 SCHIZOPHRENIA

 The DSM-5 defines schizophrenia as a severe mental disorder

characterized by disturbances in thinking, emotion, and behaviour.
 It includes symptoms such as hallucinations, delusions, disorganised
thinking, disorganised or abnormal motor behaviour, and negative
symptoms. These symptoms must be present for a significant portion of
time during one month, with impairments in social or occupational
functioning lasting for at least six months.

 The word or term "Schizophrenia" comes from the Greek word skhizein
meaning "to split '' and the Greek word 'phrene' (phrone) - meaning
'diaphragm, heart. mind'. Schizophrenia is a psychotic disorder in which
the term means 'split mind' (this split does not refer to splitting of
personality as in multiple personality disorder), this is because there is a
split between emotion and cognition. Schizophrenia is not a single
disorder but a syndrome consisting of several different types of disorders.
However, DSM-4 treats it as a single entity. This term was coined by "the
famous Swiss psychiatrist ‘Eugen Bleuler' (1857- 1939), In the year 1911
it was accepted later worldwide it denotes a severe uncomplex mental
illness where the patient loses the ability to think, feel or
 behave in a normal way. The patient perceives a distorted reality but is
usually unaware that he/she is ill.

 Patients also suffer from delusions that are firmly held but false beliefs &
begin to act on them as a result of their faulty thinking and perception
their behaviour becomes abnormal.
 Nearly 6-7 Million Indians suffer from this disorder variously described
as the 'cancer of the mind' & the ' greatest disorder of the youth'. It starts
in the most productive period of life (15-45 years) and is cosmopolitan in
its occurrence. It is now widely recognized that schizophrenia is a brain
disorder. The DSM-4 of the American Psychiatric Association defines
schizophrenia as a clinical mental disorder. The 17th edition of Meek's
defines schizophrenia as follows 'a common and serious mental disorder
characterised by loss of contact with reality, delusions, abnormal
thinking, flattened affect, diminished motivation and disturbed work and
social functioning ". The National Institute of Mental Health wrote in
 2010 " Schizophrenics may hear voices other people don't hear, they may
believe other people are reading their minds, controlling their thoughts,
plotting to harm them. This can terrify people with the illness and make
them withdrawn or extremely agitated". People with schizophrenia may
not make sense when they talk, they may sit for hours without moving or
talking, and sometimes people with schizophrenia seem perfectly fine
until they talk about what they are thinking.

 SCHIZOPHRENIA: the origin of the construct

 Historical antecedents of the constructs of schizophrenia
 History - how the term was coined
 What were the developments that took place

 EPIDEMIOLOGY - is the study of the distribution or prevalence of

diseases, disorders or health-related behaviours in a given situation.

 One out of every 140 alive today who survive until at least age 55 will
develop the disorder.
 Some people (for example, those who have a parent with schizophrenia)
have a statistically higher risk of developing the disorder than others.
 other groups of people seem to have an especially high risk of developing
schizophrenia. For example, people whose fathers were older (aged 45 to
50 years or more) at the time of their birth have 2 to 3 times the normal
risk of developing schizophrenia when they grow up (Byrne et al. 2003).
 The vast majority of cases of schizophrenia began in late adolescence and
early adulthood with 18 to 30 years of age being the peak time for the
onset of the illness (Tandon et al 2009)
 Interesting schizophrenia tends to begin earlier in men (20 to 24 years of
age) than in women (35 to 45 years of age) because of the protected
effects of estrogenic present in women.
 In addition to having an earlier age of onset, Males also tend to have a
more severe form of schizophrenia brain imaging studies show that
schizophrenia related abnormalities of brain structure are more severe in
male patients than they are in female patients.
 One particularly stable finding often referred to as urban drift, has been
the association between living in an urban environment and diagnosis of
schizophrenia.
 It is prevalent in all cultures: similar incidents across continents.

 CLINICAL PICTURE: SIGNS AND SYMPTOMS

 The symptoms of schizophrenia fall into 3 categories (can, co-occur in the

same patient):
 Positive Symptoms
 Negative Symptoms
 Disorganised Symptoms (Lanzinger et al. 1991)

 Two general symptom patterns or syndromes of schizophrenia have been

differentiated: these are called positive and negative symptoms of
schizophrenia (Andreasen et al. 1995).

