Schizophrenia

Group 2A (2014)

Brain of a Schizophrenic patient:

PET scan shows disruption in brain activity,
changes in brain structures (eg. Ventricles) &
decrease function in the frontal cortex.
 Schizophrenia
• Define as major mental disorder characterized
by disturbance of :
i. Thinking
ii. Emotion
iii. Behaviour

• Often accompanied by deterioration in

personality and functioning
Epidemiology
• Worldwide (WHO)
 affecting about 7/1000 of the adult population
 affects about 24 million people wordwide
 mostly in the age group 15-35 years.
 the incidence is low (3-10,000) but the
prevalence is high due to chronicity.
• Malaysia
 National Mental Health Registry report that
7351 cases had been registered from 2003 to
2005.
 the median incidence rate was 15.2 per
100,000 (range of 7.7 to 43.0 per 100,000
 The incidence was noted higher in males,
urban and migrant population.
 Findings of Malaysia
National Mental Health Registry
Report
a. Gender and age
• More than 60% schizophrenia cases in
Malaysia were males.
• peak age of patient’s presentation was at the
age of 30 in which males developed earlier
illness compared to female.
b. Ethnic group
c. Marital status and occupation
d. Body weight
e. Duration of Untreated Psychosis (DUP)
f. Family history
• A total of 21.6% had family history of mental
illness, 20% had some
form of co-morbidity,
g. co-morbid conditions (substance abuse)
h. Medical co-occuring conditions
• Diabetes mellitus and hypertension being the
most common ones
Predisposing Factors
• Genetic
Those with family history of schizophrenia
• Parents 6%
• Siblings 9%
• Children 13%
• Dizygotic twin 17%
• Children with two affected parents 46%
• Monozygotic twin 48%
• Social
• Cannabis abusers
• Individual living in higher level of urbanisation
(1.40-fold increased risk)

• Environment
• Those with history of childhood central
nervous system infection.
• history of obstetric complications •
Dopamine Hypothesis
 DOPAMINE HYPOTHESIS

The Dopamine hypothesis states that the brain of

schizophrenic patients produces more
dopamine than normal brains.
– Evidence comes from
– studies with drugs
– post mortems
– pet scans
 Elevated Level of Dopamine In The
Normal Level of Dopamine
Brain of a Schizophrenic Patient
In The Human Brain
(specifically the D2 receptor)

 Neurons that use the transmitter ‘dopamine’ fire too often and transmit too
many messages or too often.
 Certain D2 receptors are known to play a key role in guiding attention.
 Lowering DA activity helps remove the symptoms of schizophrenia
 ROLE OF DRUGS

– Amphetamines (agonists) lead to increase in DA levels

– Large quantities lead to delusions and hallucinations
– If drugs are given to schizophrenic patients their
symptoms get worse
 Parkinson’s disease
• Parkinson’s sufferers have low levels
of dopamine
• L-dopa raises DA activity
• People with Parkinson's develop
schizophrenic symptoms if they take
too much L-dopa

– Chlorphromazine (given to schizophrenics) reduces

the symptoms by blocking D2 receptors
 POST MORTEM

Falkai et al 1988
 Autopsies have found that people with
schizophrenia have a larger than usual number
of dopamine receptors.
 Increase of DA in brain structures and receptor
density (left amygdala and caudate nucleus
putamen)
• Concluded that DA production is abnormal for
schizophrenia
SIGNS AND SYMPTOMS
In general, the symptoms of schizophrenia can be divided into
three catogories:
 Positive
 Negative
 cognitive symptoms.

However, patients may develop their own unique combination

of symptoms.
POSITIVE SYMPTOMS

 Delusions
 Hallucinations
 Disorganised speech/thinking (thought disorder or loosening of
associations)
 Grossly disorganised behaviour
 Catatonic behaviours
 Other symptoms:
• Affect inappropriate to the situation or stimuli
• Unusual motor behaviour (e.g. pacing and rocking)
• Depersonalisation
• Derealisation
• Somatic preoccupations

