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Prof. Dr. Fareed A.

Minhas
Head, Institute of Psychiatry
Rawalpindi General Hospital
Rawalpindi
"Schizophrenia is a cruel disease. The lives of those
affected are often chronicles of constricted
experiences, muted emotions, missed opportunities,
unfulfilled expectations. It leads to a twilight
existence, a twentieth-century underground man... It is
in fact the single biggest blemish on the face of
contemporary medicine and social services; when the
social history of our era is written, the plight of
persons with schizophrenia will be recorded as having
been a national scandal."

- E. Fuller Torrey, M.D., Surviving Schizophrenia


Characterized in general by fundamental
and characteristic disorders in thinking
and perception, and by inappropriate or
blunted affect

Clear consciousness is usually


maintained

Intellectual capacity retained though


cognitive impairment may set in over time

Disorder of thinking, emotion, volition


and perception along with disintegration
Annual incidence
between 0.1 and 0.5 per
1000

Onset characteristically
between ages 15 & 45

Equal among men and


women but mean age of
onset is 5 years earlier in
men

Lifetime risk between


In America
7.0 and 9.0 per 1000 alone, 2.2
million people
Prevalence equal in
are affected
WHERE DO PEOPLE SUFFERING FROM IT LIVE??
Stigmatization
Knowledge of the illness lags behind facts
->discrimination

Fear of violence
Fear of criminal intentions
Fear of unknown and aversion to illness

Impact on the persons life


Work limitations such as difficulty performing multiple
tasks, interacting with co-workers, accepting criticism or
supervision, customer service/contact. Perform
inconsistently and may need work space with low
stimulation(stress)
Interpersonal relationships are difficult, mostly live alone
or with family
Impact on families
Sorrow We feel like we have lost our child
Anxiety We are afraid to leave him alone or hurt his
feelings
Fear Will he harm himself or others?
Shame and guilt Are we to blame? What will people
think?
Feelings of isolation No one can understand
Bitterness Why did this happen to us?
Ambivalence towards the affected person
Anger and jealousy of siblings
Depression / Sleeplessness / Weight loss / Social
withdrawal
Total denial of the illness or its severity
Blaming each other
Community costs
Schizophrenia costs Canadians more than $2.3 billion in
direct health care costs and an additional $2 billion in
support costs such as welfare, family benefits and
community support services, for a total of $4.3 billion
annually. The cost in terms of human suffering is
immeasurable...
People with this disease use nicotine and street drugs
excessively
Suicide rates are high (10 percent mostly young males)
Studies show increased prevalence
of various diseases in schizophrenics
such as female breast cancer, MI (s)
Infections, type II diabetes mellitus
Homelessness
Accidents
PARANOID SCHIZOPHRENIA
Commonest type
Predominant well-organized paranoid delusions
Thought processes and mood relatively spared
Disturbance of affect, volition, speech and catatonia mild /
absent
SIMPLE SCHIZOPHRENIA
Insidious development of odd behavior, social withdrawal
and declining performance at work
Clear schizophrenic symptoms might be absent

CATATONIC SCHIZOPHRENIA
Prominent psychomotor disturbances with alteration
between hyperkinesis and stupor, or automatic obedience
and negativism
Posturing / episodes of violent excitement
HEBEPHRENIC SCHIZOPHRENIA

Affective changes are prominent; delusions and


hallucinations fleeting and fragmentary; behavior
irresponsible and unpredictable
Mannerisms are common
Mood is shallow/inappropriate followed by giggling or self-
satisfied/self-absorbed smiling
Hypochondriacal complaints common
Thought is disorganized and speech rambling/incoherent
OTHER CATEGORIES
Undifferentiated
Residual
Post-schizophrenia depression
Schizophreniform disorder not otherwise specified
POSITIVE SYMPTOMS (Delusions, Hallucinations)
NEGATIVE SYMPTOMS (apathy, lack of drive, social
withdrawal)
THE ACUTE SYNDROME
SYMPTOM FREQUENCY
Lack of insight into illness (%)
Auditory hallucinations 97
Ideas of reference 74
Suspiciousness 70
Flatness of affect 66
Voices speaking to the patient 66
Delusional Mood 65
Delusions of persecution 64
Thought alienation 64
Thoughts spoken aloud 52
THE CHRONIC SYNDROME