 Positive Symptoms - signs and symptoms in which something has been

added to the normal repertoire of the behaviour and experience (an excess
in a normal repertoire of behaviour and experience). Presence of
Characteristics Psychotic Symptoms (hallucinations and delusions). It
responds to treatment much more than negative symptoms.

 Disturbance of thought content: Delusions

 Psychiatrist and philosopher Karl Jaspers was the first to define the three
main criteria for a belief to be considered delusional in his 1913 book
"General Psychopathology" These criteria are: certainty (held with
absolute conviction), incorrigibility (not changeable by compelling
counterargument or proof to the contrary), impossibility or falsity of
content (implausible, bizarre or patently untrue)

 A delusion is essentially an erroneous belief that is fixed and firmly held

despite clear contradictory evidence. The word delusion comes from the
Latin verb ludre which means "to play " in essence tricks up the mind.
People with delusions believe things that others who share their social,
religious and cultural backgrounds do not believe. A delusion therefore
 involves a disturbance in the content of thought. Not all people who have
delusions suffer from schizophrenia. However, delusions are common in
schizophrenia occurring in more than 90% of patients at some time during
their illness (Cutting, 1995).
 In DSM-4, a delusion is defined as: a false belief based about external
reality that is firmly sustained despite evidence to the contrary. The belief
is not one ordinarily accepted by other members of the person's culture.
 Because of its importance in schizophrenia, delusion has been called "the
basic characteristic of madness' (Jaspers, 1963).
 Disturbances in thought usually involve certain types of delusions or false
beliefs:
 Delusion of Persecution - "out to get me"
 Delusion of Control (someone is controlling the thought) - " Neighbour
is an alien and has the power to control my thinking for evil purposes"
 Types of delusion of control
 Thoughts broadcasting (false belief that the affected person's thoughts are
heard aloud),
 Thoughts insertion (a false belief that thoughts are being inserted into
one’s brain by some external agency.
 Thought withdrawal (a false belief that an outside force or person is
extracting or removing one's thoughts).

 Delusion of Reference - "talking about me" (where some neutral

environmental event such as a TV programme or a song on the radio is
believed to have special and personal meaning intended only for the
person)
 Delusions of Grandeur - A person with the delusion of grandeur would
believe that he is famous and important (such as believing that one is
Jesus Christ or Mother Teresa) and he would be trying to "save the
world".
 Nihilistic delusion - the belief that something does not exist (one’s brain,
a part of the world).
 Delusion of Jealousy - delusion that the individual's sexual partner is
unfaithful (morbid jealousy or Othello syndrome)
 Somatic delusion - usually the false belief is that the body is somehow
diseased, abnormal or changed. An example of a somatic delusion would
be a person who believes that his/her body is infected with parasites.
 Erotomaniac delusion - a person beliefs that another person, often
someone important or famous is in love with him/her.

 DISRUPTION OF PERCEPTION: HALLUCINATIONS, ETC.

 The word comes from the Latin verb hallucinere or allucinere, meaning
to “wander in mind” or “idle talk.” (Aleman and Laroi 2008).

 A hallucination is a sensory experience that seems real to the person

having it, but occurs in the absence of any external perceptual stimulus.
This is quite different from an illusion, which is a misperception of a
stimulus that actually
 exists.

 Types of hallucinations-

 Auditory- hearing voices when there is no auditory stimulus The voice

may be heard either inside or outside one's head and is generally
considered more severe when coming from outside one's head. The voices
may be male or female, recognized as the voice of someone familiar or
not recognized as familiar and maybe critical or positive.

 Sometimes the voices consist of hearing a 'running commentary ‘on the

person's behaviour as it occurs (egg- she is taking a shower). Other times
the voices may tell the person to do something (commonly referred to as
command hallucinations).

 2. Gustatory- a false perception of taste: tasting sensations when there is

no stimulus for them. Usually, the experience is unpleasant for instance
an individual may complain of a persistent taste of metal. This type of
hallucination is more commonly seen in some medical disorders
(epilepsy) than in mental disorders.

