Schizophrenia and Other

Psychotic Disorders
A.Jayalangkara Tanra MD,Ph.D.
Department of Psychiatry,
Faculty of Medicine,
Hasanuddin University,
Makassar,INDONESIA.

What is Psychosis?

Generic term
Break with Reality
Symptom, not an illness
Caused by a variety of conditions
that affect the functioning of the
brain.
Includes hallucinations, delusions
and thought disorder

Mood disorders

Functional
disorders
Schizophrenia
spectrum
disorders

P
S
Y
C
H
O
S
I
S

Substance
induced

Delirium
Dementia
Amnestic d/o

organic
mental
disorders

Differential Diagnoses: (Cont)

Personality
disorders
Schizoid
Schizotypal
Paranoid
Borderline
Antisocial

Miscellaneous
PTSD
Dissociative disorders
Malingering
Culturally specific phenomena:
Religious experiences
Meditative states
Belief in UFOs, etc

Schizophrenia

Definition

The schizophrenic disorders are characterized in

general by fundamental and characteristic distortions
of thinking and perception, and affects that are
inappropriate or blunted. Clear consciousness and
intellectual capacity are usually maintained although
certain cognitive deficits may evolve in the course of
time.
The most important psychopathological phenomena
include

thought echo
thought insertion or withdrawal
thought broadcasting
delusional perception and delusions of control
influence or passivity
hallucinatory voices commenting or discussing the patient in
the third person
thought disorders and negative symptoms.

Schizophrenia

Schizophrenia occurs with regular

frequency nearly everywhere in the world
in 1 % of population and begins mainly in
young age (mostly around 16 to 25
years).
Schizophrenia is defined by

a group of characteristic positive and negative

symptoms
deterioration in social, occupational, or
interpersonal relationships
continuous signs of the disturbance for at least
6 months

History

Emil Kraepelin: This illness develops relatively

early in life, and its course is likely deteriorating
and chronic; deterioration reminded dementia
(Dementia praecox), but was not followed by any
organic changes of the brain, detectable at that
time.
Eugen Bleuler: He renamed Kraepelins dementia
praecox as schizophrenia (1911); he recognized
the cognitive impairment in this illness, which he
named as a splitting of mind.
Kurt Schneider: He emphasized the role of
psychotic symptoms, as hallucinations, delusions
and gave them the privilege of the first rank
symptoms even in the concept of the diagnosis of
schizophrenia.

4 A (Bleuler)

Bleuler maintained, that for the diagnosis of

schizophrenia are most important the following four
fundamental symptoms:

affective blunting
disturbance of association (fragmented thinking)
autism
ambivalence (fragmented emotional response)

These groups of symptoms, are called four A s

and Bleuler thought, that they are primary for this
diagnosis.
The other known symptoms, hallucinations,
delusions, which are appearing in schizophrenia very
often also, he used to call as a secondary
symptoms, because they could be seen in any
other psychotic disease, which are caused by quite
different factors from intoxication to infection or
other disease entities.

Course of Illness

Course of schizophrenia:
continuous without temporary improvement
episodic with progressive or stable deficit
episodic with complete or incomplete remission

Typical stages of schizophrenia:

prodromal phase
active phase
residual phase

Clinical Picture

Diagnostic manuals:

lCD-10 (International Classification of Disease, WHO)

DSM-IV (Diagnostic and Statistical Manual, APA)

Clinical picture of schizophrenia is according to lCD10, defined from the point of view of the presence
and expression of primary and/or secondary
symptoms (at present covered by the terms
negative and positive symptoms):

the negative symptoms are represented by cognitive

disorders, having its origin probably in the disorders of
associations of thoughts, combined with emotional blunting
and small or missing production of hallucinations and
delusions
the positive symptom are characterized by the presence of
hallucinations and delusions
the division is not quite strict and lesser or greater mixture
of symptoms from these two groups are possible