CHARACTERISTIC FREQUENCY
Social withdrawal %
Under activity 74
Lack of conversation 56
Slowness 54
Over activity 48
Odd ideas / behavior 41
Depression 34
Neglect of appearance 34
Odd postures and movements 30
Threats or violence 25
Socially embarrassing 23
behavior 8
VARIATION OF THE CLINICAL PICTURE
Different features may predominate within a
syndrome eg. In the acute syndrome one may have
a predominant paranoid delusion and another may
have a thought disorder
Some may have features of both syndromes
Depressive symptoms / Water intoxication

FACTORS MODIFYING CLINICAL FEATURES

Amount of social stimulation of the patient


under stimulated ones have mostly negative
symptoms and over stimulated ones positive
symptoms
Social background previously religious delusions
were common
Intelligence people of low intelligence exhibit
Minimum of one very clear symptom(two or more if
less clear) belonging to any one of the groups (a)-
(d) or from at least two of the groups (e)-(h) during
a period of one month or more
(a) Thought echo/ insertion or withdrawal and
broadcasting
(b) Delusions of control,influence,passivity; delusional
perception
(c) Hallucinatory voices as a running commentary,
third-person or somatic hallucinations
(d) Persistent delusions that are inappropriate and
impossible
(e) Persistent hallucinations or over-valued ideas
(f) Breaks/interpolations in train of thought,
neologisms
A. CHARACTERISTIC SYMPTOMS OF ACTIVE PHASE
(delusions/hallucinations/disorganized
speech/catatonia/alogia)
B. SOCIAL/OCCUPATIONAL DYSFUNCTION in at least
one major area of functioning such as work,
interpersonal relations or self-care
C. DURATION persistent for at least 6 monthswith
at least one month of symptoms of criterion A
D. SCHIZOAFFECTIVE AND MOOD DISORDER
EXCLUSION
E. SUBSTANCE/GENERAL MEDICAL CONDITION
EXCLUSION
F. RELATIONSHIP TO A PERVASIVE DEVELOPMENTAL
DISORDER
ORGANIC SYNDROMES (drug-induced states,
temporal lobe epilepsy, acute brain syndrome of the
elderly, dementia)

MOOD DISORDER

PERSONALITY DISORDER

CHILDHOOD AUTISM ASPERGERS


SYNDROME
Study commenced in 1990 investigating about
20% genomes in large families of history of
schizophrenia in east Quebec show association
areas on chromosomes
11q / 3q / 18q / 6p
STRONG EVIDENCE FOR SCHIZOPHRENIA
SUSCEPTIBILITY GENE 6P22-P24 AND 11Q21-22

Anticipation (increasing severity or early age of


onset of disease in successive generations) is
found in Schizophrenia
A recent study by molecular biologists at UC Irvine
isolated a gene, hSKCa3 located on 22q, which leads to an
increased risk to schizophrenia. This isolated gene
American Journal of Genetics(Miziade M et
contains a characteristic CAG repeat
There is a strong genetic component however
only 48% concordance among identical twins
says that is not all
THE DOPAMINE HYPOTHESIS
SHOWS A
SIGNIFICANT
INCREASED
NUMBER OF
DOPAMINE
RECEPTORS IN A
SCHIZOPHRENIC
BRAIN

ROLE OF AMINO ACIDS IN SCHIZOPHRENIA

Glutamate neurotransmitters might have a role


evidence of increased presynaptic/postsynaptic
uptake sites for glutamate in orbito-frontal cortex
and decreased density of glutamate receptors in the
left hippocampus (SEE NEXT SLIDE)
NORMAL
STRUCTURE
People with schizophrenia have smaller and lighter brains
Evidence of enlarged cerebral ventricles
Cytoarchitectural disturbances have been noted
There is evidence of regional cortical loss volume
changes in gray matter

