Schizophrenia according to standard book of mbbs final year

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Schizophrenia

Source: Kaplan & Sadock's Synopsis of Psychiatry (Standard MBBS Final Year Psychiatry Textbook)

Definition

Schizophrenia is a chronic, severe psychiatric disorder characterized by a disturbance in perception, thought, affect, and behavior, persisting for at least 6 months (DSM-5) or 1 month (ICD-10), with significant functional impairment. It is the prototypic psychotic disorder.

Epidemiology

Parameter	Details
Lifetime prevalence	~1% worldwide
Age of onset	Late adolescence to early adulthood (peak: males 15-25 yrs; females 25-35 yrs)
Sex	Equal prevalence; women have later onset and better prognosis
Late onset (>45 yrs)	More common in women; often paranoid subtype
Marital status	Higher rates in unmarried, divorced, widowed
Socioeconomic	More prevalent in lower socioeconomic groups (downward drift)

Etiology

1. Genetic Factors

Heritability estimated at 60-80%
Concordance in monozygotic twins: ~50% (4-5x higher than dizygotic twins ~12%)
First-degree relatives: ~10% risk (vs. 1% general population)
Advanced paternal age is a risk factor (epigenetic damage to sperm)
Key genes: COMT (catechol-O-methyltransferase) polymorphism, genes involved in glutamate signaling
22q11.2 microdeletion (DiGeorge/velocardiofacial syndrome) - rare high-penetrance variant associated with psychosis
GWAS studies: hundreds of common alleles with small individual effects

2. Neurotransmitter Hypotheses

Hypothesis	Detail
Dopamine hypothesis	Excess dopaminergic activity (mesolimbic) causes positive symptoms; reduced D2 activity in prefrontal cortex causes negative symptoms
Glutamate (NMDA) hypothesis	NMDA receptor hypofunction - explains why PCP/ketamine (NMDA antagonists) cause schizophrenia-like symptoms
Serotonin hypothesis	5-HT2A receptors involved - basis for atypical antipsychotics (block both D2 + 5-HT2A)

3. Brain Structure and Neuroimaging

CT/MRI: Enlarged lateral and third ventricles, reduced cortical gray matter
Decreased volume of limbic structures (amygdala, hippocampus)
Reduced frontal lobe volume (explains cognitive symptoms)
Hypofrontality on PET (reduced prefrontal metabolic activity at rest)

4. Neurodevelopmental Model

Insult during fetal brain development (viral infections in 2nd trimester, e.g., influenza)
Prenatal malnutrition, obstetric complications
Abnormal neural migration leading to cortical disorganization (not gliosis - distinguishes it from degenerative diseases)

5. Psychosocial Factors

High expressed emotion (EE) in families - criticism, hostility, over-involvement - increases relapse rates
Life stressors can precipitate episodes
Cannabis use - strong association; high-potency THC increases risk
Urban birth/upbringing, immigration (minority stress)

Symptoms

Symptoms are classically divided into three groups:

A. Positive Symptoms (Abnormal behaviors present)

Associated with acute psychotic episodes; respond to antipsychotics.

Hallucinations:

Auditory (most common) - voices commenting, voices conversing (2 or 3rd person)
Visual, olfactory, somatic/tactile

Delusions:

Persecutory (most common), grandiose, religious, somatic
Delusions of reference, control, guilt/sin, jealousy
Schneider's First Rank Symptoms: Thought insertion, thought withdrawal, thought broadcasting, delusional perception, passivity phenomena, somatic passivity, auditory hallucinations (running commentary, third-person voices)

Bizarre behavior:

Disorganized/bizarre dress and conduct, repetitive or stereotyped behaviors

Disorganized speech/thought:

Loosening of associations, tangentiality, incoherence, neologisms, word salad, clang associations, thought blocking, poverty of content

B. Negative Symptoms (Absence of normal behaviors)

Associated with disease progression; harder to treat; predict poor prognosis.

Affective flattening - reduced emotional expression
Alogia - poverty of speech/thought
Avolition - reduced goal-directed behavior
Anhedonia - inability to experience pleasure
Asociality - social withdrawal
Anergia - lack of energy
Attentional impairment

C. Cognitive Symptoms

Subtle but highly disabling; major determinant of functional outcome.

Impaired working memory
Impaired attention and vigilance
Poor executive functioning (frontal lobe)
Impaired verbal fluency and processing speed

DSM-5 Diagnostic Criteria

A. Two (or more) of the following for ≥1 month (at least one must be 1, 2, or 3):

Delusions
Hallucinations
Disorganized speech
Grossly disorganized or catatonic behavior
Negative symptoms

B. Level of functioning is markedly below premorbid level (work, self-care, interpersonal)

C. Continuous signs for at least 6 months (including prodromal/residual phases)

D. Schizoaffective disorder and mood disorder with psychotic features excluded

E. Not due to substances or medical condition

F. If autism spectrum disorder/childhood communication disorder present, schizophrenia diagnosed only if prominent delusions/hallucinations for ≥1 month

ICD-10 Subtypes (Clinically Important)

Subtype	Key Features
Paranoid	Predominantly delusions (persecutory/grandiose) ± auditory hallucinations; relatively preserved affect and volition; best prognosis
Hebephrenic (Disorganized)	Prominent negative affect, inappropriate/flat mood, disorganized behavior, social isolation; onset <25 yrs; worst prognosis
Catatonic	Marked psychomotor disturbance - stupor, rigidity, waxy flexibility, negativism, posturing, agitation; has become rare
Undifferentiated	Meets criteria but doesn't fit any subtype
Residual	Chronic phase - mainly negative symptoms; hallucinations/delusions absent or mild; ~30% of cases
Simple	Gradual onset of negative symptoms without clear positive psychotic phase