These tend to respond more robustly to the current antipsychotic

medications
NEGATIVE SYMPTOMS
The symptoms that appear to reflect a diminution or loss of normal
emotional and psychological function which includes:
i. Flat affect
• the reduction in the range and intensity of emotional expression:
facial expression, voice tone, eye contact, and body language
ii. Alogia or poverty of speech
• the lessening of speech fluency and productivity, thought to reflect
slowing or blocked thoughts, and often manifested as short, empty
replies to questions
iii. Avolition
• psychological state characterized by general lack of drive, or
motivation to pursue meaningful goals.
• e.g. no longer interested in going out and meeting with friends, no
longer interested in activities that the person used to show enthusiasm
for, no longer interested in much of anything, sitting in the house for
many hours a day doing nothing
iv. Anhedonia
• inability to experience pleasure from activities usually found enjoyable
v. Attention (poor)

Negative symptoms are less obvious and often persist even after the
resolution of positive symptoms.
COGNITIVE SYMPTOMS

Cognitive symptoms refer to the difficulties with concentration and

memory
i.e.:
• Disorganised thinking
• Slow thinking
• Difficulty understanding
• Poor concentration
• Poor memory
• Difficulty expressing thoughts
• Difficulty integrating thoughts, feelings and behaviour

These symptoms may poor work and school performance

Three Phase:

Symptoms of schizophrenia usually present in three phases:

1. Prodromal
• Decline in functioning that precedes the first psychotic episode
• The patient may become socially withdrawn and irritable
• He or she may have physical complaints and/or newfound interest in religion
or the occult

2. Psychotic
• Perceptual disturbances, delusions, and disordered thought process/content

3. Residual
• occurs between episodes of psychosis
• It is marked by flat affect, social withdrawal, and odd thinking or behaviour
(negative symptoms)
• Patient can continue to have hallucinations even with treatment
Scheinder’s symptoms of first rank’

 Auditory hallucinations taking the form of the following:

 Voices repeating the subject’s thoughts out loud or anticipating their thoughts
 Two or more hallucinatory voices discussing the subject or arguing about then in
the third person
 Voices commenting on the subject’s thoughts or behaviour, often in the form of a
running commentary

 The sensation of alien thoughts being put into the subject’s mind by some external
agency (thought insertion) or of their own thoughts being taken away (thought
withdrawal)

 The sensation that the subjects thinking is no longer confined to their own mind,
but is instead shared by, or accessible to, others (thought broadcasting)
 The sensation of feelings, impulses, or acts being experienced or carried out under
external control, so that the subject feels as if they were being hypnotised or had
become a robot (delusion of control)

 The experience of being a passive and reluctant recipient of bodily sensations

imposed by some external agency (somatic delusion)

 Delusional perception – a delusion arising fully fledged on the basis of a genuine

perception which others would regard as commonplace an unrelated
Diagnosis of Schizophrenia

DSM-V Criteria
 Two or more of the following must be present for at least 1 month:
1. Delusions
2. Hallucinations
3. Disorganized speech (e.g Frequent derailment or incoherence)
4. Grossly disorganized or catatonic behaviour
5. Negative symptoms (e.g Diminished emotional expression or avolition)
- One of the two symptoms must be delusions, hallucinations,
or disorganized speech.

 Level of functioning is markedly below the level achieved prior to the

onset.
 Duration of illness for at least 6 months which is well distinguished from
schizophreniform disorder.
 Symptoms not due to medical, neurological or substance-induced disorder
  Makes the distinction between schizophre­nia and an “autism spectrum
disorder or a communication disorder”. 
Schizophrenia Subtypes
 Paranoid type
Highest functioning type, older age of onset. Must
meet the following criteria:
• Preoccupation with one or more delusions
(persecutory/grandeur) or frequent auditory
hallucinations (single theme, persecutory)
• No predominance of disorganized speech,
disorganized or catatonic behavior, or inappropriate
affect
They are typically guarded, tense, reserve and
sometimes hostile. Intelligence remain intact
 Disorganized type (Hebephrenia)
Poor functioning type, early onset. Must meet
the following criteria:
• Disorganized speech (loosening of
association )
• Disorganized behavior
• Flat or inappropriate affect
 Catatonic Type
Rare. Must meet at least two of the following
criteria:
• Motor immobility
• Excessive purposeless motor activity
• Extreme negativism or mutism
• Peculiar voluntary movements or posturing
(may hold awkward position for a long time)
 Undifferentiated Type
Characteristic of more than one subtype or
none of the subtypes
• Prominent delusion
• Hallucination
• Incoherence
• Grossly disturbed behavior
 Residual Type
• Prominent negative symptoms (such as
flattened affect or social withdrawal)
• Minimal evidence of positive symptoms (such
as hallucinations or delusions)
 Brief Psychotic, Schizophreniform,
Schizoaffective Disorder
Schizophreniform disorder - symptoms have lasted
between 1 and 6 months, whereas in schizophrenia
the symptoms must be present for more than 6
months.