 3. Olfactory- a false perception of odour or smell: smelling odour that is

not present. Typically, the experience is very unpleasant. For egg- the
 person may smell decaying fish, dead bodies or burning rubber.
Sometimes those experiencing olfactory hallucinations believe the odour
emanates from within.

 4. Somatic (inside one's body) or tactile (outside of one's body)- bugs are
crawling up one's back:
 A false perception or sensation of touch or something happening in or on
the body; feeling sensations when there is no stimulus for them. A
common tactile hallucination is feeling like something is crawling under
or on the skin (also known as formication).

 5. Visual hallucinations- a false perception of sight: seeing objects that

are not present.
 The content of the hallucinations may be anything (such as shapes, colour
and flashes of light) but are typically human-like figures. For e.g. - one
may perceive a person standing before them when no one is present.

 Negative symptoms -, refer to an absence or deficiency of behaviours

normally present in a person's repertoire, difficult to treat (All A's and
catatonia/immobility). However, not all negative symptoms may lack
emotions. In a study by Kranj & Neale 1996 it was found that patients
with schizophrenia may not look emotionally expressive but may be
internally experiencing plenty of emotions (as measured by autonomic
arousal. Patients with negative symptoms need help with everyday tasks.

 A's
 Alogia (poverty of speech) - absence or little speech. For example, if you
ask the person with alogia to describe a happy life experience the person
might respond 'getting married' and then fail to elaborate even when
asked for additional information.
 Anhedonia (absence of pleasure from life) - Anhedonia is the decreased
ability to experience pleasure. Individuals with schizophrenia can still
enjoy a pleasurable activity in the moment and can recall it, but show a
reduction in the frequency of engaging in pleasurable activity. People
with schizophrenia appear to have a deficit in anticipatory pleasure and
not consummatory pleasure (Gard et al. 2007).
 Apathy - feelings of indifference towards people, activities and events.
Many people with schizophrenia express little interest in the events.

 A - Affective blunting (emotional Flattening) - restricted range of

emotions. The person's face may remain immobile most of the time, no
matter what happens and body language may be unresponsive to what is
going on in the environment. For example, one man set fire to his house,
then sat down to watch TV when it was called to his attention that his
house was on fire, he calmly got up and walked outside (Torrey, 1995).
People with blunted affect may speak in a monotone voice without any
emotional expression and maybe make eye contact with others.
 A - Asociality refers to the apparent lack of interest in social interactions
and may be associated with avolition, but it can also be a manifestation of
limited opportunities for social interactions

 Disorganised symptoms (bizarre behaviour, disorganised speech

recognised by Legendary and 1991)
 Examples are as follows:
 Echopraxia - imitation of the movements of another person.
 Flight of ideas - continuous flow of verbalisation in which the person
jumps rapidly from one topic to another.
 Perseveration - Persistent adherence to a single idea or topic, verbal
repetition of sentence, word or phrase, resisting attempts to change the
topic.
 Ambivalence - Holding seemingly contradictory beliefs or feelings about
the same person, events or situation.
 Associative looseness - Fragmented or poorly related thoughts and ideas.
 Echolalia - imitating speech sounds of other people.

 Disorganised speech - is the external manifestation of a disorder in

thought form. An affected person fails to make sense despite seeming to
conform to the semantic and syntactic rules governing verbal
communication.

 Following are some of the indicators of disordered thinking which are

expressed in disorganised speech:
 Cognitive slippage or derailment: Mehul 1962, refers to this process as
"cognitive slippage" Which involves rapidly shifting from topic to topic,
making it very difficult to follow the conversation.

 Tangentiality - replying to questions in an irrelevant manner and never

reaching the goal. However, there is a clear association between sentences
(but the end is not reached). For example, the Mental Health professional
asks "What city are you from? " The answer is " Well that's a hard
question I don't know where my relatives came from so, I don't know if
I'm Irish or French "
 Word salad (or incoherence) - is at the end of the scale, the words are just
random words. For example - blue afraid you know carpet cat.

 Neologisms - new word formations. For example, I got so angry I picked

up a dish and threw it at the essence (a word used for gloves for hand
shoes)

 Echolalia - echoing other people's speech. For example, the mental health
professional is saying " Can we talk for minutes? " The patient replies, "
Talk for a few minutes, talk for a few minutes' '.

 blocking- the patient stops speaking and after seconds indicates he/she is
unable to remember what he/she had intended to say. Blocking may give
rise to the delusion that thoughts have been withdrawn from the head
o (Thought withdrawal).

