode of reaction of a particular zone of body

ORAL STAGE (Birth-1 year of life):

➢ Mouth is the zone of dynamic activity
➢ Mouth, tongue & lips – sources of sensual gratification
➢ Feelings of dependency arise during this period
➢ Resolution- capacities to give to & receive from others without excessive dependence
or envy & to trust on others
➢ Sense of self-reliance & self-trust
➢ Fixation- excessive optimism, narcissism, pessimism, dependence, envy & jealousy

ANAL STAGE ( 1-3 YRS):

Prompted by maturation of neuromuscular control of anal sphincters
When toilet training is initiated child has its first decisive experience with external regulation of
instinctual impulses
Resolution- personal autonomy, capacity for independence , creativity& lack of ambivalence
Fixation :
1. Expulsive traits- cruelty, temper tantrums, destructiveness
2. Retention traits-obstinacy, orderliness, stubbornness

PHALLIC STAGE (3-5 YRS):

Primary focus of sexual interests, stimulation & excitation is the genital area.

Oedipus complex:
➢ Sexual cathexis for the parent of the opposite sex and hostile cathexis for the parent
of same sex
➢ Attitude towards the opposite sex and people in authority is determined by this phase
➢ In case of male the complex leads to castration anxiety and induces repression of this
incestuous feeling and identification with father’s personality
➢ This leads to vicarious satisfaction in the child
➢ Penis envy is the female counterpart of castration anxiety, development of cathexis for
father
➢ Oedipus complex is modified but not strongly repressed as in the case of male child.

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Resolution:
➢ Sense of sexual identity & curiosity without embarrassment, sense of mastery not only
over objects & persons in the environment but also over internal processes & impulses
➢ Fixation at this stage leads to personality organised around oedipal fantasies and
proneness to regression to anal or oral organisation

LATENCY STAGE (5-6 TO 11-13 YRS)

Relatively quiescent in inactivity of sexual drive
Resolution-
➢ Integration and consolidation of previous attainments in psychosexual development,
establishing decisive patterns of adaptive functioning
➢ Mature adult life of satisfaction in work & love
➢ Fixation-failure to sublimate energies in the learning & development of skills due to
lack of control
➢ Excess of inner control leads to premature closure of personality development &
precocious elaboration of obsessive traits

GENITAL STAGE (11-13 TO ADULTHOOD )

➢ Maturation of genital & associated hormonal systems – sense of self love and
narcissism till this stage is now channeled to objective world. Cathexis of all prior
stages is diffused into genital stage
➢ Resolution – mature personality, sense of self-identity & self-realization, meaningful
participation in work, love, creative & productive activities
➢ Fixation – defects in the emerging adult personality, identity diffusion
➢ Freud also gave topographical division of mind into 3 regions or systems as defined
by their relationship to conscious thought: the conscious; the preconscious and the
unconscious

CONTRIBUTIONS BY NEO-FREUDIANS TO PERSONALITY DEVELOPMENT:

CARL JUNG:
Jung rejected the over emphasis on infantile sexuality
Gave the terms:
1. Personal unconscious which harbors complexes
2. Collective unconscious which has archetypes
Persona:
1. Our public self, the front a person puts on to other people
2. The mask that makes the person and others believe that he/she is an individual, when
he/she is actually acting a role through which the collective unconscious speaks
Shadow:
Represents the repressed, unconscious drives & desires of the personal unconscious, the
“dark side” of all humans
Anima -internalised feminine image in men
Animus- representation of masculinity in women
Jung's theory of psychological types has three axes:
1. The extroversion–introversion polarity refers to the two basic types of object
relatedness
2. The sensation–intuition polarity concerns perception
3. The thinking–feeling polarity deals with information processing and judgment

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Everyone has a preferred side in each dimension

ALFRED ADLER:
➢ Core of personality is inherent inferiority rather than instincts and repressed drives
➢ Adlers theories constitute individual psychology
➢ In Adler’s view, healthy people are motivated by goals related to others, while neurotic
personalities are self-centered
➢ According to Adler, Oedipus complex shows a need to be better than the father
➢ Inferiority Complex:
o A sense of inadequacy that in universal and inborn
o Fixation on feelings of personal inferiority can lead to emotional and social
paralysis
➢ Adler also proposed parenting styles and the significance of birth order in one’s
personality

ERIC ERIKSON:
Gave psychosocial stages of development
The Erikson life-stage virtues, in the order of the stages in which they may be acquired, are:
1. Hope - Basic Trust vs. Mistrust - Infant stage / 0-1 year
2. Will - Autonomy vs. Shame and Doubt - Toddler stage / 1–3 years
3. Purpose - Initiative vs. Guilt - Preschool / 3–6 years
4. Competence - Industry vs. Inferiority - School-age / 6-11
5. Fidelity - Identity vs. Role Confusion - Adolescent / 12 years till 20
6. Intimacy vs. Isolation- 20 to 24 years
7. Generativity vs. Stagnation (25 to 64 years) is the second stage of adulthood and
happens between the ages of 25-64
8. Ego integrity vs. Despair (>65 years)

KAREN HORNEY:
➢ Horney believed that a person's current personality attributes result from the interaction
between the person and the environment and are not solely based on infantile libidinal
energy carried over from childhood
➢ Theories contribute to Holistic psychology:
➢ person needs to be seen as a unitary whole who influences and is influenced by the
environment
➢ Gave the term womb envy
➢ Basic Anxiety- Anxiety created when a child is born into the bigger and more powerful
world of older children and adults
➢ Children who receive love, affection, and security from their world overcome the
anxiety
➢ Those who grow up in a world with less security and love develop neurotic personalities
➢ 3 Character Types
1. Compliant, self-effacing type
2. Aggressive, expansive type
3. Detached, resigned type
➢ 3 concepts of self:
1. Real self
2. Ideal self

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 3. Actual self

HARRY STACK SULLIVAN:

Self-system of development:
1. INFANCY- anxiety when primary needs are not satisfied
2. CHILDHOOD- learn culture, dealing with adults
3. JUVENILE- need for peers, dealing with them
4. PREADOLESCENCE- capacity for love and collaboration with peer group (same sex)-
chum period
5. ADOLESCENCE- separation from family, standards and values, heterosexuality

MALANIE KLEIN
➢ Object relations theory
➢ Object refers to mental representation of any person or part of a person
➢ Kleins emphasis was on Interpersonal relationships
➢ Intimacy and nurturance from mother
➢ Human contact as a motivating factor
➢ She modified Frueds theory of psychological development
➢ During the 1st year of development she described 2 psychological positions
1. Paranoid schizoid position -6months
o Projection of death instinct onto mother leading to persecutory anxiety
o Infant organizes the experiences and splits them into good and bad
elements
2. Depressive position-6months to 1yr
o Develops the understanding that good and bad elements are part of the
same complex object and fears harm
o Here the mother is perceived ambivalently with feelings of both love and
hate

DONALD W WINNICOTT:
➢ Gave multiple self-theory
➢ True self and False self
➢ He also gave the term transitional objects

WILHELM REICH:
➢ Postulated different character types
➢ The term character armor refers to the personality's defenses that serve as resistance
to self-understanding and change
➢ The four major character types are as follows:
1. Hysterical
2. Narcissistic
3. Compulsive
4. Masochistic

ERICH FROMM:
Fromm identified five-character types that are common to, and determined by, Western
culture; Each person may possess qualities from one or more types
The types are:

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1. Receptive personality is passive
2. Exploitative personality is manipulative
3. Marketing personality is opportunistic and changeable
4. Hoarding personality saves and stores
5. Productive personality is mature and enjoys love and work

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 Self-Actualization theory-Contribution in understanding the
human development/ Maslows hierarchy of needs

Dr Subbulakshmi Kota

Introduction:
➢ Concept of self and self-actualization is emphasized in humanistic theories/organismic
theory
➢ Individual is motivated by one sovereign drive that is called by Kurt Goldstein as self-
actualization or self-realization
➢ Humans always strive to this goal

Concepts of organismic theories:

1. Organization is the natural state of personality; disorganization is pathological and
brought about by oppressive and threatening environment
2. Organism as a system analyses the constituent members
3. Organism minimises the primary and directive influence of environment but focuses on
the inherent potentialities of organism
4. Comprehensive study of a single individual is important than the study of individual
psychological function or traits.

➢ According to Goldstein all the drives like hunger, sex, power, achievement and
curiosity are different manifestations of the master motive; to actualize oneself
➢ Self-actualization is the creative trend of human nature
➢ Any need is a deficit state that motivates the person to replenish it
➢ Self-actualization is a universal phenomenon, the specific ends vary from person to
person

Abraham Harold Maslow:

➢ He proposed a holistic dynamic point of view that has a lot of similarities with
Goldstein’s theory
➢ Maslow proposed a theory of human motivation based on a hierarchy of needs
➢ In the hierarchy the lower the need the more dominant it is,so when several needs are
active the lowest is the most compelling
➢ Needs include both deficiency needs and growth needs
➢ Needs at lower level are triggered by deficit while those at higher level are entailed by
growth motivation that is for personal growth
➢ Self-actualization is the point seldom reached at when people have satisfied the lower
needs and achieved their full human potential
➢ Maslow proposed that there are several levels of needs that a person must strive to
achieve before achieving the highest level of personality fulfillment
➢ Originally Maslow included only five stages
➢ Later he added cognitive needs, aesthetic needs and transcendence needs

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 ➢ People go up pyramid as they go through life gaining wisdom and knowledge on how
to handle many different situations
➢ A shift in a life’s circumstances can lead down to a lower need

I. Physiological needs:
Hunger, thirst, sex and other somatic drives
These are preemptive and dominate, they push all other needs to background
II. Safety needs:
Security, stability, protection, dependency
More obvious in infants
III. Belongingness and love needs:
Need for friends, family and affectionate relationships
IV. Esteem needs:
Self-esteem- strength, achievement, mastery and competence
Esteem from others- desire for fame, dominance, status, attention, dignity
V. Self-actualization:
The desire to become more and more, to become everything one is capable of becoming

Peak experiences-
Times in a person’s life during which self-actualization is achieved at least temporarily

Study of self-actualizers:

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 ➢ Maslow studied mentally healthy individuals instead of people with serious
psychological issues. He studied a group of self-actualizers from history like Lincoln,
Beethoven, Thoreau and people living at his time like Roosevelt, Einstein
➢ This informed his theory that people experience “peak experiences", high points in life
when the individual is in harmony with himself and his surroundings
➢ In Maslow's view, self-actualized people can have many peak experiences throughout
a day while others have those experiences less frequently
➢ Maslow noticed that self-actualized individuals had distinct characters like a better
insight of reality, deeply accepted one-self, others and the world, and also had faced
many problems.
➢ These self-actualized individuals were very independent and private when it came to
their environment and culture, especially their very own individual development on
potentialities and inner resources

Carl Rogers:
➢ He stated that the organism has one basic tendency and striving-to actualize, maintain
and enhance the experiencing organism
➢ Single motivating force is self-actualizing drive and the goal is to become a whole or
self-actualized person
➢ The organism actualizes itself along the lines laid down by heredity
➢ It becomes more differentiated, more expanded, more autonomous and more
socialized as it matures

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 What is Social cognition? How is it measured? What is its
implication to psychiatry?

Dr Subbulakshmi Kota

Introduction:

➢ The social cognition construct provides a broad perspective that focuses on how
people process information within social contexts
➢ The term social cognition is defined in various ways:
➢ Adolphs defined social cognition as ‘‘the ability to construct representations of the
relation between oneself and others and to use those representations flexibly to guide
social behavior.’’
➢ It generally refers to the mental operations that underlie social interactions, including
perceiving, interpreting, and generating responses to the intentions, dispositions, and
behaviors of others
➢ Social cognition means people thinking and forming impressions about people
➢ Social cognition may impact the functional outcome of independent living skills
because accurately assessing social cues from the environment and having the social
opportunities necessary to learn skills, may be a necessary prerequisite for making
improvements in daily living skills.
➢ Social cognition is a broad construct encompassing many abilities.
The ones identified and studied are emotion perception (EP), social perception (SP), theory
of mind (ToM), and attributional style (AS).

1.Theory of mind:

➢ The term theory of mind (ToM) refers to the cognitive capacity to represent one's own
and other persons' mental states, for instance, in terms of thinking, believing, or
pretending
➢ Much of initial interest in this area focused on studies of children and how theory of
mind is acquired in normal and abnormal development
➢ Hence, many measures in this area were initially developed for use with children
➢ Theory of mind has been extended to schizophrenia, partly due to similarity between
aspects of social dysfunction in autism and a subgroup of patients with schizophrenia,
and following suggestions that abnormalities in this process can account for the
formation of clinical symptoms
2. Social perception:

➢ Tests of social perception assess one’s ability to identify social roles, societal rules,
and social context
➢ In social perception tasks, participants must process nonverbal, paraverbal, and/or
verbal cues to make inferences about complex or ambiguous social situations

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 ➢ Individuals may be asked to identify interpersonal features in a situation such as
intimacy, status, mood state, and veracity
3. Social knowledge:

➢ This area refers to awareness of the roles, rules, and goals that characterize social
situations and guide social interactions
➢ Social knowledge (also called social schema) can be measured with paper and pencil
tests that assess one’s awareness of what is socially expected in different situations
(eg, in a doctor’s office vs in a restaurant).
➢ It has been studied somewhat less than the other areas in schizophrenia, and it
overlaps with social perception; successful social knowledge requires awareness of
which cues occur typically in specific social situations (ie, social perception) and how
one is supposed to respond to them
➢ Social knowledge is viewed as an initial step and prerequisite for adequate social
competence and has been targeted for intervention in some social skills training
programs for schizophrenia
4. Attributional bias:

➢ Attributions are causal statements; ie, statements that either include or imply the word
‘‘because.’’
➢ Unlike mental state attribution (theory of mind), attribution bias or style reflects how
people typically infer the causes of particular positive and negative events
➢ Attributions can be measured by questionnaires or rated from transcripts of
interactions
5. Emotional processing:

➢ Emotional processing refers broadly to perceiving and using emotions

➢ One influential model of emotional processing defines emotional intelligence as a set
of 4 components, including identifying emotions, facilitating emotions, understanding
emotions, and managing emotions.

