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 patients 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

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

Normal Level of
Dopamine In The
Human Brain

Elevated Level of
Dopamine In The Brain of
a Schizophrenic Patient
(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

Parkinsons disease
Parkinsons 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
performance

poor work and school

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

Scheinders symptoms of first rank

Auditory hallucinations taking the form of the following:
Voices repeating the subjects 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 subjects thoughts or behaviour, often
in the form of a running commentary
The sensation of alien thoughts being put into the subjects 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 symptomsmustbedelusions,hallucinations,
ordisorganized 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 substanceinduced 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 lifethreatening. 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 individuals 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