Positive and Negative Symptoms

Negative
Alogia
Affective flattening
Avolition-apathy
Anhedonia-asociality

Positive
Hallucinations
Delusions
Bizarre behaviour
Positive formal thought
disorder

Attentional impairment

Andreasen N.C., Roy M.-A., Flaum M.: Positive and negative symptoms. In: Schizophrenia,
Hirsch S.R. and Weinberger D.R., eds., Blackwell Science, pp. 28-45, 1995

The Criteria of Diagnosis

For the diagnosis of schizophrenia is necessary
presence of one very clear symptom - from point a) to d)
or the presence of the symptoms from at least two groups from point e) to h)
for one month or more:
a)

b)

c)

d)

the hearing of own thoughts, the feelings of thought

withdrawal, thought insertion, or thought broadcasting
the delusions of control, outside manipulation and influence,
or the feelings of passivity, which are connected with the
movements of the body or extremities, specific thoughts,
acting or feelings, delusional perception
hallucinated voices, which are commenting permanently the
behavior of the patient or they talk about him between
themselves, or the other types of hallucinatory voices,
coming from different parts of body
permanent delusions of different kind, which are
inappropriate and unacceptable in given culture

The Criteria of Diagnosis

e)
f)

g)
h)

i)

the lasting hallucination of every form

blocks or intrusion of thoughts into the flow of thinking and
resulting incoherence and irrelevance of speach, or
neologisms
catatonic behavior
the negative symptoms, for instance the expressed apathy,
poor speech, blunting and inappropriatness of emotional
reactions
expressed and conspicuous qualitative changes in patients
behavior, the loss of interests, hobbies, aimlesness,
inactivity, the loss of relations to others and social
withdrawal
Diagnosis of acute schizophorm disorder (F23.2) if the
conditions for diagnosis of schizophrenia are fulfilled, but
lasting less than one month
Diagnosis of schizoaffective disorder (F25) - if the
schizophrenic and affective symptoms are developing
together at the same time

F20-F29 Schizophrenia, Schizotypal

and Delusional Disorders

F20
F20.0
F20.1
F20.2
F20.3
F20.4
F20.5
F20.6
F20.8
F20.9

Schizophrenia
Paranoid schizophrenia
Hebephrenic schizophrenia
Catatonic schizophrenia
Undifferentiated schizophrenia
Post-schizophrenic depression
Residual schizophrenia
Simple schizophrenia
Other schizophrenia
Schizophrenia, unspecified

F20-F29 Schizophrenia, Schizotypal

F21

and Delusional Disorders

Schizotypal disorder

F22
F22.0
F22.8
F22.9

Persistent delusional disorders

Delusional disorder
Other persistent delusional disorders
Persistent delusional disorder, unspecified

F23
F23.1

Acute and transient psychotic disorders

Acute polymorphic psychotic disorder with
symptoms of schizophrenia
Acute schizophrenia-like psychotic disorder
Other acute predominantly delusional psychotic
disorders
Other acute and transient psychotic disorders
Acute and transient psychotic disorder,
unspecified

F23.2
F23.3
F23.8
F23.9

F20-F29 Schizophrenia, Schizotypal

and Delusional Disorders

F24

Induced delusional disorder

F25
F25.0
F25.1
F25.2
F25.8
F25.9

Schizoaffective disorders
Schizoaffective disorder, manic type
Schizoaffective disorder, depressive type
Schizoaffective disorder, mixed type
Other schizoaffective disorders
Schizoaffective disorder, unspecified

F28

Other nonorganic psychotic disorders

F29

Unspecified nonorganic psychosis

F20.0 Paranoid Schizophrenia

Paranoid schizophrenia is characterized

mainly by delusions of persecution,
feelings of passive or active control,
feelings of intrusion, and often by
megalomanic tendencies also. The
delusions are not usually systemized too
much, without tight logical connections
and are often combined with hallucinations
of different senses, mostly with hearing
voices.
Disturbances of affect, volition and
speech, and catatonic symptoms, are
either absent or relatively inconspicuous.