Course and Prognosis

Premorbid phase → Prodromal phase (months to years) → Active psychotic phase → Residual phase

Classic course: exacerbations and remissions; each relapse may worsen baseline
Positive symptoms tend to become less severe with age
Negative/cognitive symptoms can increase over time
20% show no active symptoms by age 65

Good Prognostic Factors ("GOPAL")

Good premorbid functioning
Onset late/acute
Precipitating factors identifiable
Affective symptoms present
Less negative symptoms; female sex; married; good social support; no family history

Poor Prognostic Factors

Early insidious onset; male sex; unmarried; family history; negative symptoms dominant; poor insight; prior hospitalizations; low socioeconomic status

Rule of thirds:

~1/3 recover significantly
~1/3 show moderate improvement with some disability
~1/3 remain severely impaired

Investigations/Assessment

Rating Scales:

PANSS (Positive and Negative Syndrome Scale) - gold standard for symptom severity
BPRS (Brief Psychiatric Rating Scale)
SAS (Simpson-Angus Scale) - extrapyramidal side effects
AIMS (Abnormal Involuntary Movement Scale) - tardive dyskinesia
BARS (Barnes Akathisia Rating Scale)

Neuropsychological testing: Halstead-Reitan battery, Luria-Nebraska battery - show bilateral frontotemporal dysfunction

Brain Imaging: Enlarged ventricles, cortical atrophy; hypofrontality on PET/fMRI

Treatment

1. Antipsychotic Medications

First Generation (Typical/Conventional) Antipsychotics - primarily D2 blockade

High potency: Haloperidol, trifluoperazine, fluphenazine
Low potency: Chlorpromazine, thioridazine
Highly effective for positive symptoms
Significant extrapyramidal side effects (EPS): parkinsonism, akathisia, tardive dyskinesia
Neuroleptic malignant syndrome (NMS) - rare but life-threatening

Second Generation (Atypical) Antipsychotics - D2 + 5-HT2A blockade

Clozapine (gold standard for treatment-resistant schizophrenia) - risk of agranulocytosis (1-2%), requires WBC monitoring
Risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, amisulpride
Better for negative symptoms; less EPS; more metabolic side effects (weight gain, diabetes, dyslipidemia)

Treatment-Resistant Schizophrenia:

Defined as failure of ≥2 adequate antipsychotic trials (4-6 weeks each at adequate doses)
Clozapine is first-line for treatment-resistant cases
Adjunctive options: lamotrigine, mirtazapine, memantine

Long-acting Injectable (LAI/depot) antipsychotics - for poor compliance (e.g., fluphenazine decanoate, haloperidol decanoate, risperidone LAI)

2. Electroconvulsive Therapy (ECT)

Useful in acute and catatonic schizophrenia
About as effective as antipsychotics in recent-onset cases
Can supplement antipsychotics in poorly responding patients

3. Neuromodulation

TMS (Transcranial magnetic stimulation) and tDCS - early evidence for hallucinations and negative symptoms

4. Psychosocial Therapy (Essential component)

Therapy	Purpose
Social Skills Training	Improve interpersonal communication, self-sufficiency
Cognitive Behavioral Therapy (CBT)	Address residual symptoms, coping strategies
Family Therapy	Reduce expressed emotion (EE), psychoeducation
Cognitive Remediation	Target cognitive deficits
Vocational Rehabilitation	Supported employment, independent living
Assertive Community Treatment (ACT)	Intensive community-based care

Differential Diagnosis

Always rule out:

Organic causes: Brain tumors, temporal lobe epilepsy, CNS infections (encephalitis), Wilson's disease, Huntington's disease, SLE
Substance-induced psychosis: Cannabis, cocaine, amphetamines, PCP, LSD, steroids
Schizoaffective disorder: Prominent mood symptoms meeting criteria for major depressive/manic episode concurrent with psychosis
Mood disorder with psychotic features (psychosis only during mood episodes)
Brief psychotic disorder (<1 month), Schizophreniform disorder (1-6 months)
Delusional disorder (non-bizarre delusions, no other psychotic symptoms)
Personality disorders: Schizotypal, schizoid, paranoid PD

Schneider's First Rank Symptoms (Clinically Examinable)

These are pathognomonic of schizophrenia (when organic cause excluded):

Auditory hallucinations: thought echo (gedankenlautwerden), running commentary, third-person voices discussing patient
Thought insertion
Thought withdrawal
Thought broadcasting
Delusional perception (2-stage: normal perception → delusional meaning)
Somatic passivity
Made feelings, impulses, and acts (passivity phenomena)

Key Points for Exams

Dopamine hypothesis: mesolimbic excess = positive symptoms; mesocortical deficit = negative symptoms
Antipsychotics are effective primarily through D2 receptor blockade
Clozapine = treatment-resistant schizophrenia; main risk = agranulocytosis (monitor CBC weekly for first 6 months, then fortnightly)
Tardive dyskinesia = late-onset, irreversible involuntary movements from prolonged D2 blockade; most common in elderly females
Neuroleptic Malignant Syndrome (NMS) = hyperthermia + rigidity + autonomic instability + altered consciousness - stop antipsychotic, treat with dantrolene/bromocriptine
MZ twin concordance 50% (not 100%) proves environmental factors also required
Enlarged ventricles on CT/MRI = most consistent structural finding
Schizophrenia has NO pathognomonic laboratory or imaging test - diagnosis is clinical

Source: Kaplan & Sadock's Synopsis of Psychiatry, 12th Edition; Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 11th Edition

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