Schizophrenia

Overview

•Chronic psychotic disorder affecting ~1% of the population; males present earlier (late teens to mid-20s) vs females (late 20s to early 30s)
•Life expectancy reduced by 15-20 years - mainly cardiovascular disease, metabolic complications, and suicide

Pathophysiology

Dopamine pathway dysfunction in schizophrenia
PathwayStateConsequence
MesolimbicOveractivePositive symptoms (hallucinations, delusions)
MesocorticalUnderactiveNegative symptoms, cognitive deficits
NigrostriatalD2 blockade by antipsychoticsExtrapyramidal side effects
TuberoinfundibularD2 blockade by antipsychoticsHyperprolactinaemia

Presentation

•Positive symptoms - hallucinations, delusions, thought disorder, disorganised behaviour
•Negative symptoms - avolition, social withdrawal, flat affect, alogia
•Cognitive deficits - impaired executive function, memory, and attention
•Prodrome - social withdrawal, declining function, odd beliefs before frank psychosis
🎯
Schneider's first-rank symptoms: third-person auditory hallucinations, running commentary, thought insertion/withdrawal/broadcast, delusional perception, passivity phenomena (made actions/feelings/impulses). Historically considered pathognomonic but now understood to be non-specific.
⚠️
Hallucinations in modalities other than auditory (visual, tactile, olfactory) should always prompt consideration of an organic cause.

Investigations

•Baseline bloods - FBC, glucose, lipids, LFTs, renal function, TFTs, prolactin
•Urine drug screen - exclude substance-induced psychosis
•ECG - baseline QTc before antipsychotic initiation (many antipsychotics prolong QTc)
•CT/MRI brain - first episode, atypical features, or neurological signs
•MSE and structured psychiatric assessment - core diagnostic tool

Differential diagnosis

•Substance-induced psychosis - cannabis, amphetamines, cocaine; resolves with abstinence
•Bipolar disorder with psychotic features - psychosis only during mood episodes; prominent mood disturbance
•Schizoaffective disorder - concurrent prominent and persistent mood symptoms alongside schizophrenia-like symptoms
•Brief psychotic disorder - symptoms 1 day to 1 month, often stress-triggered, full return to premorbid function
•Organic causes - anti-NMDAR encephalitis, temporal lobe epilepsy, SOL, thyroid disease, B12 deficiency; always exclude in first-episode psychosis

Diagnostic criteria

ICD-11 vs DSM-5 diagnostic criteria
FeatureICD-11 (UK clinical practice)DSM-5 (research/US)
DurationAt least 1 month6 months continuous (≥1 month active)
Symptoms required≥2 of: delusions, hallucinations, disorganised thinking, passivity/control, negative symptoms, disorganised behaviour, psychomotor disturbance; ≥1 from first four≥2 of: delusions, hallucinations, disorganised speech, disorganised/catatonic behaviour, negative symptoms; ≥1 from first three
🎯
The 6-month requirement in DSM-5 is what differentiates schizophrenia from schizophreniform disorder - this distinction appears in exam vignettes.

Management

🥇 First-line

•atypical (second-generation) antipsychotic - olanzapine, risperidone, quetiapine, aripiprazole - similar efficacy; choice guided by side effect profile and patient factors (avoid olanzapine in obese or diabetic patients)
•CBT for psychosis (CBTp) - NICE recommends offering to all patients; reduces positive symptom severity
•Family intervention - reduces relapse rates by reducing expressed emotion

🥈 Second-line

•switch to different atypical after inadequate trial (≥4-6 weeks at therapeutic dose); or depot long-acting injectable (e.g. paliperidone palmitate, risperidone LAI) where adherence is problematic
•Third-line (treatment-resistant): clozapine - indicated after failure of ≥2 antipsychotics at adequate dose and duration
🚨
Clozapine monitoring: registered with CPMS; FBC weekly for 18 weeks, fortnightly for remainder of year 1, then monthly. Stop immediately if neutrophils <1.5 x10⁹/L (agranulocytosis risk ~1-2%). Also monitor troponin and CRP at baseline and weeks 1-4 for myocarditis.

Complications

•Suicide - lifetime risk ~5-10%; highest in post-discharge period and during depressive episodes
•Tardive dyskinesia - repetitive involuntary orofacial/limb movements from long-term D2 blockade; may be irreversible; assess with AIMS scale
•Neuroleptic malignant syndrome (NMS) - hyperthermia, lead-pipe rigidity, autonomic instability, markedly elevated CK; stop antipsychotic immediately
•Metabolic syndrome - type 2 diabetes, obesity, dyslipidaemia; intrinsic to illness and exacerbated by antipsychotics

Prognosis

•Rule of quarters: ~25% single episode full remission; ~25% significant improvement with some deficit; ~25% partial improvement with ongoing impairment; ~25% treatment-resistant chronic disability

Antipsychotic side effects

Typical vs atypical antipsychotic side effects
Side effectTypical (1st gen)Atypical (2nd gen)
Extrapyramidal effectsHigh - nigrostriatal D2 blockadeLower - 5-HT2A blockade reduces nigrostriatal D2 effect
HyperprolactinaemiaHigh - tuberoinfundibular D2 blockadeLower (variable)
Metabolic syndromeLowerHigh - especially olanzapine, clozapine
SedationVariableCommon - H1 blockade
QTc prolongationSignificant riskVariable