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 Social theories of schizophrenia and it’s clinical relevance

Dr Subbulakshmi Kota

Introduction:
➢ Different types of genetic, biochemical, physiological, psychological and social theories
have been postulated for schizophrenia.
➢ Different sociological factors were taken into consideration while understanding the
onset and progression of schizophrenia:
1. Family theories
2. Life events
3. Socio cultural factors
4. Stress Diathesis model

A. FAMILY THEORIES:

1) PARENTING AND COMMUNICATION:

Studies of interactions in families having schizophrenic offspring have focused on
factors like schizophrenogenic parents, destructive parental interactions and faulty
communication.

a) Schizophrenogenic Mother:
The term was propounded by Fromm Reichmann (1948)
Schizophrenogenic mother is found to be cold, rejecting and controlling

b) Double Bind Communication:

➢ Gregory Bateson (1959, 1960) was one of the first investigators to emphasize
the conflicting and confusing nature of a communications among members of
families experiencing a schizophrenic outcome
➢ Communication theory of schizophrenia discusses the relationship between
family homeostasis and schizophrenia
➢ Schizophrenia as the result of the way the schizophrenic’s family interacts
➢ In the double bind pattern the parent presents to the child ideas, feelings and
demands that are mutually incompatible. For eg, a mother may be verbally
loving and accepting but emotionally anxious and rejecting; or she may
complain about her sons lack of affection but freeze up or punish him when he
approaches her affectionately
➢ The mother subtly but effectively prohibits comments on such paradoxes, and
the father is too ineffectual or distanced to intervene. Hence the son is
continually placed in situations where he cannot win & thus becomes
increasingly anxious
➢ Once the individual has learnt to perceive his universe in ‘double bind patterns’
this complete set of conditions may not be needed to and part of it may be
enough to cause panic or rage

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 ➢ The elements of the double bind are:
❖ The presence of two persons
❖ Often repeated experiences
❖ A ‘primary negative injunction’ to do, or not to do, something with a threat
of punishment if the order is not obeyed
❖ A secondary injunction’ which conflicts with the first at a more abstract level,
often communicated non-verbally, again with threats of punishment
❖ A situation from which the ‘victim’ cannot escape
❖ Presumably such disorganized and contradictory communication in the
family come to be reflected in his own thinking

2) PSEUDO MUTUALITY & PSEUDO HOSTILITY:

As per Wyne et.al two fundamental needs of human beings are:

(1) To establish relationships with each other
(2) To develop, in a lifelong process, a sense of identity

They spoke about peculiar patterns of relatedness in the family

Pseudo – mutuality:
➢ It is based upon a felt need by the individual for a relationship
➢ It is felt perhaps because of failure in other relationships or, in a child, because of
painful earlier experiences of separation anxiety
➢ This leads to an attempt by each person to maintain the idea or feeling that his or her
behavior & expectations meet the needs of other person
➢ Thus those involved in a pseudo – mutual relationship are predominantly concerned
with fitting together at the expense of their respective identities
➢ Pseudo- mutual relationship tends to get into difficulties when there is growth in one
member, or a changed situation
➢ This may lead to the non-fulfillment of expectations & perhaps also the assertion of a
member’s personal identity
➢ The pseudo- mutual relationship may not be able to adapt to such changes, with
resulting tensions or even breakdown of the relationship
➢ The basic dilemma of a pseudo – mutual relationship is thus that divergence is seen
as leading to disruption of the relationship & so must be avoided; but this avoidance
makes growth of the relationship impossible

Pseudo-hostility:
➢ The apparent emotional relationship, in this case hostility rather than mutuality, is a
surface phenomenon only
➢ A true, intimate relationship is absent and as a substitute there is pretence at one.
An alignment is ‘the perception or experience of two or more persons that they are

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 joined together in a common endeavor, interest, attitude or set of values & that in this
sector of their experience they have positive feelings toward one another’.
➢ A split is ‘a comparable perception or experience of opposition, difference or
estrangement, with associated negative feeling.’

❖ Pseudo – mutuality & Pseudo – hostility are seen as ‘self-rescuing operations’

❖ Pseudo – mutuality is a surface alignment which obscures & prevents the recognition
of underlying splits & divergence
❖ Those involved act as if the underlying unsettled business has been resolved; it has
not however, & the existence of the surface alignment makes it difficult for resolution
to occur
❖ The Pseudo – hostility is similarly a ‘surface phenomenon’. It is a split or alienation,
which may be exceedingly noisy & intense but remains limited to a surface level of
experience & interaction’
❖ Pseudo – hostility can obscure & cover over anxiety – producing intimacy and affection,
or ‘deepening hostility’- hostility which might otherwise lead to destructive behavior,
openly acknowledged helplessness & lasting separation.

3) SCHISM & SKEW:

➢ The family process of schism and skew also figured prominently in early family
approaches to schizophrenia
➢ These are terms introduced by Theodore Lidz & his co-workers at Yale University
➢ These workers studied sixty schizophrenic families intensively
➢ Lidz and his co-workers judged all the families of schizophrenics that they studied to
be seriously disturbed & they found that either Schism or skew was present in
everyone
➢ Schism is the division of the family into two antagonistic & competing groups
➢ This pattern of family interaction entertained to undermine the standing of the others
in the eyes of the child
➢ Lidz et al highlighted the ineffectiveness, insecurity and paranoia among the parents
that drove this family process
➢ Skew exists where one partner in the marriage dominates the family to a striking
degree, as a result of serious personality disturbance in at least one of the partners

4) COMMUNICATION DEVIANCE:
➢ It refers to these deficiencies of precision and coherence leading to negative effects
parents have on their preschizophrenic children.
➢ Singer and Wynne linked the thought disorders in schizophrenia to 2 styles of thinking
and communication in the family.
Amorous pattern:
➢ Characterized by a failure in differentiation; here attention toward feelings, objects or
people is loosely organized, vague, and drifting
Fragmented thinking:
➢ Involves greater differentiation but lowered integration, with erratic & disruptive shifts
in communication

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 ➢ High parental communication deviance, measured during their children’s adolescence,
did indeed predict the occurrence of adult schizophrenic spectrum disorders among
offsprings.
➢ Finnish Adoption Study (Tienari, 1994): (Adoptive) parent communication deviance
was associated with the development of serious psychopathology in adoptees

5) EXPRSSED EMOTIONS:
➢ High EE was found to be in the best predictors for onset and relapse of schizophrenia
➢ The main dimensions are critical comments, hostility and emotional over involvement

6) LEARNING THEORIES:
➢ According to learning theorists, children who later have schizophrenia have irrational
reactions and ways of thinking by imitating parents who have their own significant
irrational problems Schizophrenia as a result of poor models of learning during
childhood

B) LIFE EVENTS:
➢ Life events and difficulties have been put forward as precipitants of schizophrenia
➢ Paykel (1978) calculated that experiencing a life event doubles the risk of developing
schizophrenia over the subsequent 6 months

C) SOCIO CULTURAL FACTORS:

Some of the social factors relevant in the etiology of schizophrenia are:

1) Social class and mobility:
➢ One of the most widely accepted hypothesis is that
o schizophrenia is distributed unevenly among social class.
➢ In general investigations of the relationship of social class to schizophrenia have
pursued 2 main themes.
➢ The social status at the time he became ill
➢ Ecological characteristics of his community
➢ Studies reveal that the highest incidence of schizophrenia especially in women occurs
in the lower social class.

Breeder hypothesis:
LSES & central area leads to increased social & economic stress and to Schizophrenia.

2) Migration:
➢ The effect of migration has been studied more extensively than any other parameter
of social change.
➢ High prevalence and increased chances of hospitalization had been found in immigrant
population

3) Social Isolation:

➢ In 1939 Faris & Dunham considered that this social isolation and pre-psychotic drift to
areas of social isolation play a part in the causation of an increased incidence of
schizophrenia in areas with marked isolation

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4) STRESS DIATHESIS MODELS:
➢ It stresses the interactions of early events (whether genetic, biological, or social) with
later stressors (e.g life events)
➢ The early factors confer vulnerability to schizophrenia, whereas the latter explain its
onset and course

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 Social Theories of Suicide

Dr Subbulakshmi Kota

Theories of suicide:
1. Biological -emphasis on genetic and disease process
2. Psychological- emphasis on personality and coping deficits
3. Social - emphasis on social and environmental factors

SOCIAL THEORIES OF SUICIDE

DURKHEIMS THEORY:
Durkheim's definition:
➢ Suicide is applied to all cases of death resulting directly or indirectly from a positive or
negative act of the victim himself, which he knows will produce this result
➢ He postulated two variables as important causes of suicide:
1. Social integration - the extent to which members of society are bound together in
social networks
2. Social regulation - the extent to which the behaviour, desires, and emotions of the
members of the society are regulated by the society
Types:
(1) Egoistic suicide: Weak integration
➢ According to Durkheim, when a man becomes socially isolated or feels that he has no
place in the society he destroys himself
➢ This is the suicide of self-centred person who lacks altruistic feelings and is usually cut
off from main stream of the society
➢ People without social bonds and thought that their death would not affect society, so
felt it was easier to do so. (an example of this could potentially be an outlier of society,
a drug taker etc.)

(2) Altruistic suicide: Over integration

➢ This type of suicide occurs when individuals and the group are too close and intimate
➢ A person is so integrated they have no life of their own, the only way to gain back their
life is by ending it
➢ This kind of suicide results from the over integration of the individual into social proof,
for example - Sati customs, Dannies warriors

(3) Anomic suicide: Weak regulation in society

➢ This type of suicide is due to certain breakdown of social equilibrium, such as, suicide
after bankruptcy or after winning a lottery
➢ In other words, anomic suicide takes place in a situation which leads to sudden
changes
(4) Fatalistic suicide: Over regulation in society

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 ➢ People feel incarcerated and the only way they see to gain back control / escape is by
death.
➢ Under the overregulation of a society, when a servant or slave commits suicide, when
a barren woman commits suicide, it is the example of fatalistic suicide

DOUGLAS
➢ Douglas argues that sociological analysis should focus on meaning rather than social
structure
➢ He stresses on the meaning of suicide for the person assessed by using diaries,
suicide notes, psychiatrists notes and biographies
➢ He suggests a number of typical meanings like:

• Suicide as reunion
• Suicide as atonement
• Suicide as revenge

BAECHLERS
Uses a similar approach to Douglas, he identifies four main types:

1. Escapist - from intolerable situations such as grief or punishment

2. Aggressive - an attempt to harm others
3. Oblative - as sacrifice, or to attain a desired state in others' opinion
4. Ludic - as a test to prove oneself

TAYLOR
➢ Taylor uses a case study approach to present an essentially Durkheimian theory of suicide
➢ Taylor suggests that suicide is the consequence of an imbalance between two factors in
individuals' lives; certainty and uncertainty; and detachment and attachment to others
• Certainty/uncertainty:
➢ Suicides are more likely in situations of complete uncertainty where an individual feels
they know nothing worth knowing, or in situations of complete certainty where an
individual feels they know everything worth knowing
➢ Uncertainty leads to the ordeal a suicide attempt is undergone as a judgement by fate.
Certainty leads to a wholehearted attempt to end life
• Attachment/detachment:
➢ Suicides are more likely when individuals are either psychologically immune from the
opinions of others, or are unprotected from the opinions of others
➢ Immunity produces detachment, over-dependence produces attachment where the
opinions of others make it impossible to go on living

Taylor's analysis leads to the development of a structural theory, which distinguishes

between four basic meanings, caused by a combination of certainty/uncertainty and
attachment/detachment:
1. Thanatation: (uncertainty and detachment)
➢ An individual feels their existence is problematic to themselves and others
cannot tell the individual what they want to know

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2. Submission (certainty and detachment)
➢ An individual feels their existence is over and others cannot persuade them
from what they know
3. Appeal – (uncertainty and attachment)
➢ An individual feels they know nothing worth knowing and others' lack of concern
makes existence problematic
4. Sacrifice – (certainty and attachment)
➢ An individual feels they know everything worth knowing and others have made
it impossible to go on living

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 Define emotion, theories of emotions and discuss the neurophysiology
of expression of emotion

Dr Subbulakshmi Kota

Introduction:

➢ The word emotion is adapted from the French word émouvoir, which literally means,
“to stir up”
➢ Emotion is a subjectively experienced feeling that is related to affect and mood
➢ The experience of emotion occurs through a set of expressive behaviors, the function
of the nervous system, and cognitive perception or appraisal
➢ Emotion has behavioral, somatic, and psychic components
➢ Basic facial expression of emotions seems to be consistent across human populations,
possibly owing to their adaptive value in evolution
➢ These include Happy, Sad, Fear, Anger, Surprise and Disgust
Different theories of generation of emotions:

➢ They are explained in terms of the interactions between their components:

➢ An emotion-arousing stimulus, a response of physiological arousal, a response of
cognitive appraisal, and the subjective experience of emotion
James-Lange theory:

It postulates that the bodily changes follow directly the perception of the stimulus, and that our
feeling of the same changes as they occur is the emotion

Cannon-Bard theory:

It proposed first by Cannon and later extended by Bard, the stimulus leads to both the arousal
and the emotion

Two-factor theory proposed by Schachter and Singer:

The stimulus leads to the arousal that is labelled using the cognition that leads to the emotion

Cognitive-appraisal theory:

➢ Proposed by Lazarus, the stimulus leads to the personal meaning arrived at using
cognition that leads to both the arousal and the emotion
➢ The appraisal model suggests that an evaluation or appraisal of the environment is
connected to the initial stimulus preceding and modifying the emotion.

471
A modification of this theory is the modal model of emotion that has three elements:

1. Emotions arise when an individual attend to a situation and sees it relevant to their
goals
2. Emotions result in changes in subjective experience, behavior, and central and
peripheral physiology
3. A response that may be modulated
Emotions are regulated by five families of processes:

1. Situation selection
2. Situation modification
3. Attentional deployment
4. Cognitive change
5. Response modification
Neurobiology of emotion perception:

Emotion perception can be understood in terms of the following processes occurring after the
initial presentation of an emotive stimulus, which then allows the generation of complex
affective states, emotional experiences (feelings), and behaviors:

1. The appraisal and identification of the emotional significance of the stimulus

2. The production of a specific affective state in response to the stimulus, including autonomic,
neuroendocrine, and somatomotor (facial, gestural, vocal, behavioral) responses, as well
as conscious emotional feeling, which may bias process toward the identification of specific
categories of emotional stimuli

3. The regulation of the affective state and emotional behavior, which may involve an inhibition
or modulation of processes 1 and 2, so that the affective state and behavior produced are
contextually appropriate

These processes may be dependent upon the functioning of two neural systems:

1. The ventral system:

➢ Comprises of amygdala, insula, ventral striatum, and ventral regions of the anterior
cingulate gyrus and prefrontal cortex
➢ Function:
o Identification of the emotional significance of environmental stimuli and the
production of affective states.
o Automatic regulation and mediation of autonomic responses to emotive stimuli and
contexts accompanying the production of affective states.
2. The dorsal system:

➢ Comprises of hippocampus and dorsal regions of the anterior cingulate gyrus and
prefrontal cortex regions
➢ Functions:
o Cognitive processes are integrated with and can be biased by emotional input, is
important for the performance of executive functions, including selective attention,
planning, and effortful rather than automatic regulation of affective states.

