About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Positive symptoms: delusions (persecutory, referential, control), auditory hallucinations (third-person, running commentary), thought disorder
- Negative symptoms: avolition, flat affect, alogia, anhedonia, social withdrawal — harder to treat, major cause of disability
- Schneider first-rank symptoms: auditory hallucinations (third-person/running commentary), thought insertion/withdrawal/broadcasting, delusions of control, passivity phenomena
- First-line: oral atypical antipsychotic (risperidone, olanzapine, aripiprazole, quetiapine) — choice made jointly with patient
- Treatment-resistant schizophrenia (failed ≥2 antipsychotics): clozapine — the ONLY drug with proven efficacy in this group
- Clozapine requires mandatory blood monitoring for agranulocytosis (weekly for 18 weeks, then fortnightly, then monthly)
Overview
Schizophrenia is a chronic psychotic disorder characterised by distortions in thinking, perception, emotions, language, sense of self, and behaviour. Symptoms are categorised as positive (delusions, hallucinations, disorganised speech and behaviour — reflecting an excess of normal function), negative (avolition, flat affect, alogia, anhedonia, social withdrawal — reflecting a loss of normal function), and cognitive (impaired attention, working memory, and executive function). The dopamine hypothesis proposes that psychotic symptoms result from excess dopaminergic activity in the mesolimbic pathway, while negative symptoms arise from reduced dopamine in the mesocortical pathway. Glutamate, serotonin, and GABA systems are also implicated.
Epidemiology
Schizophrenia has a lifetime prevalence of approximately 0.7–1%. Incidence peaks in late adolescence/early adulthood: 18–25 in males, 25–35 in females. Males have an earlier onset and often a more severe course. Risk factors include family history (10× risk in first-degree relatives), urban upbringing, migration, childhood adversity, cannabis use (particularly high-potency, adolescent-onset), and obstetric complications. The condition is associated with a reduced life expectancy of 15–20 years, largely due to cardiovascular disease, metabolic syndrome, and suicide (~5% lifetime risk).
Clinical Features
Symptoms
Auditory hallucinations — third-person voices discussing the patient, running commentary on actions, command hallucinations
Delusions — persecutory (being followed, monitored), referential (special messages), grandiose, bizarre
Delusions of control/passivity: thought insertion, thought withdrawal, thought broadcasting, made feelings/actions
Disorganised speech: loosening of associations, tangentiality, word salad, neologisms
Negative symptoms: avolition (lack of motivation), flat affect, alogia (poverty of speech), anhedonia, social withdrawal
Cognitive impairment: poor concentration, impaired working memory, executive dysfunction
Catatonia: immobility, mutism, posturing, waxy flexibility, stupor — psychiatric emergency
Suicidal ideation — lifetime suicide risk ~5%
Signs
Flat or incongruent affect, poor rapport, guarded behaviour
Responding to unseen stimuli (whispering, looking around, covering ears)
Disorganised behaviour, poor self-care, social withdrawal
Formal thought disorder on MSE: tangential, circumstantial, loosened associations
Poor insight — may deny illness or need for treatment
Investigations
First-line
Clinical assessment (MSE)Comprehensive psychiatric history and mental state examination. Assess positive symptoms, negative symptoms, insight, risk, and functioning
Collateral historyFrom family/friends — essential as patient may lack insight. Assess duration, prodromal symptoms, functional decline
Risk assessmentSuicide (5% lifetime risk), self-neglect, risk to others (rare but assess), vulnerability, safeguarding
Second-line
BloodsFBC, U&Es, LFTs, TFTs, glucose, HbA1c, lipid profile, calcium, B12/folate — exclude organic causes and baseline metabolic monitoring
Urine drug screenExclude substance-induced psychosis (cannabis, amphetamines, cocaine, novel psychoactive substances)
CT/MRI headTo exclude organic pathology — space-occupying lesion, encephalitis, demyelination. Recommended in first-episode psychosis
Specialist
Neuropsychological testingAssess cognitive impairment — useful for rehabilitation planning and differentiating from organic dementias
EEGIf temporal lobe epilepsy or autoimmune encephalitis suspected
1
First-episode psychosis — Early Intervention in Psychosis (EIP) team
- Refer urgently to Early Intervention in Psychosis service
- Oral antipsychotic: choose JOINTLY with the patient. Options include risperidone, olanzapine, aripiprazole, quetiapine, amisulpride
- Start low, titrate slowly. Trial for 4–6 weeks at adequate dose before considering switch
- CBT for psychosis (CBTp): offered to all patients alongside medication
- Family intervention: offered to all families/carers — reduces relapse by ~50%
2
Second antipsychotic trial
- If inadequate response to first antipsychotic at adequate dose for adequate duration → switch to a DIFFERENT antipsychotic
- Ensure adherence before switching — consider depot (long-acting injectable) if adherence is an issue
- At least one of the two trials should be with an antipsychotic other than clozapine
3
Treatment-resistant schizophrenia → clozapine
- Clozapine after failure of ≥2 antipsychotics (at least one should be a non-clozapine atypical)
- Clozapine is the ONLY antipsychotic with proven superiority in treatment-resistant schizophrenia
- Requires mandatory blood monitoring: FBC weekly for 18 weeks → fortnightly for 1 year → monthly thereafter
- Risk: agranulocytosis (1–2%), metabolic syndrome, sedation, hypersalivation, constipation (can be severe), myocarditis, seizures
- Registered with Clozapine Patient Monitoring Service (CPMS)
4
Psychosocial interventions
- CBTp for all patients (NICE mandated) — reduces positive symptoms and distress
- Family intervention: 10+ sessions over 3–12 months
- Supported employment, education, and social skills training
- Physical health monitoring: weight, BMI, glucose, lipids, BP — at baseline, 3 months, then annually (metabolic screening)
Complications
- Suicide: ~5% lifetime risk, highest in young males early in the illness
- Metabolic syndrome: Weight gain, T2DM, dyslipidaemia — antipsychotic-related (especially olanzapine, clozapine)
- Cardiovascular disease: Leading cause of excess mortality — 15–20 years reduced life expectancy
- Clozapine-specific: Agranulocytosis (1–2%), myocarditis, severe constipation/ileus, metabolic syndrome
- Extrapyramidal side effects: Parkinsonism, akathisia, acute dystonia, tardive dyskinesia — more common with typicals (haloperidol)
- Neuroleptic malignant syndrome: Rare but life-threatening — fever, rigidity, autonomic instability, raised CK
UKMLA Exam Tips
- 1Schneider first-rank symptoms: third-person hallucinations, running commentary, thought insertion/withdrawal/broadcasting, passivity/made phenomena
- 2First-line antipsychotic: ATYPICAL (risperidone, olanzapine, aripiprazole). Choice is shared decision with patient
- 3Treatment-resistant schizophrenia (failed ≥2 antipsychotics) = clozapine. No other antipsychotic has proven superiority
- 4Clozapine monitoring: mandatory FBC for agranulocytosis — weekly × 18 weeks → fortnightly × 1 year → monthly
- 5Metabolic monitoring for ALL antipsychotics: weight, glucose, lipids, BP at baseline, 3 months, then annually
- 6Negative symptoms (avolition, flat affect, alogia) cause more disability than positive symptoms and are harder to treat
- 7Cannabis use (especially high-potency, started in adolescence) is a significant risk factor for schizophrenia — exam favourite
practicetest your knowledge on schizophreniaApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — psychiatry and beyond.
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