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
P
S
Y
C
H
O
S
I
S
Mood disorders
Schizophrenia
spectrum
disorders
organic
mental
disorders
Substance
induced
Delirium
Dementia
Amnestic d/o
Functional
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 lCD-
10, 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 Positive
Alogia Hallucinations
Affective flattening Delusions
Avolition-apathy Bizarre behaviour
Anhedonia-asociality 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) the hearing of own thoughts, the feelings of thought
withdrawal, thought insertion, or thought broadcasting
b) 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
c) 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
d) permanent delusions of different kind, which are
inappropriate and unacceptable in given culture
The Criteria of Diagnosis
e) the lasting hallucination of every form
f) blocks or intrusion of thoughts into the flow of thinking and
resulting incoherence and irrelevance of speach, or
neologisms
g) catatonic behavior
h) the negative symptoms, for instance the expressed
apathy, poor speech, blunting and inappropriatness of
emotional reactions
i) 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 Schizophrenia
F20.0 Paranoid schizophrenia
F20.1 Hebephrenic schizophrenia
F20.2 Catatonic schizophrenia
F20.3 Undifferentiated schizophrenia
F20.4 Post-schizophrenic depression
F20.5 Residual schizophrenia
F20.6 Simple schizophrenia
F20.8 Other schizophrenia
F20.9 Schizophrenia, unspecified
F20-F29 Schizophrenia, Schizotypal
and Delusional Disorders
F21 Schizotypal disorder

F22 Persistent delusional disorders
F22.0 Delusional disorder
F22.8 Other persistent delusional disorders
F22.9 Persistent delusional disorder, unspecified

F23 Acute and transient psychotic disorders
F23.1 Acute polymorphic psychotic disorder with
symptoms of schizophrenia
F23.2 Acute schizophrenia-like psychotic disorder
F23.3 Other acute predominantly delusional
psychotic disorders
F23.8 Other acute and transient psychotic disorders
F23.9 Acute and transient psychotic disorder,
unspecified
F20-F29 Schizophrenia, Schizotypal
and Delusional Disorders
F24 Induced delusional disorder

F25 Schizoaffective disorders
F25.0 Schizoaffective disorder, manic type
F25.1 Schizoaffective disorder, depressive type
F25.2 Schizoaffective disorder, mixed type
F25.8 Other schizoaffective disorders
F25.9 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 long-
lasting 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 Schizoaffective disorder, manic type
F25.1 Schizoaffective disorder, depressive type
F25.2 Schizoaffective disorder, mixed type
F25.8 Other schizoaffective disorders
F25.9 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)
chlorpromazine, chlorprotixene, clopenthixole,
levopromazine, periciazine, thioridazine
droperidole, flupentixol, fluphenazine,
fluspirilene, haloperidol, melperone,
oxyprothepine, penfluridol, perphenazine,
pimozide, prochlorperazine, trifluoperazine
atypical
antipsychotics

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
Schizo-
phrenia
Usually
insidious
Many Chronic >6 months
Delusional
disorder
Varies
(usually
insidious)
Delusions
only
Chronic >1 mo.
Brief
psychotic
disorder
Sudden Varies Limited <1 mo.
Onset
Symptoms Course Duration
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
Nigro-
striatal
Substantia
Nigra
Caudate
and
putamen
Move-
ment
Extrapyramidal
symptoms, dystonias,
Tardive dyskinesia
Meso-
limbic
Ventral
tegmental
area, subst.
nigra
Accumbens
amygdala
Olfactory
tubercle
Emotions,
affect,
memory
Positive symptoms
Meso-
cortical
Ventral
tegmental
area
Prefrontal
Cortex
Thought,
volition,
memory
Blockade here can
worsen negative
symptoms.
Cell bodies Projections
Functions
Clinical
implications
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