 Neutisim - refusal or inability to speak.

 6. Flight of ideas - rapidly shifting from one topic to another which are
related by superficial associations. In its extreme forms, it involves
cognitive incoherence and disorganisation. For example, the mental
health professional is saying "How are you sleeping at night? " The
patient replied " Why would I sleep tonight; would you be able to do my
work? I whistle while I play and I am happy to do it all okay so that is
like a haul ".
  Disorganised behaviour - In disorganised behaviour, people lose their
ability to organise their behaviour to make it conform to social standards.
For instance, they may get into unreasonable bouts of agitation, dress in
unusual clothes, mutter to themselves, act childlike in a silly manner,
speak to themselves, and hoard food or garbage

Catatonia A striking example of disorganised behaviour is catatonia or the

motor dysfunctions that range from wild agitation to immobility. On one end
of the catatonic spectrum, some people may become extremely agitated, pace
rapidly, or move their fingers in a stereotyped way. On the other hand,
patients with catatonia may show almost an absence of movement and
speech. The person may appear to be completely unaware of the
surroundings. For instance, the person may hold an unusual posture for a
long period without any seeming discomfort.

ETIOLOGY (Causal factors)

 BIOLOGICAL FACTORS (family, twin & adoption studies)

Given the similarity in the symptoms and prevalence of schizophrenia
across cultures and across time. It is not surprising that biological factors
have long been thought to play a strong role in the development of
schizophrenia.

o Genetic factors: it has long been known that disorders of the

schizophrenic type are "familial" and tend to "run in families".
There is overwhelming evidence of higher-than-expected rates of
schizophrenia among biological relatives of index cases that is the
diagnosed group of people who provide the starting point for
inquiry also called probands. There is a strong association between
the closeness of the blood relationship (I.e. level of genes sharing)
and the risk for developing the disorder. For example, the
prevalence of schizophrenia in the first degree relatives (parents,
siblings and offspring) of a proband with schizophrenia is about
10% . For second degree relatives, who share only 25% of their
genes, with the proband, the lifetime prevalence of schizophrenia is
closer to 3%.
 Of course, just because something runs in families does not automatically
implicate genetic factors. The terms familial and genetic are not
synonymous and a disorder can run in a family for non-genetic reasons.
The interpretation of familial concordance patterns is not completely
straightforward in part because of the strong relationship between the
sharing of genes and the sharing of the environments in which those
genes express themselves. Family studies cannot by themselves tell us
why a disorder runs in a family. To this entangle the contribution of genes
and environment we need twin and adoption studies.
 Family studies : human genome project has discovered several genetic
linkages behind the causal factors of the disease. Genetic factors are
proposed to be responsible for the familial predesposition pf
schizophrenia ( more than 80%. Studies indicate that the disorder tends to
run in families giving rise to the notion of a "tainted gene". The
possibility of developing schizophrenia in the offspring is approximately
25-50% when the mother is schizophrenic.
 The disorder is now understood as the result of multiple genes and their
interaction. Specific genes appear to make only minor contributions
towards the illness ( William Son, 2007). Furthermore, patients who have
schizophrenia in their family histories have more negative symptoms than
those whose families are free of schizophrenia ( Malaspina et al, 2000)
suggesting that negative symptoms may have stronger genetic
components. According to a review of family studies a person with the
first degree relative with schizophrenia is almost 10 times more likely to
develop schizophrenia than a person with no schizophrenia in the
immediate family ( Schneider & Deldin, 2001).

 TWIN STUDIES

 Schizophrenia concordance rates ( correlation) for identical twins are

routinely and consistently found to be significantly higher than those of
fraternal twins or ordinary siblings. The most famous case of concordance
of schizophrenia is the dhet genain quadruplets. (Read this case) but the
specific symptoms, onset, course, and outcomes of the disorder varies
substantially among them ( Mirsky et al, 2000).
 Although being a twin does not increase one's risk for developing
schizophrenia study after study has shown a higher concordance for
schizophrenia among identical or monozygotic twins than among people
related in any other way, including fraternal or dizygotic twins.