Brief Psychotic Disorder - Patient with psychotic

symptoms as defined for schizophrenia; however, the
symptoms last from 1 day to 1 month. Symptoms must
not be due to general medical condition or drugs. This
is a rare diagnosis, much less common than
schizophrenia.
Schizoaffective disorder - Meet criteria for either major
depressive episode, manic episode, or mixed episode
(during which criteria for schizophrenia are also met)
•  Have had delusions or hallucinations for 2 weeks in the
absence of mood disorder symptoms (this condition is
necessary to differentiate schizoaffective disorder from
mood disorder with psychotic features)
• Have mood symptoms present for substantial portion of
psychotic illness
Schizophreniform disorder
• Episode lasts for 1-6m or <6m
Schizoaffective disorder
• (Major Depressive episode/Manic episode/Mixed
Episode)+ Psychotic symptoms (Criteria A)
Brief Psychotic Disorder
• Disturbance <1m but >1d
Management
 • Management of schizophrenia may be
divided into following phase :
1) Prodromal phase
-Impairments in psychosocial functioning, odd and eccentric behaviour, poor communication and motivation, blunted or flattened affect
and neglect of personal hygiene.
-No treatment

2) Acute phase
-Positive symptoms appear
-With adequate treatment, the symptoms will disappear in most patients.
-However, negative symptoms may persists

3) Relapse prevention

4) Stable phase
- After 10 years, patient become more stable with sign of improvement

5) Poor response to treatment

• Criteria for hospitalization:
o Risk of harm/ neglect to self or others
o Deterioration in psychosocial functioning
o Serious/ life- threatening drug reactions
 Pharmacological treatment

• Anti- psychotics are the mainstay of

pharmacological treatment in schizophrenia
• These medications treat the symptoms of disorder
and do not cure shcizophrenia
• The anti- psychotic drugs include two major classes:
i) dopamine receptor antagonists.
ii) Serotonin- dopamine antagonists (SDA)
• All APs are different in their efficacy and side effects
Dopamine receptor antagonists
• Effective in treatment of positive symptoms of
schizophrenia
• Cause extrapyramidal side effects such as parkinsonism
and hyperprolactinaemia.
• Eg: haloperidol (haldol), chlorpromazine (thorazine),
perphenazine, sulpride, trifluoperazine, fluphenazine,
zuclopenthixol, flupenthixol
 Serotonindopamine antagonists (SDA)
• Known as atypical antipsychotic drugs
• Effective against negative symptoms
• Fewer neurological and endocrinological side effects. But causing
metabolic syndrome (weight gain, dyslipidemia, and glucose
intolerance)
• Eg: clozapine, risperidone (risperdal), olanzapine, quetiapine,
ziprasidone, aripriprazole, paliperidone, amisulpride
 Other biological therapies

• Electroconvulsive therapy
o To achieve rapid and short- term improvement of
severe symptoms after an adequate trial of other
treatment options has proven ineffective and/ or when
the condition is considered to be life- threatening. Eg:
i) catatonic schizophrenia
ii) shcizophrenia with prominet affective symptoms
iii) schizophrenia with previous improvement with
ECT
 Psychosocial therapies

• Objectives:

o Enable persons who are severely ill to develop social and vocational
skills for independent living
o To improve individual’s ability to handle stressful life events
o Increase adherence to medications
o Promote better communication and coping skills
o Enhance quality of life
o Promote recovery
• Types of psychosocial therapies:-

o Family- oriented therapies

o Pychoeducation
o Social skills training
o Counseling and supportive psychotherapy
o Group therapy
Prognosis
• Several studies have shown that:-
o over 5 to 10 years period after first psychiatric
hospitalization for schizophrenia, approximately
only 10 to 20 % patients have a good outcome.

o >50% patients having poor outcomes, repeated

hospitalization, exacerbations of symptoms,
episodes of major mood disorders and suicide
attempts.
Predictors for poor outcome

Features of the illness Insidious onset

Long 1st episode
Previous psychiatric history
Negative symptoms
Younger age at onset
Features of the patient Male
Single, separated, widowed or divorced

Poor psychosexual adjustment

Poor employment
Social isolation
Poor compliance