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Schizophrenia

NICE Clinical guideline [CG178] Psychosis and schizophrenia in adults: prevention and management. Last updated: Mar 2014. Last reviewed: Jul 2025.

Schizophrenia

General Psychiatry Article Disclaimer

  • DSM-5 criteria or ICD-11 diagnostic requirements are used to structure the Clinical Features and Diagnosis section. The classification system used is selected according to its clarity and suitability for non-specialist learning.
  • The criteria are summarised and simplified rather than reproduced in full, while preserving their original diagnostic meaning.
  • Where appropriate, a student-friendly pattern-recognition summary is provided to highlight the most clinically and exam-relevant features.

Exam tip (re-psychiatry questions)

  • Do not attempt to memorise every DSM-5 or ICD-11 criterion word-for-word. However, it is important to read through the criteria and become familiar with the key symptom clusters, duration thresholds, exclusions, and distinguishing features highlighted in this article.
  • Exam questions may not provide every feature required to meet the full diagnostic criteria. Familiarity with the criteria can help one recognise the most likely diagnosis, exclude important alternatives, and narrow the differential diagnosis.

Causes and Risk Factors

The exact cause of schizophrenia is unknown [Ref]

Category Description / risk factors
Genetic predisposition Schizophrenia is highly heritable (~81% heritability)
  • Risk is significantly higher in monozygotic twins than in distant relatives
  • Complex polygenic contribution
Prenatal and perinatal exposure
  • Advanced paternal age at conception
  • Pregnancy and obstetric complications
    • Pre-eclampsia
    • Low birthweight
    • Asphyxia
    • In utero infections (e.g. Toxoplasma gondii, influenza)
  • Born in winter (compared to being born in summer)
Environmental factors
  • Early-life trauma and abuse (e.g. neglect, physical abuse, sexual abuse)
  • Cannabis use (regular, daily use)
  • Migrants
  • Born and raised in an urban setting
  • Psychosocial stress

Pathophysiology

Simplified pathophysiology: [Ref]

  • Dopamine excess in the dorsal striatum → +ve symptoms in schizophrenia
  • Glutamate and GABA deficit in the prefrontal cortex and hippocampus → -ve symptoms in schizophrenia

Clinical Features and Diagnosis

High-yield pattern recognition for schizophrenia:

  • Active phase symptoms
    • Positive symptoms – psychosis (e.g. delusions, hallucinations, disorganised speech, abnormal behaviour)
    • Negative symptoms (often appear before the onset of positive symptoms), “5As” grouped under 2 groups [Ref]
      • Diminished emotional expression
        • Affect blunted – reduced emotional expression, characterised by reduced facial expressions, poor eye contact, monotonous speech, reduced use of gestures
        • Alogia – poverty of speech characterised by a reduction in the quantity or spontaneous content of speech
      • Avolition
        • Avolition – reduced initiation, self-motivation, and persistence in goal-directed, purposeful activities (e.g. poor grooming/hygiene, withdrawing from work or school)
        • Asociality – reduced social interactions and initiative, due to reduced interest in forming relationships with others
        • Anhedonia – inability to experience pleasure (NB patients with schizophrenia retain the ability to experience consummatory pleasure but have a profound deficit in anticipatory pleasure, reducing drive in pursuing goal-directed behaviour)
  • Functional impairment
  • Duration: ≥6 months with at least 1 month of active-phase symptoms

DSM-5 criteria for schizophrenia, ALL must be met: [Ref]

Diagnostic criteria Description
Characteristic symptoms (“active-phase symptoms”) At least 2 of the following, and at least 1 from points 1-3:
  1. Delusions
  2. Hallucinations
  3. Disorganised speech
  4. Grossly disorganised or catatonic behaviour
  5. Negative symptoms (i.e. diminished emotional expression, or avolition)
Functional impairment For a significant portion of the time since the onset of the disturbance, level of functioning in one or more major areas, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset

Or when the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning

Duration Continuous signs of disturbance for at least 6 months

Within the 6-month period, there must be at least 1 month of active-phase symptoms (i.e. meeting the row 1 criteria)

Exclusion The following have been excluded:
  • Schizoaffective disorder – as no major depressive or manic episodes have occurred concurrently with the active-phase symptoms
  • Depressive or bipolar disorder with psychotic features – as mood episodes that occurred during active-phase symptoms have been present for a minority of the total duration

The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition

Relationship to autism or communication disorder If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month

Complications

[Ref]

Category Description
Mortality and suicide
  • Reduced life expectancy (~15.2 years)
  • 12x higher risk of suicide
Psychiatric comorbidities Schizophrenia has a strong bidirectional relationship with other mental health conditions

Increased risk of developing:

  • Depression
  • Eating disorder
  • Personality disorders
Medical comorbidities Increased risk of:
  • Cardiovascular diseases
  • Respiratory diseases
  • Malignancy

Primarily caused by poor lifestyle factors (e.g. smoking, poor diet, sedentary lifestyle) and antipsychotic-related adverse effects

Differential Diagnosis: Schizophrenia Spectrum and Related Disorders

Primary psychotic disorders: [Ref]