F20.1 Hebephrenic Schizophrenia

Hebephrenic schizophrenia is characterized by

disorganized thinking with blunted and
inappropriate emotions. It begins mostly in
adolescent age, the behavior is often bizarre. There
could appear mannerisms, grimacing, inappropriate
laugh and joking, pseudophilosophical brooding and
sudden impulsive reactions without external
stimulation. There is a tendency to social isolation.
Usually the prognosis is poor because of the rapid
development of "negative" symptoms, particularly
flattening of affect and loss of volition. Hebephrenia
should normally be diagnosed only in adolescents
or young adults.
Denoted also as disorganized schizophrenia

F20.2 Catatonic Schizophrenia

Catatonic schizophrenia is characterized

mainly by motoric activity, which might be
strongly increased (hypekinesis) or
decreased (stupor), or automatic obedience
and negativism.
We recognize two forms:
productive form which shows catatonic
excitement, extreme and often aggressive
activity. Treatment by neuroleptics or by
electroconvulsive therapy.
stuporose form characterized by general
inhibition of patients behavior or at least by
retardation and slowness, followed often by
mutism, negativism, fexibilitas cerea or by
stupor. The consciousness is not absent.

F20.3 Undifferentiated
Schizophrenia

Psychotic conditions meeting the general

diagnostic criteria for schizophrenia but
not conforming to any of the subtypes in
F20.0-F20.2, or exhibiting the features of
more than one of them without a clear
predominance of a particular set of
diagnostic characteristics.
This subgroup represents also the former
diagnosis of atypical schizophrenia.

F20.4 Postschizophrenic
Depression

A depressive episode, which may be

prolonged, arising in the aftermath of a
schizophrenic illness. Some schizophrenic
symptoms, either positive or negative,
must still be present but they no longer
dominate the clinical picture.
These depressive states are associated
with an increased risk of suicide.

F20.5 Residual Schizophrenia

A chronic stage in the development of

schizophrenia with clear succession from
the initial stage with one or more episodes
characterized by general criteria of
schizophrenia to the late stage with longlasting negative symptoms and
deterioration (not necessarily irreversible).

F20.6 Simple Schizophrenia

Simple schizophrenia is characterized by

early and slowly developing initial stage
with growing social isolation, withdrawal,
small activity, passivity, avolition and
dependence on the others.
The patients are indifferent, without any
initiative and volition. There is not
expressed the presence of hallucinations
and delusions.

F21 Schizotypal disorder

According to lCD-10 this disorder is

characterized by eccentric behavior and by
deviations of thinking and affectivity,
which are similar to that occurring in
schizophrenia, but without psychotic
features and expressed symptoms of
schizophrenia of any type.

F22 Persistent Delusional

Disorders

Includes a variety of disorders in which

long-standing delusions constitute the
only, or the most conspicuous, clinical
characteristic and which cannot be
classified as organic, schizophrenic or
affective.
Their origin is probably heterogeneous,
but it seems, that there is some relation to
schizophrenia.

F22.0 Delusional Disorder

A disorder characterized by the

development of one delusion or of the
group of similar related delusions, which
are persisting unusually long, very often
for the whole life.
Other psychopathological symptoms
hallucinations, intrusion of thoughts etc.
are not present and are excluding this
diagnosis.
It begins usually in the middle age.

F23 Acute and Transient

Psychotic Disorders

The criteria should be the following

features:

acute beginning (to two weeks)

presence of typical symptoms (quickly
changing polymorphic symptoms)
presence of typical schizophrenic symptoms.

Complete recovery usually occurs within a

few months, often within a few weeks or
even days.
The disorder may or may not be
associated with acute stress, defined as
usually stressful events preceding the
onset by one to two weeks.