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o Finally, evidence from studies examining ventral and dorsal anterior cingulate gyral
activity suggests a reciprocal functional relationship between these two neural
systems.
o Different patterns of structural and functional abnormalities, particularly within the
ventral system, exist within mood disorders and schizophrenia which are
responsible for the generation of specific symptoms

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 Process of learning and its effect on behaviour/ Discuss types
of learning and application of behaviour therapy to various
psychiatric disorders

Dr Subbulakshmi. k

Definition:
➢ Learning is defined as a relatively permanent change in behavior that occurs as a result
of practice or experience
➢ 3 elements in definition:
1. Change for better or worse
2. Through practice or experience not due to growth or maturation
3. Change is relatively permanent

Theories of learning:
1.Behaviourism
2.Cognitive learning
3.Social learning
4. Other theories include:
➢ Constructivism
➢ Multiple Intelligences
➢ Brain-Based Learning

Behaviourism:
Conditioning: Acquiring of fairly specific patterns of behaviors in the presence of well-defined
stimuli
CLASSICAL CONDITIONING:
In classical conditioning learning is thought to take place as a result of the contiguity of
environmental events. Also, known as pavlovian or respondent conditioning

Basic Steps:
Before conditioning:
Bell ————————> No salivation
(Neutral stimulus, NS)

Food ——————————> Salivation

(Unconditional stimulus, US) (Unconditioned response, UR)

During conditioning:
Bell : Food————————————> Salivation
(NS) (US) (UR)

After conditioning:
Bell ——————-————————————-> Salivation
(CS) (CR)

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 ➢ Unconditioned Stimulus (UCS): A stimulus that can evoke an unconditioned
response the first time it is presented.
➢ Unconditioned Response (UCR): A response evoked by an unconditioned stimulus.
➢ Conditioned Stimulus (CS): A stimulus that is repeatedly paired with an
unconditioned stimulus.
➢ Conditioned Response (CR): A response to the conditioned stimulus.

Basic Principles:

1. Acquisition:
➢ The process by which a conditioned stimulus acquires the ability to elicit a conditioned
response through repeated pairings of an unconditioned stimulus with the conditioned
stimulus.
➢ Factors that influence conditioning:
Temporal arrangement of the CS–UCS pairings
Temporal arrangement of the CS–UCS pairings:
Temporal means time-related:
the extent to which a conditioned stimulus precedes or follows the presentation of an
unconditioned stimulus.
Delayed conditioning:
A form of forward conditioning in which the presentation of the unconditioned stimulus
(UCS) begins while the conditioned stimulus (CS) is still present

Trace conditioning: A form of forward conditioning in which the onset of the

conditioned stimulus (CS) precedes the onset of the unconditioned stimulus (UCS) and
the CS and UCS do not overlap

Simultaneous conditioning: A form of conditioning in which the conditioned stimulus

(CS) and the unconditioned stimulus (UCS) begin and end at the same time

Backward conditioning: A type of conditioning in which the presentation of the

unconditioned stimulus (UCS) precedes the presentation of the conditioned stimulus
(CS)

Stimulus interval between CS-UCS:

In animal research, the optimal CS–UCS interval seems to be between 0.2 and 2
seconds; longer intervals make it difficult for animals to recognize the conditioned
stimulus as a signal for some future event.

2. Extinction:

The process through which a conditioned stimulus gradually loses the ability to evoke
conditioned responses when it is no longer followed by the unconditioned stimulus

3.Spontaneous recovery:
Following extinction, return of a conditioned response upon reinstatement of CS–UCS pairings

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4. Stimulus generalization:
The tendency of stimuli similar to a conditioned stimulus to evoke conditioned responses

5. Stimulus discrimination:
The process by which organisms learn to respond to certain stimuli but not to others.

APPLICATIONS:
➢ Most behaviours are acquired through classical conditioning. Behaviour is learnt
➢ Hence can be unlearned.
➢ Used in understanding acquisition of ‘normal’ and ‘abnormal behaviour’
E.g. : Acquisition of habits and fears
➢ Irrational fears & anxieties are conditioned & can be unlearned through conditioning.

A) Systematic Desensitization as treatment modality: (Joseph Wolpe, 1958)

➢ Phobia: Proposed to be acquired by classical conditioning
➢ Teach the person relaxation techniques
➢ Create hierarchy of fear eliciting stimuli from least to most strong example of stimulus
➢ Gradually (from least to most) pair each item of hierarchy with relaxation techniques
without producing fear.
➢ Combines counter conditioning, generalization, and extinction

B) Flooding:
➢ It is another exposure technique based on classical conditioning
➢ While graduated exposure may use other types of exposure, such as visualization
techniques or imagination, flooding uses actual exposure to the feared stimulus at a
greater than usual level
➢ Under controlled conditions, a patient is placed in contact with the stimulus that
provoked the original trauma
➢ The therapist helps the patient use relaxation techniques in order to calm themselves
➢ The theory, of course, is that the patient comes to associate a relaxation response with
the objects that previously caused fear

C)Aversion therapy:
➢ It is another application of classical conditioning where a person with an unwanted
behavior learns to associate the unwanted behavior with an unpleasant event
➢ For example, in order to get you to stop biting your fingernails, a substance that tastes
very bitter might be painted on your fingers so that every time you bite your nails, you
taste something horrible

OPERANT CONDITIONING:
Operant conditioning is a form of learning in which behavior is maintained, or changed, through
consequences.
Operant behavior:
Behavior designed to operate on the environment in a way that will gain something desired or
avoid something unpleasant.
Reinforcement:

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To present a stimulus that increases the probability that the preceding response will recur in
the future

Processes which increase the likelihood of response:

1. Positive Reinforcement:
➢ Consist of presentation of a stimulus (one that is pleasant or rewarding) following
a response, which then leads to an increase in the future strength of that response
2. Negative reinforcement:
➢ Removal of a stimulus (one that is considered unpleasant or aversive) following a
response, which then leads to an increase in the future strength of that response

Processes which decrease the likelihood of response:

Punishment:
The presentation of a stimulus (one that is usually considered unpleasant or rewarding)
following a response, which then leads to a decrease in future strength of that response

Omission of reinforcement:
Consist of removal of a stimulus (one that is usually considered pleasant or rewarding)
following a response, which then leads to decrease in the future strength of that response

Schedules of Reinforcement:
Types: Continuous and intermittent schedule
Continuous:
A schedule of reinforcement in which every occurrence of a particular behavior is reinforced
Intermittent/partial:
One in which some responses are reinforced, helps in maintaining a behavior
Can be of following types:
1. Fixed-Interval Schedule
2. Variable-Interval Schedule
3. Fixed-Ratio Schedule
4. Variable-Ratio Schedule

Extinction:
Extinction takes place when the reinforcement is withdrawn
Unreinforced behavior terminates

Aversive Conditioning:
An organism changes its behavior to avoid a painful or aversive stimulus
Can be of 2 types:
Escape learning:
➢ An animal learns a response to get out of a place where it does not want to be
Avoidance Learning:
➢ The learned response is made before the onset of noxious event and prevents the
learner from being exposed to noxious event
➢ It requires an additional response

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 ➢ To move from escape learning to avoidance learning, an animal must make an
anticipatory response to prevent the punishment

Applications :

1.Contingency management:
➢ Functional analysis of behavior
➢ One of the first steps in implementing operant conditioning techniques in therapy
➢ Antecedent ——> Behaviour ———> Consequences
➢ Using this positive and negative reinforcers are identified
➢ Contingency contract is made

2.Extinction:
➢ It is used in time out from reinforcements (omission training).Inappropriate behavior
leads to timeout in an area with minimal positive reinforcement leading to reduction in
inappropriate behavior

3.Differential reinforcement:
➢ Giving positive reinforcement for desired behavior and withholding it in their absence
or in case of abnormal behavior
➢ Used in treatment of dissociative disorders apart from behavioral disturbances in
children

4. Token Economy:
➢ In token economy people earn objects which they can exchange for desirable items,
services or privileges
➢ Token economies have been used in classrooms, institutions, workshops,
rehabilitation centers
➢ A secondary reinforcer (a token) is given for good behavior
➢ Learner turns the token in for something more primary
➢ Star charts for child behavior also is a type of token economy

5. Shaping:
➢ Shaping is also called successive approximation
➢ Gradual nurturing of correct responses
➢ An operant procedure in which a desirable behavior pattern is learned by the
successive reinforcement of approximations to that behavior

6.Punishment:
➢ Use of a punisher to suppress or stop a behavior to occur in future
➢ Weakens one behavior and makes a desirable one more likely
➢ Loses effectiveness if almost everything child does is punished
➢ Disadvantage being it can be unconditioned stimulus of fear

Covert sensitization:
A useful alternative to physical punishment in which the unwanted behavior is imagined with
the imaginary punishing consequences

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SOCIAL LEARNING:
➢ Social learning theory (Albert Bandura) incorporates both classical and operant models
of learning, but also considers a reciprocal interaction between the person and the
environment
➢ Learning takes place through observation and sensorial experiences
➢ Observational learning, (also called social learning theory) occurs when an observer’s
behavior changes after viewing the behavior of a model
➢ An observer’s behavior can be affected by the positive or negative consequences–
called vicarious reinforcement or vicarious punishment– of a model’s behavior
➢ It is the basis of the movement against violence in media & video games

Application:
➢ Modeling techniques:
➢ Can be used in group or individual basis as in
1. Behavioural rehearsal
2. Role reversal
3. Social skills training
4. Medical self-help skills

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 Theories of motivation / Psychological theories of Motivation and their
Clinical relevance

Dr Subbulakshmi Kota

Introduction:

➢ Motivation is the process by which activities are started, directed and continued so that
physical or psychological needs or wants are met (Petri, 1996)
➢ Motivation refers to the driving and pulling forces which result in persistent behavior
directed toward particular goals.
Drive Theories (Drive reduction theories):

➢ Called as “push theories of motivation”

➢ Behaviour is pushed toward goals by driving states within a person or animal
➢ According to drive theory when an internal driving state is aroused, the individual is
pushed to engage which will lead to a goal that reduces the intensity of the driving
state
1) There is a driving state

2) A goal directed behaviour initiated by the driving state

3) Attainment of an appropriate goal

4) Reduction of the driving state and subjective satisfaction and relief when
goal is reached

➢ After a time, driving state builds up again to push behavior toward the goal
➢ This sequence of events is called as “The motivational cycle”
➢ Drive theories differ on the source of driving state
➢ Some theorists like Freud conceived of driving state as being inborn or instinctive
➢ Students of animal behavior, ethologists have proposed an elaborate set of inborn
driving mechanisms
➢ Other drive theorists emphasize role of learning in the origin of driving states
➢ Such learned drives originate in person’s training or past experience & thus differ from
one individual to another
INCENTIVE THEORIES

➢ In contrast to the push of drive theories, incentive theories are “Pull theories” of
motivation
➢ Because of certain characteristics of the goal/final result, they pull behaviour towards
them
➢ The goal objects which motivate behaviour are known as Incentives
➢ Individuals expect pleasure from the attainment of positive incentives and from the
avoidance of negative incentives

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OPPONENT PROCESS THEORY

➢ Hedonistic views of motivation say that we are motivated to seek goals that give
pleasure and avoid those which lead to displeasure
➢ This theory takes a hedonistic view
➢ Because of its views on what is pleasure and displeasure, it may be also called a theory
of emotion
➢ The tenet of this theory is that many emotional-motivational states are followed by
opposing states
OPTIMAL-LEVEL THEORIES

➢ This says that there is a certain optimal or best level of arousal that is pleasurable
called “just-right theories”
➢ The individual is motivated in such a way as to maintain the optimal level of arousal
➢ For instance, if arousal is too low, a person will seek situations or stimuli to increase
arousal
➢ If arousal is too high behaviour will be directed towards decreasing it
EXPECTANCY VALUE THEORIES

➢ These are a class of theories based on the work of Tolman & others
➢ These theories assume that actions of human cannot be predicted or fully understood
without understanding the beliefs, values and the importance a person attaches to
those beliefs and values at any given moment in time
➢ Cognitive expectancies- a set of beliefs about what will happen in the future based on
the past experiences
➢ Tolman’s (1932) work with animals showed that organisms are capable of
remembering what had happened in the past, anticipating future events & adjusting
their own actions according to those cognitive expectancies
HUMANISTIC APPROACH:

MASLOW’S HEIRARCHY OF NEEDS:

➢ Maslow proposed that there are several levels of needs that a person must strive to
achieve before achieving the highest level of personality fulfillment
➢ Self-actualization is the point seldom reached at when people have satisfied the lower
needs and achieved their full human potential
➢ Basic needs at bottom
➢ Highest needs at top
➢ Can be grouped from base of pyramid as Physiological, Safety, Love and belonging,
Esteem and top most of pyramid Self actualization

Self- Determination theory

➢ Proposed by Ryan & Deci (2000)

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 ➢ Here there are 3 inborn & universal needs that help people gain a complete sense of
self and whole healthy relationship with others:
1. Autonomy- need to be in control of one’s own behaviour (self-determination)
2. Competence- need to be able to master challenging tasks of one’s life
3. Relatedness- need to feel a sense of belonging, intimacy & security and
relationships with others
➢ This theory holds that satisfying these needs can be best done if there is a supportive
environment to develop goals & relationship with others
➢ This satisfaction fosters psychological growth and increase person’s intrinsic
motivation
➢ Intrinsic motivation- motivates person to perform an action because the act itself is
rewarding or satisfying in an internal manner
➢ Intrinsic motivation is increased when a person not only feels competence but also a
sense of autonomy or knowledge that his or her actions are self- determined rather
than controlled by others
➢ There are both elements of intrinsic & extrinsic motives in many things we do
TYPES OF MOTIVES

BIOLOGICAL MOTIVES:

Hunger, Thirst, Sexual drive, Maintenance of body temperature

SOCIAL MOTIVES:

➢ Social motives are so called as they are learned in social groups especially in family
and they involve other people
➢ These motives are general states that lead to many particular behaviours
➢ They determine what a person does and they persist not fully satisfied for long years
➢ Three of the most studied social motives are
1. Need for achievement
2. Need for affiliation
3. Need for power
➢ Measurement of social motives is done by studying common underlying themes by
using projective tests, personality tests, situational questionnaires.
Clinical relevance:

1. Drive theory:

➢ Biological motives work on the basis of drive theory-hunger ,thirst

➢ Withdrawal symptoms lead to driving state in substance dependence
2. Incentive theory:

Wages, bonus, rewards work in improvement of behavior or performance on the basis of

incentives theories

Pleasure as incentive can explain substance dependence

3. Expectancy value theory:

➢ Problem solving and decision making

➢ Social learning

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 ➢ Social motives
➢ Assessment of themes around social motives is used in Projective tests like TAT,
personality questionnaires and situational tests
4. Humanistic approach:

Can be used to explain the behavior and development of personality

483
 Culture and
Mental Illness

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 Culture and Mental disorders
How does culture influence psychopathology? significance of
culture in psychiatry

Dr Amitkumar Chougule

Definition:

➢ Culture refers to the meanings, values and behavioural norms that are learned and
transmitted in the dominant society and within its social groups
➢ Culture powerfully influences cognition, feelings, and self-concept as well as the
diagnostic process and treatment decisions
➢ It is the lens through which a person registers experiences that shape his/her
perceptions, understanding and reactions to events
Components of Culture:

1. Culture is learned
2. Culture can be passed on from one generation to the next
3. Culture involves a set of meanings in which words, behaviors have meanings agreed
upon by the cultural group
4. Culture acts as a template to shape and orient future behaviors
5. Culture exists in a constant state of change
6. Culture includes patterns of both subjective and objective components of human
behaviour
Impact of culture on Psychiatry:

➢ Culture shapes how and what psychiatric symptoms are expressed

➢ Culture influences the meanings that are given to symptoms
➢ Culture also impacts the interaction between the patient and the health care system
Transcultural Psychiatry:

“The discipline that deals with the description, definition, assessment and management of all
psychiatric conditions, as they reflect and are subjected to the influence of cultural factors in
a biopsychosocial context, while using concepts and instruments from social and biological
sciences, to advance a full understanding of psychopathology and its treatment.”

485
Evolution of Transcultural Psychiatry:

DIFFERENT WAYS IN WHICH CULTURE IMPACTS PSYCHOPATHOLOGY:

1. Patho-genic effects
2. Patho-selective effects
3. Patho-plastic effect
4. Patho-elaborative effects
5. Patho-facilitative effects
6. Patho-reactive effects
1. Pathogenic Effects:

➢ Pathogenic effects refer to situations in which culture is a direct causative factor in

forming or ‘generating’ psychopathology
➢ Cultural ideas and beliefs contribute to stress, which in turn produces psychopathology
➢ EXAMPLES:
DHAT SYNDROME
In INDIA ‘Harmful’ wastage of semen can produce anxiety , depression and somatic
symptoms
➢ KORO:
The folk belief that death will result if the penis shrinks into the abdomen
Found in Malaysia
➢ So, culture is the direct cause of psychopathology, not of disease per se

486
2. Patho-selective effect:

➢ Tendency of some people in a society, when encountering stress, to select certain

culturally influenced reaction patterns that result in the manifestation of certain
psychopathologies
e.g FAMILY SUICIDE’ observed in Japanese society (Ohara,1963)

➢ In Japan, cultural influences leads a family to choose, from among many alternative
solutions, to commit suicide together, forming the unique psychopathology
➢ Culture selecting certain coping patterns to deal with stress
3. Pathoplastic Effect:

➢ Pathoplastic effects refer to the ways in which culture contributes to the modeling or
‘plastering’ of the manifestations of psychopathology
➢ The content of delusions, auditory hallucinations, obsessions, or phobias are subject
to the cultural context in which the pathology is manifested
➢ Religious delusions and delusional guilt are primarily found in Christian societies than
Islamic, Hindus or Buddhist
➢ Patients from developing countries reported visual hallucinations more frequently than
those from developed countries (Varma et al., 1997)
4. Patho-elaborating effects:

➢ Certain behaviour reactions (either normal or pathological) may be universal

➢ These behaviours may become exaggerated to the extreme in some cultures through
cultural reinforcement (Simon,1996)
• Phenomenon of “Trance and possession state”
– It is a culturally sanctioned
– This could be described to the religious elaboration of association with
‘Atman’ and ‘Deities’
➢ Culture elaborating mental conditions into a unique nature
5. Patho-facilitative effects:

Facilitating effects of culture makes it easier for certain psychopathologies to develop and
increase their frequency in certain cultures

A liberal attitude towards weapons control may result in more weapon-related violence or
homicidal behaviour (Westermeyer,1973)

Cultural permission to consume alcohol freely may increase the prevalence of drinking
problems

6. Patho-reactive Effects:

Culture influences:

➢ How people perceive pathologies and label disorders

➢ How they react to them emotionally
➢ Guides them in expressing their suffering

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 • Culture shape folk responses to the clinical condition
• Better prognosis of schizophrenia in developing countries like India
• Family, social and cultural factors have Pathoreactive effects on schizophrenia
resulting in different prognosis

IMPACT OF CULTURE ON PSYCHODYNAMICS:

CULTURAL VARIABLES RELATED TO PSYCHODYNAMICS:

1. Dependency versus autonomy

2. Linguistic competence
3. Cognitive style
4. Social support system
5. Material culture
6. Psychological sophistication
CULTURAL VARIABLES RELATED TO PSYCHODYNAMICS:

1. Dependency versus autonomy

2. Linguistic competence
3. Cognitive style
4. Social support system
5. Material culture
6. Psychological sophistication

1. DEPENDENCY VERSUS AUTONOMY:

Dependence prone society:
1. Interdependence
2. Strong sense of identity with the primary group
3. Lesser idea of individuality, of individual rights and responsibility
4. Pity, sacrifice, submission and gratitude as character traits
5. Shame prone society
Autonomy prone society:
1. Clearly demarcated ego-boundaries
2. Control over one’s body, action, thoughts and emotions
3. Greater self-reliance
4. An acute sense of one’s rights, duties and responsibilities
5. Guilt prone society

2. LINGUISTIC COMPETENCE:
LANGUAGE:
➢ Language is itself the shaper of ideas, the programmer and guide for the
individual mental activity
➢ Language is a determinant of the conception of reality, a model shaping the
mind as well as a code connecting minds
➢ Language and thought develop together
➢ Linguistic “competence" is the speaker - hearer's intrinsic knowledge of his
language
➢ Linguistic “performance" is the actual use of language in a given situation

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 ➢ Linguistic competence is an innate attribute of mind

3. Cognitive Styles:
Cognitive styles represent the ways in which the mind:
➢ Perceives the environment
➢ Interprets it
➢ Draws conclusions about it
Individuals and cultures differ from each other in cognitive styles
The cognitive style can be characterized as "analytical" at one extreme and "synthetic " at
the other
4. SOCIAL SUPPORT SYSTEM:
➢ Differences across cultures in the social support system has impact on course and
outcome of mental illness
➢ The traditional and developing societies which are richer in social support network
have shown to have a better prognosis of severe mental illnesses
➢ A very fruitful area of research in this area is expressed emotions
➢ Expressed emotions like critical comments and hostility have been correlated with
adverse prognosis
5. MATERIAL CULTURE:
Culture consists of:
➢ Beliefs, values, norms and myths
➢ Physical environment which is comprised of artifacts like roads, bridges, buildings, etc.
➢ The nature of material culture has influence on psychopathology
➢ The same malevolent force is perceived as a:
1. Spirit of a ghost in a developing society
2. X-rays and radio waves in a technologically advanced society
6. PSYCHOLOGICAL SOPHISTICATION
➢ Psychological sophistication is the ability to see conflicts in intrapsychic terms
➢ Conflict is perceived as within the mind or between the components of the psychic
structure
➢ Psychological sophistication may be related to coping mechanisms and certain types
of neuroses like hysteria
➢ It may also give rise to high introspection as a mental attribute to understand and
resolve conflicts

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 List Culture bound syndromes. Write in detail of any two culture
bound syndromes

Dr Amitkumar Chougule

Definition:

Culture:

➢ Culture in this context refers to the ideas, values, habits and other patterns of
behaviour which a human group transmits from one generation to another
Culture bound syndrome: (CBS)

➢ Most widely accepted definition is proposed by Prince 1985 which states that
➢ “CBS is a collection of signs and symptoms which is restricted to a limited number of
cultures primarily by reasons of certain of their psychosocial features”
Culture-specific syndrome or Culture-bound syndrome:

➢ Combination of psychiatric and somatic symptoms that are considered to be a

recognizable disease only within a specific society or culture.
➢ ‘Episodic and dramatic reactions specific to a particular community – locally defined
as discreet patterns of behavior’ (Littlewood & Lipsedge, 1985)
ICD AND DSM:

The term culture-bound syndrome was included in DSM IV (1994) and ICD 10 (1992).

DSM IV culture-bound syndrome denotes:

➢ Recurrent
➢ Locality-specific patterns of aberrant behavior and troubling experience, that may or
may not be linked to a particular DSM-IV diagnostic category
➢ Indigenously considered to be "illnesses," or at least afflictions
➢ Generally limited to specific societies or culture areas
ICD 10

➢ ICD 10 categorizes culture bound syndromes in the Annex 2 and lists 12 culture bound
syndromes
➢ It lacks any diagnostic and cultural explanatory guidelines
DSM 5

Cultural concepts of distress - refers to ways that cultural groups experience, understand,
and communicate suffering, behavioral problems, or troubling thoughts and emotions

Three concepts—syndromes, idioms, and explanations

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Syndromes - clusters of symptoms and attributions that tend to co-occur among individuals
in specific cultural groups, communities, or contexts and that are recognized locally as
coherent patterns of experience.

Idioms - are ways of expressing distress that may not involve specific symptoms or
syndromes, but that provide collective, shared ways of experiencing and talking about
personal or social concerns

Explanations - are labels, attributions, or features of an explanatory model that indicate

culturally recognized meaning or etiology for symptoms, illness, or distress

Importance of cultural concepts –

• To avoid misdiagnosis

• To obtain useful clinical information

• To improve clinical rapport and engagement

• To improve therapeutic efficacy

• To guide clinical research

• To clarify the cultural epidemiology

Classification of CBS:

True CBS

Dissociative phenomena:

1. Amok (Malaysian)

2. Falling out or blacking out (Southern US and Caribbean)

3. Latah (Malaysians)

4. Pibloktoq (Arctic and subarctic eskimos)

5. Grisi siknis (Atlantic coasts of Nicaragua & Honduras)

6. Shin-byung (Korean)

Anxiety states:

1. Ataque de nervios

2. Dhat

3. Koro

4. Kayak angst

5. Taijin Kyofusho

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Affective/Somatoform disorders:

1. Brain fag

2. Shenjing Shuairuo

3. Anorexia Nervosa

4. Chronic Fatigue Syndrome

Psychotic states:

1. Boufee delirante
2. Qi-gong
Classification based on illness attribution:

1. Induced by anger – Bilis, Colera, or Muina & Hwa-Byung

2. Induced by fright – Susto & Kesambet

3. Induced by Witchcraft – Ghost sickness & Rootwork or voodoo

4. Induced by the “Evil eye” – mal de ojo

5. Induced by Percieved organic disturbance – Dhat & Sangue Dormida

6. Induced by possession

Idioms of distress

1. Nervios

2. Locura

In India, common culture bound syndromes are:

➢ Dhat Syndrome
➢ Possession Syndrome
➢ Koro
➢ Gilhari syndrome
➢ Bhanmati sorcery
➢ Compulsive spitting
➢ Culture-bound suicide (sati, santhra)
➢ Ascetic syndrome
➢ Jhinjhinia

DHAT SYNDROME (South Asia):

➢ Dhat derives from the Sanskrit word ‘Dhatu’ meaning ‘metal’ and also ‘elixir’ or
‘constituent part of the body’.
➢ First described in western texts by Wig (1960)
➢ Comprises vague somatic symptoms of fatigue, weakness, anxiety, loss of appetite,
guilt and sexual dysfunction attributed by the patient to loss of semen in nocturnal
emissions, through urine or masturbation

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The patient presenting with Dhat syndrome is typically more likely to be: (Indian story on
semen loss and related dhat syndrome; Om Prakash, Sunil Kumar Kar, TSS Rao)

➢ Recently married
➢ Of average or low socio-economic status (student, laborer or farmer by occupation)
➢ Comes from a rural area
➢ Belongs to a family with conservative attitudes towards sex

Management of Dhat syndrome: (Development of CBT for Dhat Syndrome; Abdul salam
K.P, Mahendra sharma, Om Prakash)

➢ Wig suggested emphatic listening, a non-confrontational approach, reassurance and

correction of erroneous beliefs, along with use of placebo, anti-anxiety and
antidepressant drugs whenever required
➢ Depressive symptoms of this syndrome showed effective response to SSRI along with
regular counselling
➢ Other intervention studies for Dhat suggest sex education, relaxation therapy and
medications.
➢ Sex education focuses primarily on anatomy and physiology of sexual organs

KORO:
Refers to an episode of sudden and intense anxiety that the penis (or, in women, the
vulva and nipples) will recede into the body and possibly cause death
The syndrome is reported in south and east Asia
Also known as :
• shuk yang, shook yong, and suo yang (Chinese)
• jinjinia bemar (Assam)
• or rok-joo (Thailand)

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 Explanatory Models:

1. Kraeplin(1921): hypochondriacal delusion seen in depressive illness

2. Yap(1965): depersonalisation syndrome manifesting as a body image
disturbance due to dissociative mechanism
3. Chowdhury: psychosexual conflicts lead to body image disturbance
4. Psychodynamic view: powerful symbol of loss of potency and power in the
male-depressive negative self-image

GILHARI SYNDROME

1. This population believed that it starts as feeling of Gilhari running on back of body
associated with intense pain and anxiety and finally Gilhari reaching the throat causing
stoppage of breathing
2. Gilhari syndrome is prevalent in Bikaner region
3. People believed that Gilhari must be crushed to death or it will kill patients and the
treatment is mainly received from local expert or faith healers
AMOK:

Syndrome indigenous to the Malayo-Indonesian cultural region

1. Men of Malay extraction.

2. Muslim religion
3. low education
4. rural origin
5. Between the ages of 20 and 45
Precipitants include:

1. Arguments with coworkers

2. Nonspecific family tensions
3. Feelings of social humiliation
4. Bouts of possessive jealousy
5. Gambling
6. Debts
7. Job loss
Clinical presentation:

➢ Exposure to a stressful stimulus or subacute conflict

➢ Feelings of anger, loss, shame, and lowered self-esteem
➢ A period of social withdrawal
➢ Transition
➢ Indiscriminate selection of victims
➢ Verbalizations
➢ Cessation
➢ Subsequent partial or total amnesia
➢ Perceptual disturbances or affective decompensations

494
Neuro-imaging in
Psychiatry

495
 NEURO-IMAGING IN PSYCHIATRY

1. Merits of available neuroimaging techniques and their applications in psychiatry

2. Neuroimaging in Psychiatry disorders both in clinical practice and also in biological
surgery research
Dr Amitkumar Chougule

INTRODUCTION:

Unlike many neurological disorders, psychiatric disorders do not cause changes visible to
the naked eye in the neuroimaging study of the individual patient

They are, however, amenable to investigation by recent neuroimaging modalities:

•Quantitative structural imaging, as exemplified by voxel-based morphometry

•Functional neuroimaging, using magnetic resonance imaging (MRI) techniques,
positron emission tomography (PET), and single photon emission tomography
(SPECT)
• Imaging genetics”): neuroimaging findings in two or more genetic variants of the
population are compared in order to discover imaging endophenotypes that may
be amenable to measurement, and, therefore, useful as biomarkers in therapeutic
discovery
NEUROIMAGING IN THE DIFFERENTIAL DIAGNOSIS OF NEUROPSYCHIATRIC
SYNDROMES:

• Neuroimaging may help arrive at the correct diagnosis in a patient presenting with
psychiatric symptoms.
• Such symptoms may be caused by neurological diseases masking as psychiatric
disorders or by disorders currently considered to be primarily psychiatric in nature.
• Neuroimaging to diagnose neurological diseases masquerading as psychiatric
disorders

496
• Neuroimaging is routinely used in the workup of patients with psychotic disorders
because lesions of the frontal or temporal lobes, most often tumors, can present with
psychosis
• In some cases, a behavioral syndrome is caused by focal seizures arising from a tumor,
notably oligodendroglioma, or from congenital or traumatic lesions.
• Psychotic features may also be found with thalamic or hypothalamic lesions
• Apathy caused by a frontal brain tumor may be mistaken for depression.
• In older people with cognitive impairment, it may be difficult to differentiate a
neurodegenerative disorder from depression. Neuroimaging may be helpful in this
situation by showing findings characteristic of Alzheimer’s disease (AD), diffuse Lewy
body disease, or one of the frontotemporal dementias
• AD is characterized by:
1. Medial temporal atrophy on MRI or X-ray computed tomography (CT)
2. Decreased metabolism in the parieto-temporal association cortex, and precuneus
on [18F] fluoro-deoxyglucose (FDG) PET
3. Amyloid deposition on Pittsburgh compound B (PET)
• The frontotemporal dementias, or other lobar dementia syndromes, can be identified
early on FDG PET by decreased metabolism in the affected region, which eventually
also shows atrophy on MRI.
• In a patient with impairment in various areas of cognition, likely to be attributable to
an attentional deficit, and with a normal result on the structural imaging study, a
negative result on the PET or SPECT study lowers the probability of a
neurodegenerative disorder.
• A negative [11C]-Pittsburgh compound B PET result will decrease the probability of AD
and dementia with Lewy bodies (DLB), but not of having a frontotemporal dementia
Neuroimaging in the diagnosis of psychiatric disorders:

Neuroimaging findings in psychiatric disease may lack specificity and often fail to reveal a
clear connection to a single neurobiological disturbance

Currently, the neuroimaging pattern determined in the study of a single psychiatric

patient does not allow for an accurate diagnosis. Some characteristic findings, however,
have been derived from samples of patients with each of the psychiatric diagnostic
groupings.

Schizophrenia:

1. Based on results from voxel-based morphometry or other quantitative structural

MRI techniques, the volume of the prefrontal, anterior temporal, and perisylvian
regions, as well as of the anteromedial thalamus, has been found to be decreased
even in first time psychotic episodes
2. However, similar structural changes can be affected by the use of antipsychotic
medication.

497
 3. Functional MRI (fMRI) or H2 15O PET scans have revealed abnormal activation in
the prefrontal and cingulate cortex and the medial temporal lobe.
Major depressive disorder:

1. Elevated frontal lobe metabolism but reduced volume has been found in the
subgenual region of the medial frontal lobe
2. Also, the activation pattern on fMRI has been found to distinguish depression from
degenerative disorders
3. Hippocampal activation during a memory task was found to be decreased in AD
patients compared with controls and depressed patients
4. In contrast, orbitofrontal and cingulate activation were greater in depressed
patients than in AD subjects or healthy controls.
5. Genotypic variants are likely to influence both the likelihood of developing major
depression and the imaging findings.
6. For instance, in depression, increased activity of the amygdala in response to
negative stimuli appears to be modulated by the 5-HT transporter gene (SLC6A4)
promoter polymorphism 5-HTTLPR.
7. Hippocampal volume loss is characteristic of elderly or chronically ill and
depressed individuals and may be impacted by the val66met brain-derived
neurotrophic factor gene variant and the 5-HTTLPR SLC6A4 polymorphism
8. In terms of neuro receptor PET imaging, major depression has been associated
with decreased 5-HT (1A) binding potential in the raphe nuclei, medial temporal
lobe, and medial prefrontal cortex.
NEUROIMAGING IN DRUG DISCOVERY AND DEVELOPMENT:

• Neuroimaging can be helpful at several levels of drug discovery and development:

1. Characterizing preclinical models
2. Early clinical studies to show that target engagement by the new drug induces the
biological changes expected to give clinical benefit
3. Clinical trials to demonstrate proof of concept (poc) or, in other words, that
engaging a particular target is linked to a meaningful change in a clinical endpoint
and thus proving the effectiveness of the drug being tried.
• Neuroimaging provides a window to observe “in vivo” brain structure and function,
both of which are likely to be abnormal in two of the commonest disorders affecting
humankind: depression and schizophrenia. As such, it could be an ideal biomarker in
therapeutic drug development.
• In general, neuroimaging can help in a number of the steps needed to determine the
properties of a candidate drug.
Role of functional imaging in Psychiatric disorders:

RESTING STATE STUDIES:

498
 1. Early functional neuroimaging studies investigated brain activity in patients who
were in the ‘resting state’.
2. The most robust finding in studies of resting cerebral blood flow (CBF) or
metabolism in schizophrenia was decreased activity in frontal cortex (termed
‘hypofrontality’) relative to controls.
3. However, some studies did not find differences between patients and controls in
resting frontal activity, and others reported ‘hyperfrontality’.
COGNITIVE ACTIVATION STUDIES:

1. Using fMRI, Curtis et al found that while patients with schizophrenia showed less
prefrontal activation than controls during verbal fluency, activation in the same
groups did not differ when they performed a semantic decision task
2. Using a graded memory task, Fletcher et al (5) demonstrated that patients with
schizophrenia showed normal prefrontal activation until the demands on working
memory were high and their performance deteriorated.
3. There is also evidence that prefrontal activation can vary with the mental state of
the patient at the time of scanning
4. Fu et al found that the degree to which prefrontal activation was reduced in
patients with schizophrenia was related to the severity of positive symptoms of
psychosis
STUDIES MEASURING SYMPTOMS ON-LINE

1. A relatively direct way of exploring the relationship between psychopathology and

brain activity is to scan patients while they are actually experiencing a given symptom
2. In schizophrenia, this approach has been used in several studies of auditory
hallucinations.
3. Studies using SPECT, PET and fMRI have tried to capture the pattern of brain activity
while patients were perceiving auditory hallucinations
4. studies highlighted the involvement of different areas, such as the left inferior frontal
cortex, the anterior cingulate gyrus, the lateral temporal cortex, and subcortical nuclei
5. obsessive-compulsive symptoms have been provoked in the scanner by presenting
patients with obsessive-compulsive disorder (OCD) with potential contaminants (that
elicit handwashing), and have been associated with activation in orbitofrontal and
cingulate cortex, and in the striatum
6. Words, pictures, and sounds redolent of traumatic events have been employed to
provoke symptoms in patients with post-traumatic stress disorder (PTSD) which have
been associated with decreased medial prefrontal and inferior frontal activation.
TREATMENT STUDIES

1. Functional imaging provides an opportunity to assess the effects of clinical treatments

on brain function.

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 2. Patients can be scanned before and after treatment, and changes in brain activity
pattern may be related to improvements in symptoms and/or cognitive function
within the same subjects

Clinical applications of imaging:

1. There is some evidence that the treatment of OCD and depression can normalize
increased regional brain metabolism. Moreover, the severity of pretreatment
abnormalities in these disorders can help to predict which patients will respond to
treatment
2. In schizophrenia, there is evidence that the severity of volumetric abnormalities (gray
matter volume) in first episode patients are associated with a relatively poor prognosis

Other work with structural MRI suggests that subjects with prodromal signs of psychosis who
later develop psychosis differ from subjects who do not, in having reduced gray matter
volume in the prefrontal, cingulate, and medial temporal

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 Define Intelligence and various theories of
intelligence/Assessment of intelligence

Dr Amitkumar Chougule

1. Introduction:

➢ Various definitions based on different parameters can be used to define and describe
intelligence
➢ No single definition is universally accepted, and no single test for overall global
intelligence
➢ Even defining intelligence can be difficult because your definition reflects your theory
of what it means to be intelligent, and theories of intelligence differ widely
2.Definition:

➢ Mental quality that consists of the abilities to learn from experience, adapt to new
situations, understand and handle abstract concepts, and use knowledge to
manipulate one's environment
➢ Wechsler also believed that ‘intelligence is the aggregate or global capacity of the
individual to act purposefully, to think rationally, and to deal effectively with his
environment’ (Wechsler, 1958)
3. Theories of Intelligence:

A. The Factorial approach:

➢ Here the Psychologists believe that the intelligence tests sample a number of mental
abilities that are relatively independent of one another
➢ One method of obtaining more precise information about the kinds of abilities that
determine performance on intelligence tests is factor analysis
➢ Factor analysis is a statistical technique that examines the intercorrelations among a
number of tests and, by grouping those that are most highly correlated, reduces them
to a smaller number of independent dimensions, called factors.
➢ The basic idea is that two tests that correlate very highly with each other are probably
measuring the same underlying ability

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➢ The goal is to discover the minimum number of factors, or abilities, required to explain
the observed pattern of correlations among an array of different tests

a. Charles spearman’s (1904) “g” factor:

➢ Originator of factor analysis

➢ Spearman (1904) first proposed that all individuals possess a general intelligence
factor (called g) in varying amounts
➢ A person could be described as generally bright or generally dull, depending on
the amount of ‘g’ he or she possessed
➢ According to Spearman, the ‘g’ factor is the major determinant of performance on
intelligence tests
➢ In addition, special factors, each called ‘s’, are specific to particular abilities or tests
➢ An individual’s tested intelligence would reflect the amount of g plus the magnitude
of the various s factors possessed by that individual
b. Louis Thurstone (1938), Primary Mental Abilities(PMA):

➢ Objected to Spearman’s emphasis on general intelligence,

➢ Suggested that intelligence can be divided into a number of primary abilities by
using factor analysis
➢ Thurstone identified seven factors, which he used to construct his Test of
Primary Mental Abilities
➢ MNOPQRS: Memory, Number, wOrd fluency, Perceptual speed, verbal
Qomprehension, Reasoning, Space
➢ Criticism:
1. Primary abilities are not completely independent
2. Significant intercorrelations among them provide support for the
concept of a general intelligence factor underlying the specific abilities
3. The number of basic abilities identified by factor analysis depends on
the nature of the test items
4. Other investigators, using different test items and alternative methods
of factor analysis, have identified from 20 to 150 factors representing
the range of intellectual abilities

c. Alternatives and Criticisms

➢ The existence of a single quantifiable factor for human intelligence has

been highly debated
➢ Criticism came from one of Spearman’s own students, Raymond
Cattell, who thought that intelligence could be understood as two main
capacities: “fluid” (Gf) and “crystallized” (Gc). Cattell thought that
crystallized intelligence was a kind of cemented knowledge bank
acquired over time, representing all those abilities that were already
familiar from previous learning. On the other hand, fluid intelligence was
the ability to acquire that knowledge in the first place, i.e. to learn in the
moment. He saw g as more accurately Gc, and that tests focusing only
on g would omit an important developmental factor in human
intelligence.

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 ➢ Others were similarly critical for the reductive nature of g, including
psychologist L.L. Thurstone and J. P Guilford. Both believed that there
were several, irreducible and independent domains of intelligence
➢ More criticism came from Howard Gardener who proposed nine
domains of intelligence, including some decidedly non-cognitive ones
like musical, existential and bodily-kinesthetic intelligence.

