Schizophrenia

Saraswati Dhungana
Department of Psychiatry, IOM
June 13, 2025
 Content
• Introduction
• Clinical features and diagnosis
• Classification
• Epidemiology
• Aetiology
• Course and Prognosis
• Management
 Introduction
• History
– Emil Kraepelin, German psychiatrist (1887)
"dementia praecox"
– Eugen Bleuler (1911) coined the term
"schizophrenia”
– Derived from the Greek roots
schizo (split) and phrene (mind)
 Introduction
• Bleuler’s Four A’s:
₋ Association (thought disorder)
₋ Affect (emotional disturbance)
₋ Ambivalence (inability to make or follow
through on decisions)
₋ Autism (withdrawal from reality)
 Introduction

• The broad category of schizophrenia includes a

set of disorders in which individuals experience
distorted perception of reality and

• impairment in thinking, behavior, affect, and

motivation
 Clinical features
• Positive symptoms
• Negative symptoms
• Cognitive symptoms
• Mood symptoms
• Loss of insight
 Clinical Features

Positive Symptoms Negative Symptoms

 Delusions  Affective flattening
 Hallucinations  Anhedonia
 Disorganization  Alogia
 Catatonia  Avolition
 Social withdrawal
 Clinical Features
• Mood Symptoms
–Anxiety
–Depression, suicidality
–Agitation, hostility

• Cognitive Deficits
–Attention, memory, executive functions
 Schneider’s first rank symptoms
• Audible thoughts
• Voices heard arguing
• Voices commenting on one’s action
• Thought withdrawal
• Thought insertion
• Thought diffusion or broadcasting
• Made feelings, impulses, volition or acts
• Somatic passivity, Delusional perception
 ICD-10 criteria for diagnosis
• 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, or the feelings of passivity,

connected with the movements of the body, specific
thoughts, acting or feelings, delusional perception
 ICD-10 Criteria (a-d)
c) Hallucinated voices, which are commenting,
or they talk about him/her between themselves,
or voices coming from different parts of body

d) Permanent delusions which are inappropriate

and unacceptable in given culture
 ICD-10 criteria (e-i)
e) The lasting hallucination of every form

f) Blocks or intrusion of thoughts into the flow of

thinking, incoherence of speech, or neologisms

g) Catatonic behavior
 ICD-10 criteria (e-i)
h) The negative symptoms: apathy, poor speech,
blunting and inappropriateness of emotional
reactions

i) Qualitative changes in patient’s behavior, loss

of interests, hobbies, aimlessness, inactivity, the
loss of relations to others and social withdrawal
 Epidemiology
• Lifetime prevalence: 0.5 – 1.0% (DSM-5: 0.3 -
0.7%)
• Average age of onset:
– Males: 20–28 years ; Females: 26–32 years
– Range: 15 to 50’s/60’s
• Male = female
• Leads to suicide in ~10% of cases, especially in
first decade of illness
 Etiology
• Biological
• Psychological
• Social
 Biological theories
• Genetic

– The concordance rate for monozygotic

twins is 46% and for dizygotic twins is 14%
– First degree relative with the condition, risk
increases by 8-10 fold
 Biological theories
• Biochemical
– Mesolimbic-mesocortical pathway

– Functional increase of dopamine

– Other neurotransmitters such as serotonin
(especially 5-HT2 receptors), GABA and
acetylcholine, Glutamate
Image taken from Four Major Dopaminergic Pathways & Association with Schizophrenia - Bepharco
 Psychological

• Increased number of stressful life events

before the onset or relapse probably

• Increased expressed emotions (such as

hostility, critical comments, emotional over-
involvement) in the family can lead to an
early relapse
 Psychological
• Marital schism or skew

• Double-bind theory

• Psychoanalytical Theories:
₋ Regression to the preoral (and oral) stage of psychosexual
development
₋ Defense mechanisms of denial, projection, and reaction
formation
 Sociocultural Theories
• ‘Downward social drift’
– found to be more common in lower
socioeconomic status in some studies

• Higher rates of schizophrenia found among

migrants
 Classification
ICD-10 classification
• F20-F29 Schizophrenia, Schizotypal and
Delusional Disorders
– F20 Schizophrenia
• F20.0 Paranoid schizophrenia
• F20.1 Hebephrenic schizophrenia
• F20.2 Catatonic schizophrenia
 ICD-10 classification contd..
• 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
 Subtypes

F20.0 Paranoid Schizophrenia

• Mainly delusions of persecution, feelings of
passive or active control, feelings of intrusion
• Combined with hearing of voices
• Negative, and catatonic symptoms, are either
absent or relatively inconspicuous
 Subtypes
F20.1 Hebephrenic Schizophrenia (Disorganized)

• It begins mostly in adolescent age, the behavior is

often bizarre
• Disorganized thinking with blunted and inappropriate
emotions
• Negative symptoms, particularly flattening of affect
and loss of volition
 Subtypes
F20.2 Catatonic Schizophrenia
•Two forms:
– productive form — which shows catatonic
excitement, extreme and often aggressive
activity
– stuporose form — general inhibition of
patient’s behavior followed often by
mutism, negativism, fexibilitas cerea
 Subtypes
F20.3 Undifferentiated Schizophrenia
• 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
 Subtypes
20.4 Postschizophrenic Depression
•Depressive episode, arising in the aftermath of
a schizophrenic illness
•Some schizophrenic symptoms, either positive
or negative , may be present
 Subtypes
F20.5 Residual Schizophrenia