F24 Induced Delusional Disorder

A delusional disorder shared by two or

more people with close emotional links.
Only one of the people suffers from a
genuine psychotic disorder; the delusions
are induced in the other(s) and usually
disappear when the people are separated.
The psychotic disorder of the dominant
member of this dyad is mainly, but not
necessarily, of schizophrenic type. The
original delusions of dominant member
and his partner are usually chronic, either
persecutory or megalomanic.

F25 Schizoaffective Disorders

Episodic disorders in which both affective and

schizophrenic symptoms are prominent (during the
same episode of the illness or at least during few
days) but which do not justify a diagnosis of either
schizophrenia or depressive or manic episodes.
Patients suffering from periodic schizoaffective
disorders, especially with manic symptoms, have
usually good prognosis with full remissions without
any remaining defects.
They are divided in different subgroups:

F25.0
F25.1
F25.2
F25.8
F25.9

Schizoaffective disorder, manic type

Schizoaffective disorder, depressive type
Schizoaffective disorder, mixed type
Other schizoaffective disorders
Schizoaffective disorder, unspecified

Genetics of Schizophrenia

Many psychiatric disorders are

multifactorial (caused by the interaction of
external and genetic factors) and from the
genetic point of view very often
polygenically determined.
Relative risk for schizophrenia is around:

1% for normal population

5.6% for parents
10.1% for siblings
12.8% for children

Etiology of Schizophrenia

The etiology and pathogenesis of

schizophrenia is not known
It is accepted, that schizophrenia is
the group of schizophrenias which
origin is multifactorial:
internal factors genetic, inborn,
biochemical
external factors trauma, infection of
CNS, stress

Etiology of Schizophrenia Dopamine Hypothesis

The most influential and plausible are the

hypotheses, based on the supposed disorder of
neurotransmission in the brain, derived mainly from
1. the effects of antipsychotic drugs that have in common the
ability to inhibit the dopaminergic system by blocking action
of dopamine in the brain
2. dopamine-releasing drugs (amphetamine, mescaline,
diethyl amide of lysergic acid - LSD) that can induce state
closely resembling paranoid schizophrenia

Classical dopamine hypothesis of schizophrenia :

Psychotic symptoms are related to dopaminergic
hyperactivity in the brain. Hyperactivity of
dopaminergic systems during schizophrenia is result
of increased sensitivity and density of dopamine D2
receptors in the different parts of the brain.

Etiology of Schizophrenia Contemporary Models

Dopamine hypothesis revisited: various

neurotransmitter systems probably takes place in
the etiology of schizophrenia (norepinephric,
serotonergic, glutamatergic, some peptidergic
systems); based on effects of atypical
antipsychotics especially.
Contemporary models of schizophrenia
conceptualize it as a neurocognitive disorder, with
the various signs and symptoms reflecting the
downstream effects of a more fundamental
cognitive deficit:
the symptoms of schizophrenia arise from cognitive
dysmetria (Nancy C. Andreasen)
concept of schizophrenia as a neurodevelopmental
disorder (Daniel R. Weinberger)

Etiology of Schizophrenia Neurodevelopmental Model

Neurodevelopmental model supposes in

schizophrenia the presence of silent lesion in the
brain, mostly in the parts, important for the
development of integration (frontal, parietal and
temporal), which is caused by different factors
(genetic, inborn, infection, trauma...) during very
early development of the brain in prenatal or early
postnatal period of life.
It does not interfere too much with the basic brain
functioning in early years, but expresses itself in
the time, when the subject is stressed by
demands of growing needs for integration, during
formative years in adolescence and young
adulthood.