B. CONTEMPORARY/ MODERN THEORIES OF INTELLIGENCE:

➢ Rather than trying to explain intelligence in terms of factors, this approach

attempts to identify the mental processes that underlie intelligent behaviour
➢ It assumes that individual differences on a given task depend on the specific
processes that different individuals bring into play and the speed and accuracy
of those processes
➢ The goal is to use an information-processing model of a particular task to
identify appropriate measures of the processes used in performing the task

1. Gardner’s theory of multiple intelligences:

➢ Howard Gardner (2004a) developed his theory of multiple intelligences as a direct

challenge to the ‘classical’ view of intelligence as a capacity for logical reasoning
➢ Gardner was struck by the variety of adult roles in different cultures
➢ His observations led him to conclude that there is not just one underlying mental
capacity or ‘g’, but a variety of intelligences that work in combination
➢ He defines an intelligence as the ‘ability to solve problems that are of consequence in
a particular cultural setting or community
➢ It is these multiple intelligences that enable human beings to take on such diverse roles
as physicist, farmer, shaman, and dancer
➢ Gardner’s Seven Intelligences:
1. Linguistic Intelligence
2. Musical Intelligence
3. Logical mathematical Intelligence
4. Spatial Intelligence
5. Bodily kinesthetic Intelligence
6. Intrapersonal Intelligence
7. Interpersonal intelligence
Criticism:

1. High levels of ability in any of the various intelligences are usually correlated with high
ability in the others
2. No specific intellectual capacity is wholly distinct from the others

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 3. Mike Anderson points out that Gardner’s multiple intelligences are ill-defined – they
are sometimes a behaviour, sometimes a cognitive process, and sometimes a
structure in the brain

2. Anderson’s theory of intelligence and cognitive development:

➢ Anderson’s theory of intelligence holds that individual differences in intelligence
and developmental changes in intellectual competence are explained by
different mechanisms
➢ Differences in intelligence result from differences in the ‘basic processing
mechanism’ that implements thinking, which in turn yields knowledge
➢ Individuals vary in the speed at which basic processing occurs
➢ A person with a slower basic processing mechanism is likely to have more
difficulty acquiring knowledge than a person with a faster processing
mechanism
➢ This is equivalent to saying that a low-speed processing mechanism produces
low general intelligence
➢ According to Anderson, intelligence includes two ‘specific abilities’
➢ One of these deals with propositional thought (language mathematical
expression) and the other with visual and spatial functioning

3. Sternberg’s triarchic theory:

In contrast to Anderson’s theory, Robert Sternberg’s triarchic theory addresses

experience and context as well as basic information-processing mechanisms

His theory has three parts or subtheories:

1. Componential subtheory,: deals with thought processes;

2. Experiential subtheory: deals with the effects of experience on intelligence
3. Contextual subtheory: considers the effects of the individual’s environment and
culture
The most highly developed of these subtheories is the componential subtheory

The componential theory considers the components of thought. Sternberg has

identified three types of components:

1. Metacomponents are used to plan, control, monitor and evaluate processing

during problem solving
2. Performance components carry out problem-solving strategies
3. Knowledge-acquisition components encode, combine and compare
information during the course of problem solving
Criticisms:

1. Some critics claim that Sternberg’s theory has so many parts that it is not
coherent
2. Others note that it does not show how problem solving occurs in everyday
contexts
3. Others point out that it largely ignores the biological aspects of intelligence
4. Ceci’s bioecological theory:

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 ➢ It proposes that there are ‘multiple cognitive potentials’, rather than a single underlying
general intelligence or g
➢ These multiple abilities, or intelligences, are biologically based and place limits on
mental processes
➢ Their emergence, however, is shaped by the challenges and opportunities in the
individual’s environment, or context

5. Hebb:

➢ Type A: genetically-based potential

➢ Type B: effective intelligence

6. Cattell:

1. Fluid ability:
➢ Used for novel situations/problems
➢ Basis of initiative and creativity
2. Crystallized ability:
➢ Relies on prior learning and use of previous experience/knowledge

Assessment:

Psychometric methods:

Define and examine specific and general abilities, e.g. visual and verbal factors of intelligence.
Performance correlates between specific factors, but it is difficult to say how many factors
there should be (i.e. how many aspects there are to intelligence)

Computational methods:

➢ Examine the information processing involved in problem solving

➢ Five components suggested (Sternberg): TRAMP
➢ Transfer; Retention and Acquisition components, which deal with transfer of
knowledge, memory and learning
➢ Meta-components, which decide upon selection of strategies
➢ Performance components, which carry these out
Biological aspects e.g. heritability, diet

Cultural aspects e.g. emphasis on education/learning

Developmental aspects e.g. degree of stimulation in formative years

Attainment: achievement; consequence of learning

Aptitude: potential ability

Intelligence quotient (IQ):

➢ Percentage ratio determined by mental age (MA; measure of intellectual ability devised
by Binet) and chronological age (CA): IQ =(MA/CA)100.

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➢ Assessments designed such that average MA score equals CA, providing a mean IQ
of 100 (standard deviation 15)
➢ Intelligence assumed to have a normal distribution
➢ Measured intelligence increases up to 16 years of age, then plateaus from 16 to 25
years, followed by gradual decline until 5 years prior to death, when there is a terminal
drop

INTELLIGENCE TESTS
ADULTS
Wechsler Adult Intelligence Scale (WAIS) [revised (WAIS-R)]:
➢ For those aged 16 years and over
➢ Consists of 6 verbal and 5 performance subtests, providing verbal and
performance IQs
Verbal: SAD VIC
1. Similarities
2. Arithmetic
3. Digit span
4. Vocabulary
5. Information
6. Comprehension
PerfOrmance: ABCD
1. Object assembly
2. picture Arrangement
3. Block design
4. picture Completion
5. Digit symbol
➢ Scores are summed to provide overall IQ
➢ Performance scale more sensitive to normal ageing than verbal scale
➢ A large difference between verbal and performance scores renders overall test
interpretation invalid

2. Halstead-Reitan Neuropsychological Battery (HRNB):

➢ For ages 15 and over
➢ Designed to be a comprehensive neuropsychological assessment, typically
in cases of brain damage
➢ Comprises 10 individual tests and the possible addition of WAIS and/or
MMPI
3.National Adult Reading Test (NART):
➢ Estimates pre-morbid IQ using lists of words with difficult/obscure
pronunciation
➢ Not a direct measure, but pronunciation has been shown to be positively
correlated with intelligence
4.Mill Hill Vocabulary Test: based on recognition and recall
5.Raven’s Progressive Matrices:
➢ Involves diagram completion
➢ Different tests for different age groups
➢ Does not rely on recall and easy to use; less sensitive to cultural differences
and can be used for those with communication difficulties

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 ➢ Measures aptitude

CHILDREN:

1. Stanford–Binet Intelligence Scale:

➢ From 2 to 15 years
➢ Tests short-term memory and reasoning (verbal, quantitative, abstract, visual)
➢ IQ is derived by comparison with normative data
2. Wechsler Pre-school and Primary School Intelligence Scale (WPPSI):

➢ From 4 to 61/2 years

➢ Verbal and non-verbal
3.Wechsler Intelligence Scale for Children (WISC) [revised (WISC-R)]:

➢ From 5 to 15 years
➢ Verbal and non-verbal
4.Reitan-Indiana Neuropsychological Battery for children:

➢ From 5 to 8 years
5. Halstead Neuropsychological Battery for children:

➢ From 9 to 14 years

INTELLIGENCE TESTS AFFECTED BY:

1. Individual factors: Anxiety, motivation

2. Situational factors: Interaction with assessor (e.g. hostility)
3. Test factors: Age specificity (children especially), function/purpose specificity

References:
1. Atkinsons and Hilgards. Introduction to psychology. 15TH edition. Nolen-
Hoeksema,Fredrickson, Loftus, Wagenaar. Hampshire, United Kingdom: Cengage
Learning EMEA. 2009. 432-440
2. GIN S. MALHI, SAJ MALHI. Examination Notes in Psychiatry. 2nd edition. London: Oxford
University Press Inc. 2006. Page 31-40

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 Intelligence (Themes and variations)

Dr Amitkumar Chougule

Nature Vs Nurture:

Galton –
➢ He was the first to systematically assess intelligence
➢ Galton was a relative of Darwin and observed that success runs in families
➢ He thus concluded that hereditary factors as important for intelligence
➢ He tried to measure intelligence by sensory processing based on the theory that
exceptionally bright people should have exceptional sensory acuity
➢ He proposed the concept of eugenics
➢ He encouraged intellectually superior people to mate together to improve human race
➢ He also advised that lower socio-economic people must be prevented from procuring
children
➢ He gave the term nature Vs nurture and also gave the statistical concept of correlation

Binet:
➢ He was a French psychologist and was given the task to devise a test to identify
children who needed special education
➢ So Binet devised the test which later came to known as Binet – Simon scale and
expressed child’s intelligence in terms of mental age
➢ It did not give any number like quotient and so it was difficult to make out whether a
mental age of 6 in a 9 year old boy is better than mental age of 9 in a 12 year old boy

Terman:
➢ He was a psychologist at Stanford and he translated and revised the Binet test and
renamed it as Stanford- Binet intelligence scale
➢ He gave the concept of Intelligence quotient and expressed it by using a formula by
which comparisons were possible
➢ The tests were mainly useful in children and not to adults

Weschler:
➢ He was psychologist at NewYork and was working with adult patients
➢ He devised the scale to measure intelligence in adult patients which included both
verbal and nonverbal components
➢ Thus the scores were given as verbal IQ, Performance IQ and full scale IQ

Heritability:

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Twin studies:
➢ Twin studies have shown that intelligence correlation between identical twins (0.86)
greater than the fraternal twins (0.6)
Adoption studies:
➢ Correlation of intelligence between identical twins reared apart (0.72) is still greater
than the fraternal twins (0.6)
➢ These studies support that the interaction between genetic and environment is
important in the formation of intelligence
➢ The issue is mainly whether the genetic factors have 50% influence or 80% influence
Burt:
➢ He was a British psychologist and conducted studies on heritability of intelligence
➢ He studied the intelligence of twins reared apart and concluded that the correlation
was around 0.86 which was similar to other studies
➢ He was the main person behind the theory that under privileged youngsters should be
excluded from higher education
➢ However, later his studies fell into dispute because of the claim that some of his data
were fabricated
Sandra Scarr:
➢ Gave the concept of reaction range
➢ Reaction range refers to genetically determined limits on intelligence or other traits
➢ The upper and lower limits of intelligence are genetically determined and environment
decides where the individual falls within this range
➢ By environmental deprivation, individual may fall below the set lower limit however
even with significant environmental contribution cannot move above the upper limit

Cultural concepts
Jensen:
➢ Proposed that across different ethnicities there is a difference in intelligence
➢ He gave the facts that inspite of 50 years of training African Americans still had lower
levels of IQ when compared to Whites
Kamin:
➢ The concepts by Jensen received sharp criticisms that within the culture there are
significant variations in IQ and it depends upon whether a proper environment is
provided or not
➢ She explained this with the example of differences in height achieved by seeds planted
in barren land Vs fertile land
Stereotyped vulnerability – Steele:
➢ Proposed that minorities and woman are victims of some stereotypes and even in the
absence of overt discrimination there is prejudice
➢ These will manifest when the subject has to take the test with significant outcome and
the anxiety associated prevents an optimum performance

Concepts in intelligence:
Spearman-g factor:
➢ By way of factor analysis of earlier IQ test results, he was able to come to a conclusion
that most of the intelligence dimensions are interrelated and have significant overlap

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 ➢ He called this as “g” factor and has been the focus of most of the IQ tests to tap this g-
factor as much as possible
➢ Also biologically oriented theorists attribute significant genetic contribution to g-factor

Thurston and Guildford:

➢ Considered that a single g-factor is not capable of explaining the intelligence and
concluded that there are multiple abilities in intelligence
➢ Thurstone divided intelligence into seven distinct primary mental abilities and Guildford
expanded them to 150 separate abilities

Catell and Horn - Fluid intelligence and crystallized intelligence

➢ Fluid intelligence consists of reasoning ability, speed of information processing and
memory capacity.
➢ Crystallized intelligence consists of application of these acquired skills and knowledge
into problem solving.
➢ The 1986 version of Stanford – Binet test gives scores according to this model; there
is a composite score and 4 subset scores namely verbal reasoning, short term
memory, quantitative reasoning, abstract and visual reasoning. This is a significant
deviation from earlier version of the test which gave only one score.

Sternberg – triarchial model (cognitive perspective)

➢ Sternberg proposed that the cultural factors are also important in IQ testing as the skills
considered useful may not be useful in other cultures like verbal skills are considered
as marker of intelligence in western society but may not be in African society where
hunting skills are important
➢ He called these as Contextual subtheory
➢ He also gave other factors like Experiential subtheory and Componential subtheory
which along with the contextual subtheory forms intelligence
➢ His model is known as triarchial model
➢ He further divided componential subtheory into three components; metacomponents,
performance components, Knowledge and acquisition components

Gardon:
Gardon considered that most of the IQ tests have tapped only verbal and mathematical ability
and have neglected other areas. His theory states that there are 7 different dimensions in
intelligence and they may be different from each other. The 7 dimensions named by him are,
1. Logical –mathematics
2. Linguistics
3. Music
4. Spatial
5. Bodily-kinesthetic
6. Interpersonal
7. Intrapersonal

Reaction time
➢ Jensen and Eysenck have tried to discover the culture free intelligence and have
focused on the sensory processing similar to Galton

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➢ Jensen gave the concept of Reaction time which is the time taken by a subject to
respond to a particular stimulus. In his experiment subject was asked to press a
particular button when a particular color was displayed. The time lag was known as
reaction time and fairly correlated with the other measures of intelligence
➢ May be because IQ tests emphasize on speed with the notion that fast is the smart,
there is a correlation between reaction time and IQ tests. However other explanations
also cannot be ruled out.

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 Describe the stages of cognitive development as described by Jean
Piaget

Dr Amitkumar Chougule

Introduction:

➢ Jean Piaget (1896 to 1980) was, at various points in his career, considered to be a
natural scientist, psychologist, sociologist, and historian of the philosophy of science
➢ His major enterprise was what he termed “genetic epistemology,” the study of the
development of logic, reasoning, and higher-level thinking
➢ He designated himself a genetic epistemologist—one who studies the development of
knowledge from infancy to adolescence
➢ Piaget’s approach was, in his words, “constructivist structuralism,” according to which
mental structures are built through the interaction of the child and the world
➢ Jean Piagets theory:
“Biological maturation, learning, and social interaction flow together to facilitate
development and crystallize in the process of equilibration as the developing child
reacts to cognitive challenges generated by new input”

Stages of cognitive development by Jean Piaget:

1. Sensorimotor Period:

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 The sensorimotor period of intelligence is so named because the child’s construction
of mental schemata is in no way aided by representations, symbols, or thoughts.

Rather, schemata depend totally on perceptions and bodily movements

Stage 1 of sensorimotor development:

organized reflexes: sucking reflex and the palmar reflex

These primitive reflexes demonstrate three types of assimilation:

1. Reproductive
2. Generalizing
3. Recognitory
Stage 2: Contains the first habits and the primary circular reactions

stage 3: An initial distinction between means and ends becomes apparent, but in a
primitive sense

stages 4 and 5: Infants use a variety of means to obtain particular goals

During the sensorimotor period, a number of significant concepts are developed,

including the child’s concepts of space, time, and causality

SCHEMA OF OBJECT PERMANENCE:

The knowledge that objects in the external world have an existence independent of the
child’s actions on them or interactions with them is a major accomplishment of the
sensorimotor period

2. Preoperational Subperiod and Semiotic Function:

The advent of the preoperational subperiod is marked by the appearance of what

Piaget called the semiotic function

This new ability was defined by Piaget as follows:

“It consists in the ability to represent something (a signified object, event, conceptual
scheme, etc.) by means of a signifier which is differentiated and which serves only a
representative purpose like Language, mental image, symbolic gesture and so on.