3D profile of gray matter


loss in brains of
teenagers with early-
onset disease.TEMPORAL
and FRONTAL areas most
affected (red shows
maximum effect). These
areas are responsible for
memory, hearing, motor
functions and attention
Frontal composite
variability of normal and
schizophrenic brains by
gender
Shows
Significant structural
variability suggestive of
changes

Normal vs. Schizophrenia


Composite variability
among 15 male subjects
VOLUME OF INTEREST
superimposed over three
orthogonal slices of the
schizophrenic brain it
is simply a sphere of 60
mm radius between
midline decussations of
ant. And post.
commissures

Variability in the sulcal


anatomy of the brain
between normal and
schizophrenic brains is
also noted
3D average surface
representation and
variability maps of the
lateral ventricles -
highest variability in the
posterior horns noted

: MRI imaging showing


differences in brain
ventricle size in twins -
one schizophrenic, one
not. (image courtesy NIH -
Dr. Daniel Weinberger,
Clinical Brain Disorders
Branch)
Coronal MR scans from a normal
comparison subject (left), and chronic
schizophrenic (right). Note increase in
CSF in right amygdala-hippocampal
complex. (image courtesy of
Harvard University Schizophrenia Projec
t
N

SCZ

HYPOFRONTALITY : At rest During card sorting

DISARRAY of the
hippocampal
cytoarchitecture
and cingulate
gyrus
Soft signs have been reported in many studies
commonly stereognosis, graphaesthesia, balance
and proprioception probably due to defects in
integration of proprioceptive and other sensory
information (Rochford et al-1970/Sanders et al-1992)
Movement disorders common such as dyskinesias
and extrapyramidal or parkinsonian signs. Initially
the argument was that these are side-effects of
anti-psychotic drugs but now a prevalence of 12%
of spontaneous dyskinesias has been found in 9
different recent studies of people who never
received anti- psychotics. Also 23% prevalence of
parkinsonian signs is found in the same category.
Decreased pain perception exact mechanism not
know..no studies
EEGs of schizophrenics show increased theta
activity, fast activity and paroxysmal activity with
scalp electrodes. More abnormal EEGs were seen in
patients never treated. Using deep implanted
electrodes spike abnormalities in septal region
and secondarily in the hippocampus and amygdala.
Also there was abnormality in deep frontal and
subthalmic regions
Evoked potential response (p300) makes use of
the persons ability to identify a target stimulus
among irrelevant stimuli and this is lower in
schizophrenics and their first-degree relatives
Eye-tracking studies defective performance by
schizophrenics (Freidman et al-1992 and Muir et al-
Cognitive deficits proven by various studies.
Studies using subjects who never received anti-
psychotics also show significant results.
Main areas of deficit are verbal learning and
memory. Less commonly, attention and vigilance as
well as visuo-motor processing.
Latest study by Schuepbach et all in 2002 in
which 20 patients compared to 21 controls showed
significant deficits on the Stroop test for selective
attention
Use of comparatively new and technically complex
methods POSITRON EMISSION TOMOGRAPHY (PET) ;
SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY
(SPECT) and FUNCTIONAL MAGNETIC RESONANCE
IMAGING (fMRI)
10 studies conducted to date of patients without
anti- psychotic treatments. 8 show significant deficits
in the dorsolateral prefrontal cortex at the onset on
disease
Decreased blood flow in prefrontal and frontal
areas
PERINATAL FACTORS : Birth complications, season,
influenza

CHILDHOOD DEVELOPMENT/ ANTECEDENTS :


Greater hostility towards strangers, reading and speech
difficulties

PERSONALITY FACTORS : Asthenic built, schizoid


traits

SEX AND AGE OF ONSET : Myelination of frontal and


temporal cortex around puberty, sex hormone changes
PSYCHODYNAMIC THEORIES
FAMILY
Deviant role relationships
Disordered family communications