Treatment of Schizophrenia

The acute psychotic schizophrenic patients will

respond usually to antipsychotic medication.
According to current consensus we use in the first
line therapy the newer atypical antipsychotics,
because their use is not complicated by appearance
of extrapyramidal side-effects, or these are much
lower than with classical antipsychotics.
conventional
antipsychotics
(classical
neuroleptics)
atypical
antipsychotics

chlorpromazine, chlorprotixene, clopenthixole,

levopromazine, periciazine, thioridazine
droperidole, flupentixol, fluphenazine,
fluspirilene, haloperidol, melperone,
oxyprothepine, penfluridol, perphenazine,
pimozide, prochlorperazine, trifluoperazine
amisulpiride, clozapine, olanzapine,
quetiapine, risperidone, sertindole, sulpiride

Positive vs. negative symptoms

Positive symptoms
Delusions
Hallucinations
Behavioral dyscontrol
Thought disorder

Negative symptoms
(Remember
Andreasens As)
Affective flattening
Alogia
Avolition
Anhedonia
Attentional impairment

Psychotic Disorders
Onset

Symptoms

Schizophrenia

Usually
insidious

Delusional
disorder

Varies
Delusions
(usually
only
insidious)
Sudden
Varies

Brief
psychotic
disorder

Many

Course

Duration

Chronic

>6 months

Chronic

>1 mo.

Limited

<1 mo.

Psychosocial Factors

Expressed emotion
Stressful life events
Low socioeconomic class
Limited social network

Some factors rejected as causal

Schizophrenogenic Mother

Skewed family structure

Genetic factors:
(The evidence mounts)

Monozygotic twins (31%-78%) vs

dizygotic twins
4-9% risk in first degree relatives of
schizophrenics
Adoption studies
Linkage, molecular studies

Genetics of Schizophrenia:
The take-home message

Vulnerability to schizophrenia is likely

inherited
Heritability is probably 60-90%
Schizophrenia probably involves
dysfunction of many genes

Anatomical abnormalities

Enlargement of lateral ventricles

Smaller than normal total brain
volume
Cortical atrophy
Widening of third ventricle
Smaller hippocampus

Physiologic studies:
PET and SPECT

Generally normal global cerebral flow

Hypofrontality
Failure to activate dorsolateral
prefrontal cortex (problem-solving,
adaptation, coping with changes)

Biochemical factors:
The dopamine hypothesis

All typical antipsychotics block D2

with varying affinities
Dopamine agonists can precipitate a
psychosis
Amphetamines
Cocaine
L-dopa

Dopamine systems
Cell bodies

Projections Functions

Clinical
implications

Nigrostriatal
Mesolimbic

Substantia
Nigra

Caudate
and
putamen

Movement

Extrapyramidal
symptoms, dystonias,
Tardive dyskinesia

Ventral
tegmental
area, subst.
nigra

Accumbens
amygdala
Olfactory
tubercle

Emotions, Positive symptoms

affect,
memory

Mesocortical

Ventral
tegmental
area

Prefrontal
Cortex

Thought,
volition,
memory

Blockade here can

worsen negative
symptoms.

Typical Neuroleptics

Low potency:

Chlorpromazine
Thioridazine
Mesoridazine

High potency:

Haloperidol
Fluphenazine
Thiothixene
Loxapine (mid)

Neuroleptic (typicals):
side effects

Acute dystonia
Parkinsonian side effects (EPS)
Akathisia
Tardive dyskinesia
Sedation, orthostasis, QTC
prolongation, anticholinergic, lower
seizure threshold, increased prolactin

Atypical Antipsychotics:

Risperidone
Olanzapine
Quetiapine
Clozapine
Ziprasidone
Aripiprazole (new-partial DA agonist)

Atypical antipsychotics:

Broader spectrum of receptor activity

(Serotonin, dopamine, GABA)
May be better at alleviating negative
symptoms and cognitive dysfunction
Clozaril (clozapine) associated with
agranulocytosis, seizures

Atypical Antipsychotics: Side

Effects

Sedation
Hyperglycemia, new-onset diabetes
Anticholinergic effects
Less prolactin elevation
QTC prolongation
Some EPS
Increased lipids