CHARACTERISTIC BEHAVIOR PATTERNS:

The semiotic function is heralded by five characteristic behavior patterns in evidence

during the second year of life:

(1) Deferred imitation: According to Piaget, imitation is behavior in which “the subject’s
schemes of action are modified by the external world without his utilizing this external
world.” In imitation, the child’s cognitive structures undergo temporary change without
simultaneously incorporating new aliment

(2) Symbolic play, or the game of pretending

(3) Drawing, or the use of graphic imagery

(4) The presence of a mental image

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 (5) The verbal evocation of events not occurring at the time

3. Concrete Operations:

A crucial difference between preoperational and concrete-operational thought is the

presence within operative thinking of concepts of conservation

When concrete operations have been organized into a system, the child can conserve,
that is, “discover what values do remain invariant in the course of any given kind of
change or transformation.”

CONSERVATION OF QUANTITY:

➢ If liquid is poured from a short, wide glass into a tall, narrow one, the child in
the preoperational stage thinks that the amount of liquid has changed
➢ At the level of concrete operations, however, children are no longer
overwhelmed by the perceptual discrepancy between the two configurations
CONSERVATION OF WEIGHT AND VOLUME:

➢ At approximately 7 or 8 years of age, the child can solve the conservation-of-

quantity problem and can perform similar judgments of conservation when, for
example, a lump of clay is transformed in shape
➢ Between 9 and 10 years of age, the child discovers that the weight of a given
object is also conserved, even when its shape is transformed
➢ However, not until approximately 11 or 12 years of age do children have a
logical comprehension that the volume displaced by a given object is conserved
even after a transformation of the object’s shape
➢ Cardinal numbers
➢ Operations:
For Piaget, an operation is an action that is (1) interiorized, (2) reversible and
(3) part of an organized system of such actions
➢ Class inclusion:
The concrete operation of class inclusion underlies one’s ability to think
categorically
➢ RELATIONS:
The concrete operation that demonstrates an understanding of relations is
seriation
The concrete operation of seriation underlies one’s ability to think
dimensionally.
4. Formal Operations:

In the third and final stage in Piaget’s conception of the intellectual development in the
child, the logical structures of concrete operations are superseded by structures
referred to as formal operations

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 Three characteristics follow from this fundamental reorientation in thought:

(1) Adolescent thought is hypothetical-deductive

(2) It deals in propositions rather than in concrete events

(3) It can isolate variables and examine all possible combinations of variables

HYPOTHETICAL-DEDUCTIVE THOUGHT:

➢ As a hypothetical-deductive form of thought, formal operational intelligence

proceeds from the possible to the real
➢ It mirrors scientific reasoning
➢ The implications of a propositional statement are drawn and then tested against
reality
PROPOSITIONAL THOUGHT:

➢ That formal operations deal in propositions rather than in concrete events

implies increased freedom from immediate content
➢ This freedom implies:
1. The ability to manipulate abstractions that have been tied to concrete examples
or events
2. That the adolescent can abstract the results of that operation and can perform
further operations on them
ISOLATING VARIABLES AND EXAMINING COMBINATIONS:

➢ Instead of dealing with disparate concrete experiments, hypothetical-deductive

adolescents can organize their investigations into a coherent pattern from the
outset and then perform all relevant combinations of variables to test their
hypotheses, thus isolating causal factors
Criticism to Piagets theory:

Piaget’s theory focuses primarily on logical-deductive reasoning. Little attention is paid to

social intelligence, emotional intelligence, or alternative types of intelligence, such as artistic
or athletic intelligence.

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 Describe the stages of Psychosexual development as described by
Sigmund Freud

Dr Amitkumar Chougule

Introduction:

➢ The earliest manifestations of infantile sexuality arose in relation to bodily functions

that had been regarded as basically nonsexual, such as feeding and development of
bowel and bladder control
➢ But Freud saw that these functions involved degrees of sensual pleasure, which he
interpreted as forms of psychosexual stimulation, and divided them into a succession
of developmental phases, each of which was thought to build on and subsume
accomplishments of the preceding phases—namely the oral, anal, and phallic phases
➢ The oral phase occupied the first 12 to 18 months of the infant’s life; next came the
anal phase, lasting until about 3 years of age; and, finally, the phallic phase, from
approximately 3 to 5 years of age. Urethral, latency, and genital phases were added
to complete the picture.
➢ Freud’s basic schema of the psychosexual stages was modified and refined by Karl
Abraham, who further subdivided the phases of libido development, dividing the oral
period into a sucking and biting phase, and the anal phase into a destructive-expulsive
(anal sadistic) and a mastering-retaining (anal erotic) phase
Phases of Psychosexual Development

Oral Stage

Definition:

Earliest stage of development in which the infant’s needs, perceptions, and modes of
expression are primarily centered in mouth, lips, tongue, and other organs related to oral zone
and around the sucking reflex.

Description:

➢ Oral zone maintains dominance in psychic organization through approximately first 18

months of life
➢ Oral sensations include thirst, hunger, pleasurable tactile stimulations evoked by the
nipple or its substitute, sensations related to swallowing and satiation
➢ Oral drives consist of two components: Libidinal and aggressive
➢ States of oral tension lead to seeking for oral gratification, as in quiescence at the end
of nursing. Oral triad consists of wishes to eat, sleep, and reach that relaxation that
occurs at the end of sucking just before the onset of sleep.
➢ Libidinal needs (oral erotism) predominate in early oral phase, whereas they are mixed
with more aggressive components later (oral sadism)
➢ Oral aggression is expressed in biting, chewing, spitting, or crying
➢ Oral aggression is connected with primitive wishes and fantasies of biting, devouring,
and destroying.

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Objectives:

To establish a trusting dependence on nursing and sustaining objects, establish comfortable

expression and gratification of oral libidinal needs without excessive conflict or ambivalence
from oral sadistic wishes.

Pathological traits:

➢ Excessive oral gratifications or deprivation can result in libidinal fixations contributing

to pathological traits
➢ Such traits can include excessive optimism, narcissism, pessimism (as in depressive
states), or demandingness
➢ Envy and jealousy are often associated with oral traits
Character traits:

➢ Successful resolution of the oral phase results in capacities to give to and receive from
others without excessive dependence or envy, capacity to rely on others with a sense
of trust as well as with a sense of self-reliance and self-trust
➢ Oral characters are often excessively dependent and require others to give to them
and look after them, and are often extremely dependent on others for maintaining self-
esteem
➢ These are readily amalgamated with narcissistic needs

Anal Stage:

Definition:
The stage of psychosexual development promoted by maturation of neuromuscular
control over sphincters, particularly the anal sphincter, permitting greater voluntary
control over retention or expulsion of feces.
Description:
➢ This period extends roughly from 1 to 3 years of age, marked by recognizable
intensification of aggressive drives mixed with libidinal components in sadistic
impulses
➢ Acquisition of voluntary sphincter control is associated with an increasing shift
from passivity to activity
➢ Conflicts over anal control and struggles with parents over retaining or expelling
feces in toilet training give rise to increased ambivalence, together with conflicts
over separation, individuation, and independence
➢ Anal erotism refers to sexual pleasure in anal functioning, both in retaining
precious feces and presenting them as a precious gift to the parent
➢ Anal sadism refers to expression of aggressive wishes connected with
discharging feces as powerful and destructive weapons
➢ These wishes are often displayed in fantasies of bombing or explosions
Objectives:
➢ The anal period is marked by greater striving for independence and separation
from dependence on and control of parents
➢ Objectives of sphincter control without overcontrol (fecal retention) or loss of
control (messing) are matched by attempts to achieve autonomy and
independence without excessive shame or self-doubt from loss of control

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 Pathological traits:

➢ Maladaptive character traits, often apparently inconsistent, derive from

anal erotism and defenses against it
➢ Orderliness, obstinacy, stubbornness, willfulness, frugality, and
parsimony are features of anal character
➢ When defenses against anal traits are less effective, anal character
reveals traits of heightened ambivalence, lack of tidiness, messiness,
defiance, rage, an sadomasochistic tendencies
➢ Anal characteristics and defenses are typically seen in obsessive-
compulsive neuroses
Character traits:

Successful resolution of the anal phase provides the basis for development of:
1. Personal autonomy
2. Capacity for independence
3. Personal initiative without guilt
4. Capacity for self-determining behavior without a sense of shame or self-
doubt
5. Lack of ambivalence
6. Capacity for willing cooperation without either excessive willfulness or
self-diminution or defeat
Urethral Stage:

Definition:

This stage was not explicitly treated by Freud but serves as a transitional stage between anal
and phallic stages. It shares some characteristics of anal phase and some from subsequent
phallic phase.

Description:

➢ Characteristics of the urethral phase are often subsumed under phallic phase
➢ Urethral erotism, however, refers to pleasure in urination as well as pleasure in urethral
retention analogous to anal retention
➢ Similar issues of performance and control are related to urethral functioning
➢ Urethral functioning may also have sadistic quality, often reflecting persistence of anal
sadistic urges
➢ Loss of urethral control, as in enuresis, may frequently have regressive significance
that reactivates anal conflicts
Objectives:

➢ At stake are issues of control and urethral performance and loss of control
➢ It is not clear whether or to what extent objectives of urethral functioning differ from
those of anal period, except that they are expressed in a later developmental stage
Pathological traits:

➢ The predominant urethral trait is competitiveness and ambition, probably related to

compensation for shame due to loss of urethral control
➢ This may instigate development of penis envy, related to feminine sense of shame and
inadequacy in being unable to match male urethral performance

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 ➢ This may also be related to issues of control and shaming

Character traits:

➢ Besides healthy effects analogous to those from the anal period, urethral competence
provides a sense of pride and self-competence based on performance
➢ Urethral performance is an area in which the small boy can imitate and try to match his
father’s more adult performance
➢ Resolution of urethral conflicts sets the stage for budding gender identity and
subsequent identifications
Phallic Stage:

Definition:

Phallic stage begins sometime during third year and continues until approximately end of fifth
year

Description:

➢ The phallic phase is characterized by a primary focusing of sexual interests,

stimulation, and excitement in the genital area
➢ The penis becomes the organ of principal interest to children of both sexes, with lack
of penis in females being considered as evidence of castration
➢ The phallic phase is associated with an increase in genital masturbation accompanied
by predominantly unconscious fantasies of sexual involvement with the opposite-sex
parent
➢ Threats of castration and the related anxiety are connected with guilt over masturbation
and oedipal wishes
➢ During this phase oedipal involvement and conflict are established and consolidated
➢ Oedipus (in males) /Electra (in females) complex: attraction to opposite-sex parent;
rivalry with same-sex parent
Objectives:

➢ To focus erotic interest in genital area and genital functions

➢ This lays the foundation for gender identity and serves to integrate residues of previous
stages into a predominantly genital-sexual orientation
Pathological traits:

➢ Derivation of pathological traits from phallic-oedipal involvement is sufficiently complex

and subject to such a variety of modifications that it encompasses nearly the whole of
neurotic development
➢ Issues, however, focus on castration in males and penis envy in females
➢ Patterns of internalization developed from resolution of the Oedipus complex provide
another important focus of developmental distortions
➢ The influence of castration anxiety and penis envy, defenses against them, and
patterns of identification are primary determinants of the development of human
character
➢ They also subsume and integrate residues of previous psychosexual stages, so that
fixations or conflicts deriving from preceding stages can contaminate and modify
oedipal resolution

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Character traits:

The phallic stage provides the foundations for:

1. An emerging sense of sexual identity

2. Sense of curiosity without embarrassment
3. Initiative without guilt
4. Sense of mastery not only over objects and persons in the environment but also over
internal processes and impulses
Resolution of the oedipal conflict gives rise to internal structural capacities for regulation of
drive impulses and their direction to constructive ends

The internal sources of such regulation are the ego and superego, based on introjections and
identifications derived primarily from parental figures

Latency Stage

Definition:

This is the stage of relative instinctual quiescence or inactivity of sexual drive during the period
from the resolution of the Oedipus complex until pubescence (from about 5–6 years until about
11–13 years)

Description:

➢ The institution of the superego at the close of the oedipal period and further maturation
of ego functions allow for considerably greater degrees of control of instinctual
impulses and motives
➢ This is a period of primarily homosexual affiliations for both boys and girls, as well as
a sublimation of libidinal and aggressive energies into energetic learning and play
activities, exploring the environment, and becoming more proficient in dealing with the
world of things and persons around them
➢ It is a period for development of important skills
➢ The relative strength of regulatory elements often gives rise to patterns of behavior
that are somewhat obsessive and hypercontrolling
➢ Relative quiescence of libidinal drives
➢ Sexual drives channelled into socially appropriate activities (e.g., school work, sports)
➢ Further development of ego functions (judgment, frustration tolerance etc.)
➢ Formation of superego (conscience)
Objectives:

➢ The primary objective is further integration of oedipal identifications and consolidation

of gender and sex-role identity
➢ Relative quiescence and control of instinctual impulses allow for development of ego
apparatuses and mastery of skills

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 ➢ Further identificatory components may be added to the oedipal ones on the basis of
broadening contacts with other significant figures outside the family, e.g., teachers,
coaches, and other adult figures.

Pathological traits:

➢ Dangers in the latency period can arise either from the lack of development of inner
controls or an excess of them
➢ Lack of control can lead to failure to sufficiently sublimate energies in the interest of
learning and the development of skills
➢ an excess of inner control, however, can lead to premature closure of personality
development and precocious elaboration of obsessive character traits
Character traits:

➢ The latency period is frequently regarded as a period of relatively unimportant inactivity

in the developmental schema
➢ More recently, greater respect has been gained for the developmental processes in
this period
➢ Important consolidations and additions are made to basic postoedipal identifications
and to processes of integrating and consolidating previous attainments in
psychosexual development and establishing decisive patterns of adaptive functioning
➢ The child can develop a sense of industry and capacity for mastery of objects and
concepts that allows autonomous functioning and a sense of initiative without risk of
failure or defeat or a sense of inferiority
➢ These are all important attainments that need to be further integrated, ultimately as the
essential basis for a mature adult life of satisfaction in work and love

Genital Stage:

Definition:

The genital or adolescent phase extends from the onset of puberty from approximately
ages 11–13 until young adulthood

Current thinking tends to subdivide this stage into preadolescent, early adolescent, middle
adolescent, late adolescent, and even postadolescent periods

Description:

➢ Physiological maturation of systems of genital (sexual) functioning and attendant

hormonal systems leads to intensification of instinctual, particularly libidinal drives
➢ This produces a regression in personality organization, which reopens conflicts of
previous stages of psychosexual development and provides opportunity for
resolution of these conflicts in the context of achieving a mature sexual and adult
identity. This period has been described as a “second individuation.”