 Torrey is a noted schizophrenia researcher who has a sister with a

disorder. He and his colleagues in 1994 have published a review of the
major literature worldwide on twin studies of schizophrenia. The overall
pairwise concordance rate is 28% in monozygotic twins and 6% in
dizygotic twins. This suggest that a reduction in shared genes from 100%
to 50% reduces the risk of schizophrenia by nearly 80% also note that
sharing 50% of one's genes with a core-twin with schizophrenia is
associated with a lifetime risk for schizophrenia of 6% although this is
low in absolute terms it is markedly higher than the baseline risk of less
than 1% found in the general population. Other studies (Squire et al,
2003) indicate 45-50% concordance rate for identical twins compared to
only 15% concordance rate for fraternal twins. This shows the
monozygotic twins are much more likely to develop schizophrenia than
dizygotic twins.

 If schizophrenia were exclusively a genetic disorder the concordance rate

for identical twins would of course be 100%. Although monozygotic
concordance rates vary from one twin study to another and although some
researchers report higher rates than the 28% reported by Torrey et al, they
are never close to 100% .

 Two conclusions can therefore be made

 Genes undoubtedly play a role in causing schizophrenia
 Genes themselves are not the whole story

 Twin studies provide some of the most solid evidence that the
environment plays an important role in the development of schizophrenia
but why one monozygotic twin should develop schizophrenia when his or
her core twin does not, is a fascinating question.

 Torrey 1994, also found the following differences between schizophrenic

and non-schizophrenic core twins :
 30% of the discordant affected twins were described as being different
suggesting CNS dis-function.
 Discordant affected twins showed widespread brain changes.
 Discordant affected twins showed widespread brain changes though they
were not related to clinical aspects of schizophrenia indicating that
behavioural manifestation of schizophrenia was related to some other
factors.

 A great deal of research attention is now being directed at studying people

with a non genetic liability for schizophrenia. Historically, the most
important participants to study in this regard have been monozygotic
twins who are discordant for schizophrenia. This investigative strategy
was pioneered by Fischer 1971 & 1973 in an ingenious study. Fischer
reasoned that genetic influences if present would be just as likely to show
up in the offspring of the twins without schizophrenia in discordant pairs
as they would be to show up in the offspring of the twins with
schizophrenia. And in a search of official records in Denmark Fischer
found exactly that. In a follow up of Fischer's participants Gottesmen and
Bertenson 1989, report an Age corrected incident rate for schizophrenia
of 17.4% for the offspring of the monozygotic twins without
schizophrenia. This rate which far exceeds normal expectancy was not
significantly different from that for offspring of the twins with
schizophrenia in discordant pairs or from that for offspring of dizygotic
schizophrenia. assuming that an exposure to an Aunt or Uncle with
schizophrenia would have at most limited etiology significance. These
results lend in impressive support to the genetic hypothesis. They also
indicate that a predisposition to schizophrenia may remain "unexpressed"
( as in the twins without schizophrenia in discordant pairs) unless
"released" by unknown environmental factors.

 ADOPTION STUDIES

 The assumption that monozygotic twins and dizygotic twins have equally
similar environments can create some problems when we try to interpret
the findings of twin studies.

 Interpretative problems with twin studies

 Challenging equal environment assumption - twin studies are based on
the assumption that monozygotic twins and dizygotic twins differ only in
terms of their genes. Equal environment assumption states that the
environmental conditions of monozygotic twins and dizygotic twins are
the same . This may not be true as there is evidence to indicate that
monozygotic twins are treated more alike by their family ( have more
similar environment) and others are compared to dizygotic twins.
 Problem of "monochorionic" twins - also at least 2/3rd of the
monozygotic twins are "monochorionic" meaning that they share the
blood supply ( as they share one placenta) . One study found that the
concordance rate of such monozygotic twins was almost double the
concordance rate for the dizygotic twins who had separate placentas
( Davis & Phelps, 1995) . So the higher concordance rate may not be due
to "tainted" but due to intrauterine factors involved in schizophrenia.
 Other factors - some researchers also suggest that identical twins are
identical only till the splitting of the zygote after that a host of influences
may be affecting the twins differently such as chromosomal changes,
gene mutations, differences in circulation and oxygenation, different
response to exposure agents etc.