Psychosocial Treatment

Education, compliance #1
Hospitalize for acute loss of
functioning
Outpatient treatment is rehabilitative
Psychoanalysis, exploratory therapies
have limited value
Families should be involved

Genetics

Greatest risk factor is having a

relative with SCZ
70% of the heritability of
schizophrenia is genetic
MZ twin 48% risk; DZ twin 17%
Child of one parent with SCZ 13%
Child of two parents with SCZ 46%

Genetics

Adoption studies indicate that

heritability rates are similar even if
adopted away
Probably polygenic/multifactorial
model
No clear gene responsible although
interest in various genes

Neurodevelopmental Theories

Hypothesis states that impaired

foetal or neonatal brain development
many sow the seeds of the onset of
psychotic symptoms in later life
Patients with SCZ have lower than
average IQ, often subtle
psychomotor, behaviourla, and social
abnormalities

Neurodevelopmental Theories

Patients with SCZ have more

developmental structural brain
abnormalities
Soft neurological signs
Increase in craniofacial and
dermatoglyphic abnormalities
More obstetric complications
recorded
Exposure to influenza virus?

Psychological Theories

Freud delusions as a way of

making sense of the external world
Klein failure to resolve the
paranoid/schizoid position
Cameron loss of conceptual
boundaries
Goldstein concrete thinking
Difficulties in filtering senory input?

Familial/Social Theories

Probably important in precipitating

schizophrenia than causing it
Lidz marital schism/marital skew
Bateson double bind
High expressed emotion
It has been hypothesised that life evetns
could precipitate SCZ more life events in
the 3 weeks prior to episode than with
healthy controls

Prognosis

22% have one episode and no

residual impairment
35% have recurrent episodes and no
residual impairment
8% have recurrent epsiodes and
develop significant non-progressive
impairment
35% have recurrent episodes and
develop significant progressive
impairment

Treatment

May require admission if acutely

disturbed or present a risk to self or
others
Admission may be useful in
assessment
Essential to assess suicide risk as
there is a mortality of about 10%
from suicide in SCZ
May require involuntary detention in
some cases

Treatment contd.

Antipsychotic drugs are mainstay of

treatment
Generally atypicals are first-line
treatment eg olanzapine,
respiridone, amisulpiride
May require depot injection
Side effects of typicals can be
stigmatising
Side effects of atypicals screen for
DM

Treatment contd.

Atypicals have fewer extra-pyramidal

side effects and tend to be better for
negative symptoms that typicals
Initial management may include use
of sedative medication such as
lorazepam
IM medication may be required in a
very disturbed, involuntary patient

Treatment contd.

Maintenance treatment generally

maintenance on one medication
Compliance may be a significant
problem because of long-term nature
of treatment and lack of insight

Treatment contd.

Psychosocial treatment

Education of patient and carers

Reduction of high expressed emotion shown
to affect relapse rates
Cognitive behavioural therapy controversial
Rehabilitation
Self help Schizophrenia Ireland

Prognosis

22% have one episode and no

residual impairment
35% have recurrent episodes and no
residual impairment
8% have recurrent epsiodes and
develop significant non-progressive
impairment
35% have recurrent episodes and
develop significant progressive
impairment

Prognosis contd.

The majority therefore do not

recover fully
Suicide rate is up to 13%
Little evidence that anitpsychotic
have altered the course of illness for
most patients
However, evidence that prolonged
psychosis which is untreated has a
bad prognosis

Prognosis contd.

Good outcome is associated with:

Female
Older age of onset
Married
Higher SEG
Living in a developing (as opposed to developed)
country
Good premorbid personality
No previous psych history
Good education and employment record
Acute onset, affective symptoms, good
compliance with meds

Prognosis contd.

Some of the predictors of outcome

are the consequence of a less severe
illness
Predicting risk of suicide

Acute exacerbation of psychosis

Depressive symptoms
History of attempted suicide