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Objectives:

➢ Primary objectives are the ultimate separation from dependence on and

attachment to parents and establishment of mature, nonincestuous, heterosexual
object relations
➢ Related are the achievement of a mature sense of personal identity and
acceptance and integration of adult roles and functions that permit new adaptive
integrations with social expectations and cultural values.
Pathological traits:

➢ Pathological deviations due to failure to achieve successful resolution of this stage

of development are multiple and complex
➢ Defects can arise from a whole spectrum of psychosexual residues, since the
developmental task of adolescence is in a sense a partial reopening and reworking
and reintegrating of all of these aspects of development
➢ Previous unsuccessful resolutions and fixations in various phases or aspects of
psychosexual development will produce pathological defects in the emerging adult
personality and defects in identity formation
Character traits:

➢ Successful resolution and reintegration of previous psychosexual stages in the

adolescent genital phase set the stage normally for a fully mature personality with
the capacity for full and satisfying genital potency and a self-integrated and
consistent sense of identity
➢ This provides the basis for a capacity for self-realization and meaningful
participation in areas of work, love, and in creative and productive application to
satisfying and meaningful goals and values

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 Stress-Diathesis model

Dr Amitkumar Chougule

Introduction:

Schematic of diathesis–stress model.

➢ The diathesis–stress model is a psychological theory that attempts to explain

behavior as a predispositional vulnerability together with stress from life experiences
➢ The term diathesis derives from the Greek term for disposition, or vulnerability, and it
can take the form of genetic, psychological, biological, or situational factors
➢ A large range of individual differences exist between persons in their vulnerability to
the development of disorder
➢ Stress refers to a life event or series of events that disrupt a person’s psychological
equilibrium and potentially serves as a catalyst to the development of a disorder

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 ➢ Thus, the diathesis–stress model serves to explore how biological or genetic traits
(diatheses) interact with environmental influences (stressors) to produce disorders,
such as depression, anxiety, or schizophrenia.
➢ The diathesis–stress model asserts that if the combination of the predisposition and
the stress exceeds a threshold, the person will develop a disorder.
➢ The use of term diathesis in the fields of medicine and psychiatry dates back to the
1800s; however, the diathesis–stress model was not introduced and utilized to
describe the development of psychopathology until it was used to
explain schizophrenia in the 1960s.
➢
The diathesis–stress model is used in many fields of psychology, specifically for
studying the development of psychopathology. It is useful for the purposes of
understanding the interplay of nature and nurture in the susceptibility to psychological
disorders throughout the lifespan.
➢ Diathesis–stress models can also assist in determining who will develop a disorder
and who will not. For example, in the context of depression, the diathesis–stress model
can help explain why Person A may become depressed while Person B does not, even
when exposed to the same stressors.
➢ More recently, the diathesis–stress model has been used to explain why some
individuals are more at risk for developing a disorder than others. For example, children
who have a family history of depression are generally more vulnerable to developing
a depressive disorder themselves
➢ A child who has a family history of depression and who has been exposed to a
particular stressor, such as exclusion or rejection by his or her peers, would be more
likely to develop depression than a child with a family history of depression that has an
otherwise positive social network of peers
➢ The diathesis–stress model has also served as useful in explaining other poor (but
non-clinical) developmental outcomes
➢ Protective factors, such as positive social networks or high self-esteem, can counteract
the effects of stressors and prevent or curb the effects of disorder
➢ Many psychological disorders have a window of vulnerability, during which time an
individual is more likely to develop disorder than others
➢ Diathesis–stress models are often conceptualized as multi-causal developmental
models, which propose that multiple risk factors over the course of development
interact with stressors and protective factors contributing to normal development or
psychopathology
➢ The differential susceptibility hypothesis is a recent theory that has stemmed from the
diathesis–stress model
Diathesis:

➢ The term diathesis is synonymous with vulnerability

➢ Vulnerability makes it more or less likely that an individual will succumb to the
development of psychopathology if a certain stress is encountered
➢ Diatheses are considered inherent within the individual and are typically
conceptualized as being stable, but not unchangeable, over the lifespan
➢ They are also often considered latent (i.e. dormant), because they are harder to
recognize unless provoked by stressors

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 ➢ It includes genetic, biological, physiological, cognitive and personality-related factors.
Some examples of diatheses include genetic factors, such as abnormalities in some
genes or variations in multiple genes that interact to increase vulnerability
➢ Other diatheses include early life experiences such as the loss of a parent or high
neuroticism
➢ Diatheses can also be conceptualized as situational factors, such as low socio-
economic status or having a parent with depression
Stress:

➢ Stress can be conceptualized as a life event that disrupts the equilibrium of a person’s
life. For instance, a person may be vulnerable to become depressed, but will not
develop depression unless he or she is exposed to a specific stress, which may trigger
a depressive disorder
➢ Stressors can take the form of a discrete event, such the divorce of parents or
a death in the family, or can be more chronic factors such as having a long-term illness,
or ongoing marital problems
➢ Stresses can also be related to more daily hassles such as school assignment
deadlines.
➢ It has been long recognized that stress plays a significant role in understanding how
psychopathology develops in individuals
➢ However, psychologists have also identified that not all individuals who are stressed,
or go through stressful life events, develop a psychological disorder
➢ To understand this, theorists and researchers explored other factors that affect the
development of a disorder and proposed that some individuals under stress develop a
disorder and others do not
➢ As such, some individuals are more vulnerable than others to develop a disorder once
stress has been introduced. This led to the formulation of the diathesis–stress model.
Protective factors:

➢ Protective factors, while not an inherent component of the diathesis–stress model, are
of importance when considering the interaction of diatheses and stress
➢ Protective factors can mitigate or provide a buffer against the effects of major stressors
by providing an individual with developmentally adaptive outlets to deal with stress
➢ Examples of protective factors include a positive parent-child attachment relationship,
a supportive peer network, and individual social and emotional competence
➢ Many models of psychopathology generally suggest that all people have some level of
vulnerability towards certain mental disorders, but posit a large range of individual
differences in the point at which a person will develop a certain disorder.
➢ For example, an individual with personality traits that tend to promote relationships
such as extroversion and agreeableness may engender strong social support, which
may later serve as a protective factor when experiencing stressors or losses that may
delay or prevent the development of depression
➢ Conversely, an individual who finds it difficult to develop and maintain supportive
relationships may be more vulnerable to developing depression following a job loss
because they do not have protective social support
➢ An individual’s threshold is determined by the interaction of diatheses and stress.

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 ➢ Windows of vulnerability for developing specific psychopathologies are believed to
exist at different points of the lifespan. Moreover, different diatheses and stressors are
implicated in different disorders
➢ For example, breakups and other severe or traumatic life stressors are implicated in
the development of depression
➢ Stressful events can also trigger the manic phase of bipolar disorder and stressful
events can then prevent recovery and trigger relapse
➢ Having a genetic disposition for becoming addicted and later engaging in binge
drinking in college are implicated in the development of alcoholism
➢ A family history of schizophrenia combined with the stressor of being raised in a
dysfunctional family raises the risk of developing schizophrenia
➢ Diathesis–stress models are often conceptualized as multi-causal developmental
models, which propose that multiple risk factors over the course of development
interact with stressors and protective factors contributing to normal development or
psychopathology. For example, a child with a family history of depression likely has a
genetic vulnerability to depressive disorder
➢ This child has also been exposed to environmental factors associated with parental
depression that increase his or her vulnerability to developing depression as well.
Protective factors, such as strong peer network, involvement in extracurricular
activities, and a positive relationship with the non-depressed parent, interact with the
child’s vulnerabilities in determining the progression to psychopathology versus
normative development.
➢ Some theories have branched from the diathesis–stress model, such as the differential
susceptibility hypothesis, which extends the model to include a vulnerability to positive
environments as well as negative environments or stress. A person could have a
biological vulnerability that when combined with a stressor could lead to
psychopathology (diathesis – stress model); but that same person with a biological
vulnerability, if exposed to a particularly positive environment, could have better
outcomes than a person without the vulnerability.
Types of Stress Diathesis models:

1. Additivity
On the surface, diathesis-stress models represent straightforward, linear, dose
response– type relationships, or additive relationships.
2. Ipsative Models
Ipsative models posit an inverse relationship between factors such that the
greater the presence of one factor, the less of the other factor is needed to
bring about the disorder.
3. Static Versus Dynamic Diathesis-Stress Relationships
4. Interactive Model With Dichotomous Diatheses
5. Quasi-Continuous Diathesis Models
6. Threshold Models
7. Risk-Resilience Continuum Models

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 hat is structured clinical assessment? name some structured
clinical instruments used in epidemiological studies. discuss
advantages and disadvantages of this approach in Psychiatry

Dr Amitkumar Chougule

Background:

Reasons for the development of structured clinical assessment or interviewing and

rating instruments:

1. For research purposes, it was necessary to demonstrate overtly that the

essential topics have been covered in a comprehensive and systematic
manner during an interview
2. To avoid examiner/ clinician bias
3. For purpose of communication between researchers in different institutes
4. For good inter-rater reliability
Structured clinical assessment instruments:

The instruments now available can be grouped according to the main purposes for
which they were designed

Instruments for the assessment of mental state and behaviour

GHQ:

1. Screening instruments such as the General Health Questionnaire are needed

for the identification of likely cases or high-risk individuals amongst large
populations
2. These tend to be short and economical in use, since they have to be
administered to large numbers of subjects
3. This is essential for screening and for epidemiological studies, but this single
score does not convey much about the details of the subject's feelings or
behaviour, and so is of limited interest to the clinician
Detailed instruments may contain the following:

1. Symptoms of only one type:

➢ Hamilton's rating scale for depression (HAM-D)
➢ Scale for Assessment of Negative Symptoms (SANS)

527
2. A selection of symptoms for the study of the relationships between two closely related
types, such as depressive and schizophrenic symptoms in the Schedule for Affective
Disorders and Schizophrenia
3. A limited number of items covering different symptoms and behaviour selected as
being of special importance, as in the recently developed Health of the Nation Scales
of the United Kingdom
4. A more or less comprehensive array of symptoms that allows the study of the relative
distribution of symptoms of many different types, such as:
➢ Schedules for Clinical Assessment in Neuropsychiatry(SCAN)
➢ Composite International Diagnostic Interview(CIDI)
widely used but less tightly structured instruments with a comprehensive content are:
➢ Brief Psychiatric Rating Scale(BPRS)
➢ Composite Psychopathological Rating Scale
The structured clinical assessment used in epidemiological studies:

1.The Present State Examination:

➢ The Present State Examination (PSE) is a semi-structured procedure, based

upon an interview schedule containing items that are rated as the interview
proceeds
➢ The content of the PSE has always been more or less comprehensive, and it
contains a number of symptoms, such as worry, muscular tension,
restlessness, etc., that are not associated with particular diagnoses
➢ These symptoms are included because they are often clinically obvious and
also important to the patient
2. Schedule for Affective Disorders and Schizophrenia, and the Structured
Clinical Interview for DSM

➢ The series of instruments developed by Spitzer and his colleagues at

Biometrics of the New York State Psychiatric Institute have been of several
different kinds and, in the early years at least, had a much more rigid
structure than the PSE
➢ Users of the Mental Status Schedule and the longer Psychiatric Status
Schedule were instructed to follow the order of the questions as printed in
the schedule, the only deviation from this being a repetition of the same
questions if thought necessary by the interviewer
➢ However, later instruments such as the Schedule for Affective Disorders
and Schizophrenia and, more recently, the Structured Clinical Interview for
DSM-III and DSM-IV, DSM-5, allow more flexibility for the interviewer in
both interview style and the choice of a little or a lot of training
➢ despite its length, the Structured Clinical Interview for DSM is
recommended for clinical use as well as for research
➢ There has also been an increasing tendency for instruments from the New
York group to be dedicated to a particular purpose. For instance, the
content of the Schedule for Affective Disorders and Schizophrenia is keyed
towards the study of relationships between schizophrenia and affective
disorders, and the Structured Clinical Interview for DSM contains only those
items that are necessary for identifying disorders present in the
corresponding DSM

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 3. The Diagnostic Interview Schedule:

➢ The third major research group is based at Washington University, St Louis,

Missouri, and is well known as the originator of the first widely used sets of
Diagnostic Criteria for Research
➢ Following the publication of DSM-III in 1980, there was considerable interest in
discovering how the disorders it contained were distributed in the American
population
➢ Supported by the National Institute of Mental Health, Lee Robins and her
colleagues designed the Diagnostic Interview Schedule (DIS) for this purpose
➢ This is composed of questions covering the symptoms required to identify what
were considered to be the 15 most important disorders in DSM-III
➢ The Epidemiological Catchment Area study of the National Institute of Mental
Health, the very large study in which the DIS was first used, included a
population sample of more than 18 000 subjects in five largely urban areas
4. Schedules of Clinical Assessment for Neuropsychiatry and the Composite
International Diagnostic Interview

➢ Although originating from different groups with different traditions and

purposes, the PSE and the DIS have now given rise to direct descendants,
namely the Schedules of Clinical Assessment for Neuropsychiatry (SCAN) and
the Composite International Diagnostic Interview (CIDI), that are closely
connected
➢ During the early 1980s, a collaborative programme of work between WHO and
the National Institute of Mental Health of the United States (known as the Joint
Project) resulted in the transformation of DIS into CIDI by increasing its
contents by adding large parts of first DSM-IIIR and then of the drafts of ICD-
10 and DSM-IV
➢ This was matched by the evolution of PSE-9 into PSE-10, the centrepiece of
SCAN whose content similarly covers almost all of both ICD-10 and DSM-IV
➢ The only sections of ICD-10 and DSM-IV not now covered by SCAN and CIDI
are those dealing with disorders of adult personality, disorders of childhood and
adolescence, and mental retardation
➢ The co-ordination by WHO of the development of the final stages of SCAN and
CIDI has been aimed at the production of two instruments with different but
complementary uses in epidemiological studies
➢ CIDI can be administered to comparatively large numbers of subjects in the
community since the use of lay interviewers keeps costs to a minimum
➢ SCAN is more suitable for the professional assessment of subjects with
obvious or severe disorders
Miscellaneous instruments:

1. Scale for assessment of negative symptoms

2. Psychological impairment rating scale
3. International personality disorder examination (IPDE)

Reference:

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The New Oxford Textbook Of Psychiatry

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