 Several studies have attempted to overcome the shortcomings of the twin

method in achieving a true separation of hereditary from environmental
influences by using what is called the adoption strategy. Here
concordance rates for schizophrenia are compared for the biological and
the adopted relatives of persons who have been adopted out of their
biological families at an early age ( preferably at birth) and have
subsequently developed schizophrenia. If concordance is greater among
the patients biological than adoptive relatives a hereditary influence is
strongly suggested the reverse pattern would argue for environmental
causation.
 The first study of this kind was conducted by Heston in 1966. Heston
followed up 47 children who had been born to mothers who were in a
state mental hospital suffering from schizophrenia. The child had been
placed with relatives or into foster homes within 72 hours of their birth. In
his follow up study heston found that 16.6% of these children were later
diagnosed with schizophrenia. In contrast none of the 50 control children
 developed schizophrenia. In addition to the greater probability of being
diagnosed with schizophrenia the offspring whose mothers had
schizophrenia were also more likely to be diagnosed as mentally retarded,
neurotic or Psychopathic ( meaning anti-social). They also had been
involved more frequently in criminal activities and had spent more time
in penal (jail) institutions. These findings are often taken to suggest that
any genetic liability conveyed by the mother is not specific to
schizophrenia but also includes a liability for other forms of
psychopathology but we must be careful about drawing such a
conclusion. Hesten's study provided no information about
psychopathology in the fathers of the children. We therefore, cannot
know to what extent some of the problems the children had were due to
genetic liability conveyed by their fathers.

 Hesten's study began by identifying mothers with schizophrenia and then

traced what had happened to their adopted offspring. An alternative
approach involved locating adult patients with schizophrenia who were
adopted early in life and then looking at rates of schizophrenia in their
biological and adopted relatives. A large-scale and multi-faceted adoption
study of this time was undertaken in Denmark with Danish and American
investigators working in collaboration. As would be expected on the basis
of a genetic model the data showed a preponderance of schizophrenia and
"schizophrenia spectrum problems' ' ( for example, schizotypal and
paranoid personality disorder) in the biological relatives of adoptees with
schizophrenia. More specifically 13.3% of the 105 biological relatives
had schizophrenia or schizophrenia spectrum disorders themselves. In
contrast only 1.3% of the 224 adoptive parents showed such problems.

 Quality of the adopted family - Tienari et al, 2004 have provided further
evidence of a genotype- environment interaction in schizophrenia. Using
interviews the researchers first looked at the quality of the family
environment in which the adopted children were raised, then looked at
what happened to the children who were raised in healthy vs
dysfunctional families. The degree of adversity in the family environment
predicted later problems in the adopted children. However, only those
children who were raised in dysfunctional families and had high genetic
risk went on to develop schizophrenia related disorders. Children at high
 genetic risk who were raised in a healthy family environment did not
develop problems any more frequently than did children at low genetic
risk. These findings are important because they suggest that our genetic
makeup may control how sensitive we are to certain aspects of our
environments. If we have no genetic risks certain kinds of environmental
influences may not affect us very much but if we have high genetic risk
we may be much more vulnerable to certain types of environmental risks
such as high communication deviance or adverse family environment.
Findings such as these also raise the exciting possibility that certain kinds
of environment may protect people with a genetic susceptibility to
schizophrenia from ever developing the illness. Thus the Finnish adoptive
studies have provided strong confirmation of the Diathesis-Stress Model
as it applies to the origins of schizophrenia.

 Conclusion
 Family studies tell us that schizophrenia runs in families and twin and
adoption studies help us explore the relative contributions of genes and
environment. These approaches also tell us about the genetic
heterogeneity of schizophrenia. For example, in addition to higher rates of
schizophrenia, higher rates of schizotypal personality disorder are also
found in the relatives of patients with schizophrenia ( Kendler et al,
1993). This supports this idea of the schizophrenia spectrum and suggests
that a genetic liability to schizophrenia can sometimes manifest itself in a
form of pathology which is "schizophrenia-like" but not exactly
schizophrenia itself.