CULTURE
OCCUPATION AND SOCIAL CLASS
PLACE OF RESIDENCE
MIGRATION / SOCIAL ISOLATION
PSYCHOSOCIAL STRESSES
According to the BIO-PSYCHO-SOCIAL MODEL

BIOLOGICAL TREATMENT
ANTI-PSYCHOTIC DRUGS
Conventional or Standard Antipsychotics are
phenothiazines, butyrophenones, diphenylbutyl pipiredines,
thioxanthenes and substituted benzamides. These include:
chlorpromazine (Thorazine); fluphenazine (Prolixin);
haloperidol (Haldol); thiothixene (Navane); trifluoperazine
(Stelazine); perphenazine (Trilafon) and thioridazine
(Mellaril).
Atypical Antipsychotics are newer drugs with fewer side
effects and include risperidone (Risperdal); clozapine
(Clozaril) and olanzapine (Zyprexa).
Side-effects Commonly dry mouth, constipation, blurred
vision and drowsiness. Less commonly decreased libido,
menstrual changes
Extrapyramidal effects : Parkinsonian tremors,
Anti-psychotic preparations available
Oral drugs Tablets and suspensions
Injectables Short acting( Haloperidol, zuclopenthixol
acetate) or depot preparations(zuclopenthixol decanoate,
fluphenazine)
ECTs
Traditional indications are catatonic stupor and severe
depressive symptoms in schizophrenia.
ANTI-DEPRESSANTS AND MOOD STABILIZERS
Depression is a part of the syndrome of schizophrenia.
Value of use of anti-depressants is not proven, may be
helpful in chronic syndrome but might worsen active
psychosis.
Value of lithium in treatment is uncertain. If a
schizoaffective case, some benefit might be present.
PSYCHOLOGICAL TREATMENT

INDIVIDUAL PSYCHOTHERAPY
FAMILY EDUCATION
SELF-HELP GROUPS
Good motivation and productivity from patient is
essential
WORKING WITH RELATIVES working with emotional
expressions within family is most beneficial
BEHAVIORAL TREATMENT include token economies
and cognitive behavior therapy (specially for positive
symptoms as they are amenable to structured reasoning)

SOCIAL TREATMENT

REHABILITATION include social and vocational training


and improvement of communication skills as the onset of
the illness is at a point where they are training for skilled
work.
CASE MANAGEMENT (followed in US)
Most consumers with severe or chronic schizophrenia will
have a case manager. The role of the case manager is to
assist in coordinating all the services that the consumer
may need. See figure below as an example of how a case
manager can work with other professionals and agencies.
Two different approaches to preventing schizophrenia that
are currently being researched:
1. Preventative measures that are taken well prior to
any measurable signs of the early phase of schizophrenia
(also called the prodromal phase, in medical terms)
2. Preventative measures taken during the prodromal
period of schizophrenia. (People typically show some early
signs of schizophrenia well before the full development of
schizophrenia).
REDUCING THE CHANCE OF GETTING SCHIZOPHRENIA
Street Drugs increase risk of Schizophrenia particularly
cannabis and marijuana
Enriched Educational, Nutrition and Social Environments
Lower Risk of Schizophrenia
Essential fatty acid (EFA) deficiency and resulting lipid
membrane abnormalities may increase risk of schizophrenia
Antioxidant Intake may reduce risks of schizophrenia and
Country life (vs. city living) before age 15 is associated with
lower rates of schizophrenia
REDUCING THE CHANCE OF GETTING IT AT BIRTH
Maternal infections during pregnancy are associated with
increased risk of schizophrenia mostly flu
Pregnancy and baby delivery complications are associated
with increased risk of schizophrenia
Season of Birth - Low Sunlight Exposure/Vitamin D is
associated with higher risk of schizophrenia
Older Age of Father increases risk of Schizophrenia due to
high levels of DNA damage in sperms of father
Lead and other Toxic Exposures to Pregnant Women Triples
Risk of Schizophrenia for Child
X-Ray Radiation during Pregnancy may increase risk of
schizophrenia for child
Natural course of
Schizophrenia as
typically
described