•A chronic stage in the development of

schizophrenia with long-lasting negative
symptoms and deterioration (not necessarily
irreversible)
 Subtypes
F20.6 Simple Schizophrenia
•Early and slowly developing initial stage with
growing social isolation, withdrawal, small
activity, passivity, avolition and dependence on
the others
•There is not expressed presence of
hallucinations and delusions
 Schizophrenia like disorders
• F21 Schizotypal disorder
• F22 Persistent delusional disorder
• F23 Acute and transient psychotic disorder
• F24 Induced delusional disorder
• F25 Schizoaffective disorder
• F28 Other non-organic psychotic disorder
• F29 Unspecified non-organic psychosis
 Course
• Complete remission (27%)
• Remission with minor residual symptoms
(22%)
• Intermediate outcome (24%)
• Severe disability (18%)
• Unstable or uncertain outcome (9%)
 Management
Acute phase Stabilization phase Stable or Maintenance
phase

Acute psychotic symptoms Lasts around 6 months Stage of remission

4-8 weeks after acute control Focus on improving
function

Indications for admission

Diagnostic purpose Self and others safety Inability to take care of

basic needs and self

Stabilization of medication Grossly disorganized or

inappropriate behavior
 Management
Somatic treatment Psychological treatment

• Antipsychotics: mainstay • Family Intervention

• Electroconvulsive therapy • Cognitive behavioral
therapy
 Antipsychotics
• Major class for treatment of psychosis
in schizophrenia and psychosis due to any cause
• Use expanded over recent years
 Classification

Type of receptor
Potency
binding
 Receptor binding
First generation/Typical Second generation/Atypical
(1950s) (1990s)
 Vary in receptor affinity (5HT2A)
 Block D2 receptors Serotonin dopamine antagonists
Dopamine receptor  Fewer EPS
 Unclear if better for negative symptoms
antagonists
 Initially thought more effective and safer
 Reduce positive symptoms  CATIE trial
and agitation and aggression  Metabolic side effects: increased
 Elevated prolactin levels blood pressure, high blood sugar,
excess body fat around the waist,
 Extrapyramidal symptoms and abnormal cholesterol or
triglyceride levels occurring
(EPS) together
 Neuroleptic malignant
syndrome
 Based on potency
Low potency Medium potency High potency

Chlorpromazine Perphenazine Haloperidol

Clozapine Zuclopenthixol Fluphenazine

Quetiapine Olanzapine Risperidone

Amisulpride Aripiprazole Paliperidone

Efficacy

D2 receptor
occupancy
and clinical
effects
Pathway Function Effect of dopamine
blockade

1. Nigrostriatal Sensory stimuli and Extrapyramidal symptoms

(Substantia nigra movement
striatum)

2. Mesolimbic Emotion, reward, positive Reduction in positive

(VTANA) symptoms symptoms

3. Mesocortical Cognitive and emotional Reduction of negative

(VTAPFC) behavior symptoms

4. Tuberoinfundibular Regulation of Raised prolactin level

(Tuberal region of hypothalamic-pituitary
hypothalamus to endocrine system
median eminence)
 Adverse effects
 Most of schizophrenia drugs side effects comes from blocking
D2 receptors in pathways other than mesolimbic-mesocortical
 Plus blockade of other receptors (muscarinic, α-adrenergic,
and H1)
 If we avoid blocking D2 , we avoid these side effects
 Dopamine Receptors
 There are at least five subtypes of receptors:
D 1, D 2, D 3, D 4, D 5
 Adverse effects contd…
Central nervous system
1. Sedation, drowsiness, fatigue
2. Extrapyramidal effects Early (Acute dystonia, akathisia,
parkinsonism), Late (Tardive dyskinesia)

Neuroleptic Malignant Tardive Dyskinesia (Late serious)

Syndrome
Rare but life threatening • It is a disorder of involuntary movements
Symptoms are muscle (choreoathetoid movements of lips,
rigidity, autonomic tongue, face, jaws, and limbs )
instability, and high fever
• Choreoathetosis: combination of chorea
(irregular migrating contractions) and
athetosis (twisting)
 Adverse effects contd…
Autonomic nervous system
: Antiadrenergic Effects : Anticholinergic Effects

 Blurred vision
 Postural hypotension  Dry mouth
 Impotence  Urinary retention
 Failure of ejaculation  Constipation→
 Chlopromazine (typical) Such as with:
 Thioridazine (typical) Chlorpromazine (typical), Clozapine
(atypical)

Endocrine effects Miscellaneous

 Amenorrhoea  Weight gain
 Gyanecomastia  Obstructive jaundice
 Infertility  Retinal deposits
 Sexual dysfunction  Granular deposits in cornea

:Clozapine specific effects

Agranulocytosis (life threating) Seizures

About 1-2% -
Usually happen after 6-18 weeks -
Weekly WBC is mandatory -
 Therapeutic uses
Psychiatric Non-psychiatric
Schizophrenia ( primary Nausea and vomiting
indication) (prochlorperazine and
Acute mania benzquinamide) Only used
Bipolar affective disorder- as antiemetics
during the manic phase Pruritis (Itching because of
anti-histamine effect)
Preoperative sedation (rare
use)