SEMEY STATE MEDICAL UNIVERSITY

Department of Psychiatry
Topic
SCHIZOPHRENIA

Raja Ali Hassan

Schizophrenia
Schizophrenia
 A serious mental disorder characterized by disordered
thoughts, delusions, hallucinations, and often bizarre
behaviors
 Afflicts ~1% of population
 Probably the most misused psychological term – literally
means “split mind”, so often confused with multiple
personality disorder
 Positive symptoms – symptoms evident by their presence
 Thought disorders – disorganized, irrational thinking (most
important symptom)
 Delusions – a belief that is clearly in contradiction to reality
 Persecution – false beliefs that others are plotting against oneself
 Grandeur – false beliefs in one’s own power
 Control – belief that one is being controlled by others
 Hallucinations – perception of a nonexistent object or event
Schizophrenia
 Negative symptoms – characterized by the absence of
behaviors that are normally present
 Flattened emotional response
 Poverty of speech
 Lack of initiative and persistence
 Inability to experience pleasure
 Social withdrawal
 Heritability
 Both adoption and twin studies indicate that schizophrenia is a
heritable trait
 If there is a “schizophrenia gene”, then it must be triggered by
some type of env’tal event
 Study shows that higher paternal age is positively correlated
with diagnosis of schizophrenia
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
What causes schizophrenia?

• There is no one accepted cause for schizophrenia.

• Interactions between genetic predisposition and environmental influences
disrupt neuro-developmental processes leading first to pre-morbid symptoms and
then to the onset and progression of schizophrenia.

• Heredity  schizophrenia is genetically linked

 more than one gene may predispose people to it
 there is currently no reliable way to predict
whether a person will develop the disease.

• Environment  pregnancy and delivery complications

 childhood and prenatal virus infection
 urban birth and residence
 psychosocial factors (dysfunctional family environment)

• Changes in brain structure  enlarged ventricles

 reduced regional cerebral volumes
 reduced activity in the temporal lobes
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 multi-factorial:
 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 (nor-epinephric, 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.
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
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
Hallucinations
 Sensory experiences in the absence of any
stimulation from the environment
 Any sensory modality may be involved:
auditory (hearing); visual (seeing);
olfactory (smelling); tactile (feeling);
gustatory (tasting)
 Auditory hallucinations are most common
Common auditory hallucinations in
schizophrenia

 Hearing own thoughts spoken by another

voice
 Hearing voices that are arguing
 Hearing voices commenting on one’s own
behavior
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
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
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

Schizophrenia as a neurological
disorder
 Whereas the positive symptoms are unique to
schizophrenia, the negative symptoms are similar to those
produced by brain damage caused by several different
means
 Brain abnormalities in schizophrenia
 Patients with schizophrenia exhibit neurological symptoms
that suggest brain damage (e.g. poor control of eye
movements, unusual facial expressions)
 This suggests that schizophrenia may be associated with brain
damage of some kind
 MRI and CT studies have found loss of brain tissue in patients
with schizophrenia
 Relative size of lateral ventricles was more than twice the size of
control subjects
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.
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