ICD 10 CLASSIFICATION / DSM IV


CLASSIFICATION
-Continuous - Episodic with interepisodic
- Episodic+Progressive deficit residual symptoms
- Episodic+Stable deficit - Episodic with no
interepisodic
- Episodic remittent residual symptoms
- Incomplete remission -
Continuous(+negative prominence)
Good prognostic factors :
Sudden onset Married
Short episode Good psychosexual
adjustment
No previous history
Good previous
Prominent affective symptoms
personality
Paranoid type of illness Good work record
Older age of onset Good social relationships
Poor prognostic signs : Good compliance
Insidious onset
Single/separated/widow/divo
Long episode rced
Previous psychiatric history Poor psychosexual
Negative symptoms adjustments

Abnormal previous
Enlarged lateral ventricles/Male
personality
Younger age at onset
Poor work record
Social isolation
EARLY DETECTION AND INTERVENTION may
contribute to lower incidence and prevalence of florid
schizophrenia. These programs combine (1) early
detection of psychotic features by family practitioners
and other primary care providers and (2) close liaison
with mental health professionals well trained in
psychiatric assessment and treatment strategies
effective in reducing the prevalence of established
cases of schizophrenia. Long-term monitoring for
signs of recurrence of these sub-threshold psychotic
episodes, with further intervention as needed,
appears essential to maintain these benefits.
Schizophrenia Bulletin, 22(2): 271-282, 1996
Linszen D, Lenoir M, de Haan L, Dingemans P, Gersons B (1998).
British Journal of Psychiatry 172 (Suppl 33): 84-89.

NEWER ANTI-PSYCHOTICS are comparatively safer


In 2001, Thompson's group produced the first time-
lapse images revealing a wave of tissue loss rolling
across the brains of schizophrenic children at the
Loss of upto 5 percent gray matter per year has
been recorded compared to 1 percent per year in
normal teenagers.
In 2002, Desmond Smith of the University of
California, Los Angeles and his colleagues developed
the technique called "voxelation" to study
Parkinson's disease in a mouse model. The problem
is that the trouble-making cells behind,
schizophrenia, for example, could be a small group
of upstarts in the brain's huge collection of
specialised cells. And to make the matter worse,
only a few of our 30,000 or genes may be misfiring in
these cells. Smith is now dissecting brain slices for
mapping. In five years, he expects to have a
complete genetic map of the healthy human brain
composed of 8000 voxels and a 300 voxel map of the
healthy mouse brain. At the same time, they will
begin developing genetic maps of abnormal brains.
ADHERENCE TO TREATMENT is a special
challenge for both the doctor and the patient as
paranoia and lack of insight of the patient often
interferes.
SIDE EFFECTS OF THE DRUGS make a person
refuse treatment.
Long-acting depot preparations are available
only for the older anti-psychotics. Future targets
include development of intramuscular newer anti-
psychotics.
Development of new drugs that act primarily
on receptors other than the dopamine system
Development of community programmes that
aid early detection of psychosis and protection of
the rights of the mentally ill
The schizophrenic experience can be a terrifying
journey through a world of madness no one can
understand, particularly the person travelling
through it. It is a journey through a world that is
deranged, empty, and devoid of anchors to reality.
You feel very much alone. You find it easier to
withdraw than cope with a reality that is
incongruent with your fantasy world. You feel
tormented by distorted perceptions. You cannot
distinguish what is real from what is unreal.
Schizophrenia affects all aspects of your life. Your
thoughts race and you feel fragmented and so very
alone with your craziness... (Janice Jordan an
author)

The worst thing about having schizophrenia is


the isolation and the loneliness...