Disorder High-yield distinguishing features
Schizophrenia
  • At least 2 of the following active-phase symptoms:
    • Delusions
    • Hallucinations
    • Disorganised speech
    • Grossly disorganised or catatonic behaviour
    • Negative symptoms (i.e. diminished emotional expression, or avolition)
  • Duration: ≥6 months, including ≥1 month of active symptoms
  • Associated with marked functional impairment
Schizophreniform disorder
  • Same schizophrenia active-phase symptoms criteria
  • Duration: 1-6 months
  • Marked functional impairment is NOT required
Schizoaffective disorder
  • Schizophrenia active-phase symptoms PLUS a major mood episode (depressive OR manic episode)
  • Mood episodes are present most of the time during the illness duration
  • ≥2 weeks of delusions or hallucinations with NO major mood episode
Brief psychotic disorder
  • Sudden onset of psychosis (delusions, hallucinations, disorganised speech and/or grossly disorganised or catatonic behaviour)
  • Duration: 1 day – 1 month
  • Followed by a full return to previous level of functioning
Delusional disorder
  • ≥1 Delusion
  • Duration: ≥1 month
  • No prominent additional psychotic features (specifically, the schizophrenia active-phase symptoms criteria are NOT met)

Important mimics / differentials: [Ref1][Ref2]

Disorder High-yield distinguishing features
Substance / medication-induced psychotic disorder (drug-induced psychosis)
  • Presence of delusion and/or hallucination
  • Clear temporal relationship: symptoms develop during or within 1 month of substance intoxication or withdrawal
  • Common substances
    • Cannabis
    • Stimulants (esp. cocaine and amphetamines)
    • Hallucinogens (e.g. LSD)
    • Alcohol withdrawal
  • Common medications
    • Mainly levodopa and dopamine agonists
    • Systemic corticosteroids
Psychotic disorder due to another medical condition (secondary / organic psychosis) New psychosis (esp. prominent visual hallucinations) + neurological / systemic abnormalities or atypical presentation → consider secondary / organic psychosis

Key causes:

  • Lewy body dementia
  • Brain tumour or other structural brain lesions
  • Autoimmune encephalitis (esp. anti-NMDA receptor encephalitis)
  • Wilson disease
Mania with psychotic features (bipolar disorder)
  • Psychotic symptoms plus prominent manic syndrome (e.g. elevated / irritable mood, increased activity / energy, reduced need for sleep, pressured speech)
  • Psychosis occurs in the context of the mood episode (unlike schizoaffective disorder where psychosis also occurs independently of a major mood episode)
Schizotypal personality disorder
  • Longstanding pattern beginning by early adulthood
  • Eccentric idea / behaviour + magical thinking / ideas of reference + interpersonal difficulties
  • No obvious psychotic episodes
Schizoid personality disorder
  • Longstanding pattern beginning by early adulthood
  • Not interested in others, resulting in social isolation + no or few friends + not interested in relationships
  • No odd beliefs, perceptual distortions or psychosis

Management

Preventing Psychosis (At Risk Patients)

Indication Individuals who are distressed + have a decline in social functioning + any of the following
  • Transient or attenuated psychotic symptoms
  • Other experiences or behaviours suggestive of possible psychosis
  • 1st degree relative with history of psychosis or schizophrenia
Prevention approach Refer to specialist mental health service
  • Primary intervention: individual CBT +/- family intervention
  • If symptoms, distress, or impaired functioning persist after psychological treatment but a clear diagnosis of psychosis cannot be established → monitor regularly for up to 3 years

Do NOT offer antipsychotics to prevent the development of psychosis

Managing First Episode Psychosis

First episode psychosis must be assessed by and managed in secondary care. Antipsychotics should not be started in primary care.

Core treatment:

  • Psychological interventions (both individual CBT and family intervention), PLUS
  • Oral antipsychotic monotherapy

Consider group art therapy to help manage negative symptoms and promote recovery

Further information on antipsychotic choice:

1st line choice of antipsychotic NICE did NOT recommend a single preferred 1st line antipsychotic
  • Choice of antipsychotic should be guided by the side-effect profile and which side effect the patient is most willing to tolerate (including metabolic, extrapyramidal, cardiovascular and prolactin-related effects)
  • Clozapine is reserved for treatment-resistant schizophrenia and is not a routine 1st line antipsychotic (see below for indications)
Escalating antipsychotic treatment Before escalating antipsychotic therapy, always:
  • Establish adherence
  • Optimise dosing and duration
  • Standard therapeutic trial: 4-6 weeks at optimum dosage

Escalation pathway:

  • First escalation: switch to an alternative antipsychotic
  • Further escalation: offer clozapine if the patient did not respond adequately to at least 2 different antipsychotics (at least 1 must be a 2nd generation antipsychotic)
  • If the patient did not respond to clozapine: consider adding another antipsychotic to clozapine

Antipsychotic depots are long-acting injectables (usually IM injections) that can be considered if:

  • Patient prefers the method of administration, or
  • To avoid non-adherence

See the Antipsychotic Pharmacology for more information on antipsychotics (including 1st generation vs 2nd generation, side effects, monitoring)

References

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