Catatonic Schizophrenia
 Catatonic schizophrenia is characterized mainly
by motor activity, which might be strongly
increased (hyperkinesis) 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
patient’s behavior or at least by retardation and
slowness, followed often by mutism, negativism,
fexibilitas cerea or by stupor. The consciousness is not
absent.
Undifferentiated Schizophrenia
 Psychotic conditions meeting the general
diagnostic criteria for schizophrenia but not
conforming to any of the subtypes, 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.
 Post-schizophrenic 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.
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).
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.
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.
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.
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
Major Affective Disorders
 Affect – refers to feelings or emotions
 Major affective disorders – a serious mood disorder;
includes unipolar and bipolar disorder
 Bipolar disorder – characterized by cyclical periods of mania
(extreme elation) and depression (extreme despair);
episodes of mania generally shorter than episodes of
depression
 Unipolar depression – consists of unremitting depression or
periods of depression that do not alternate with periods of
mania
 Depression causes very little energy, crying, inability to
experience pleasure, disturbed sleep, depressed bodily
functions
 Mania involves sense of euphoria, nonstop speech and
motor activity, easily angered, go without sleep
Major Affective Disorders
 Heritability
 The tendency to develop a major affective disorder is heritable
 A single dominant gene is responsible for susceptibility to
developing bipolar disorder
 Physiological treatments
 MAO inhibitors
 Drugs (e.g. Iproniazid) that inhibit the activity of MAO, the enzyme
that destroys excess monoamine transmitter substance within
terminal buttons, increase the release of DA, NE and 5-HT
 Have serious side effects, e.g. cheese effect with pressor amines
 Tricyclic antidepressants
 Inhibit the reuptake of 5-HT and NE by terminal buttons
 This keeps the NT in contact with the postsynaptic receptor, thus
prolonging the postsynaptic potentials
 Specific serotonin reuptake inhibitors (SSRI)
 Inhibit reuptake of 5-HT
 Widely prescribed for depression and for symptoms of OCD and
social phobia
Major Affective Disorders
 Physiological treatments
 Electroconvulsive therapy (ECT)
 Electrodes placed on patients scalp deliver a jolt of electricity to
trigger a seizure
 Most effective with mania and depression
 Effects are rapid, as compared to drugs
 Lithium
 Most effective in treating the manic phase of bipolar disorder
 Does not suppress normal feelings of emotion
 Does not impair intellectual processes
 Does have some side effects, including hand tremors, weight gain,
excessive urine production and thirst
 Some patients with bipolar disorder have trouble continuing with
medication
 Those who cannot tolerate side effects can take carbamazepine, an
anti-seizure medication
Major Affective Disorders
 Role of monoamines
 Monoamine hypothesis: hypothesis that states that depression
is caused by a low level of activity of one or more
monoaminergic synapses
 Since the symptoms of depression do not respond to potent
DA agonists (e.g. amphetamine or cocaine), researchers have
focused on NE and 5-HT
 Depression can be caused by monoamine antagonists
 e.g. reserpine
 Suicidal depression is related to decreased CSF levels of 5-
HIAA, a metabolite of 5-HT that is produced when MAO breaks
it down
 Families of subjects with low levels of 5-HIAA were more likely
to include people with depression
 Suggests that 5-HT metabolism or release is genetically controlled
and is linked to depression
Major Affective Disorders
 Role of monoamines
 Tryptophan depletion procedure
 Depressed patients currently taking medication
 Gave low-tryptophan diet, follwed by an amino acid “cocktail”,
which would inhibit what little tryptophan was left from entering
the brain
 Tryptophan depletion caused most of the patients to relapse back
into depression
 However, recovered after resuming normal diet
 This has no effect on healthy, non-depressed subjects, but does
lower the mood of people with a family history of affective
disorders
Major Affective Disorders
 A role for Substance P?
 A peptide secreted as a NT and neuromodulator in several
regions of the brain
 May be involved in emotional behavior, the response to stress,
and the symptoms of depression
 Long-term admin of antidepressants cause a reduction of
substance P levels in several regions of the brain
 MK-869, a drug that blocks the receptor for substance P (NK1)
shows a reduction in depressive symptoms
 Substance P antagonists appear to act independently of drugs
that reduce depression by blocking the reuptake of 5-HT and
NE
Major Affective Disorders
 Evidence for brain abnormalities
 Studies have found abnormalities in the prefrontal cortex,
basal ganglia, and cerebellum of patients with unipolar
depression, and abnormalities of the cerebellum in those with
bipolar disorder
 Found in young patients, which suggests the presence of a
developmental abnormality or a degenerative process that
occurs early in life
 Repeated episodes of depression and mania caused an
increase in the size of the lateral ventricles
 The amygdala and several regions of the prefrontal cortex play
a role in the development of depression
 Activity of amygdala of depressed patients was correlated with the
severity of their depression
 Orbitofrontal cortex generally more active in depressed patients
 Subgenual prefrontal cortex shows a lower level of activation in
depressed patients; activity in this region is increased during manic
episodes
Major Affective Disorders
 Evidence for brain abnormalities
 Silent cerebral infarctions
 A small cerebrovascular accident (stroke) that causes minor brain
damage without producing obvious neurological symptoms
 Appears to be a major cause of late-onset depression (first occurs
later in life)
 Risk factors are similar for stroke (e.g. smoking, hypertension)
Major Affective Disorders
 Role of circadian rhythms
 One of the most prominent symptoms of depression is
disordered sleep
 Sleep of depressed individuals is shallow, Stages 3 & 4 are
reduced, Stage 1 is increased
 REM sleep occurs earlier
 Selective deprivation of REM sleep alleviates depression
 The effect occurs slowly like that of drugs
 Other treatments for depression suppress REM sleep, suggesting
that REM sleep and mood may be correlated
 Successful ECT treatments suppress REM sleep in depressed
patients
 Total sleep deprivation produces immediate effects
 Perhaps, during sleep a substance is produced that has a
depressogenic effect
 Depressed patients whose moods fluctuate more often will
benefit from sleep deprivation more
Major Affective Disorders
 Role of Zeitgebers
 Seasonal affective disorder – a mood disorder characterized by
depression, lethargy, sleep disturbances, and craving for
carbohydrates during the winter season when days are short
 Summer depression – a mood disorder characterized by
depression, sleep disturbances, and loss of appetite
 Seasonal affective disorder appears to have a genetic basis
 Molecular genetic studies suggest that seasonal affective disorder
may be linked to genes involved in production of the 5-HT
transporter and the 5-HT2A receptor
 SAD can be treated with phototherapy, treatment of exposing
people to bright light for several hours a day
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 patient’s
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
 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 extra-pyramidal side-effects, or
these are much lower than with classical antipsychotics.

chlorpromazine, chlorprotixene, clopenthixole,

levopromazine, periciazine, thioridazine
conventional
antipsychotics
(classical droperidole, flupentixol, fluphenazine, fluspirilene,
neuroleptics) haloperidol, melperone, oxyprothepine,
penfluridol, perphenazine, pimozide,
prochlorperazine, trifluoperazine
atypical amisulpiride, clozapine, olanzapine, quetiapine,
antipsychotics risperidone, sertindole, sulpiride