Schizophrenia — Symptoms, Causes & Treatment | MyMedicPlus

Schizophrenia is a severe, chronic psychotic disorder affecting approximately 0.7% of the global adult population — approximately 24 million people worldwide. It is characterised by three symptom domains: positive symptoms (hallucinations, delusions, and disorganised thought), negative symptoms (avolition, flat affect, alogia, and anhedonia), and cognitive impairment (affecting working memory, processing speed, and executive function). Onset typically occurs in late adolescence to early adulthood — the median age of onset is 18-25 in men and 25-35 in women. Schizophrenia has a strong genetic component (heritability approximately 80%) but is clearly multifactorial, with environmental risk factors playing a significant role. It is a leading cause of disability worldwide — ranking in the top 15 causes of years lived with disability (YLDs) globally. Despite the severity of symptoms, approximately 20-25% of people with schizophrenia achieve significant functional recovery with appropriate treatment. Early detection and treatment during the first psychotic episode (duration of untreated psychosis — DUP — less than 3 months) is the most important determinant of long-term functional outcome.

Schizophrenia results from a complex interaction of genetic vulnerability and environmental stressors — the 'two-hit hypothesis.' Neurobiological mechanisms: dopamine dysregulation (hyperactivity in mesolimbic dopamine pathway causing positive symptoms — the basis for antipsychotic efficacy through D2 receptor blockade) and glutamate hypofunction at NMDA receptors in the prefrontal cortex (contributing to negative symptoms and cognitive impairment — the mechanism of ketamine-induced psychosis). Serotonin dysregulation is also implicated. Genetic risk factors: heritability approximately 80%; concordance in identical twins approximately 50% (not 100%, confirming environmental factors); risk is 10% in first-degree relatives, 40-50% if both parents affected. Many common genetic variants with small effects plus rare copy number variants (22q11 deletion — DiGeorge syndrome — confers a 30% lifetime psychosis risk). Environmental risk factors: prenatal exposures (maternal influenza or Toxoplasma gondii infection during second trimester; maternal nutritional deficiency — particularly vitamin D); obstetric complications (hypoxia at birth, caesarean section); cannabis use (especially high-THC products — 2-3x risk in regular users; 5-7x risk with daily use before age 18; may precipitate psychosis in genetically vulnerable individuals); urban birth and upbringing (relative risk 1.7-2.0 — possibly reflecting social fragmentation, pollution, or infection exposure); migration and discrimination (chronic social stress); and childhood trauma (adversity increases risk 3-fold). Structural brain changes (reduced grey matter in prefrontal cortex, enlarged ventricles) are associated features, not diagnostic.

Schizophrenia presents across three symptom dimensions. Positive symptoms (added experiences not normally present): auditory hallucinations (in 60-80% — typically third-person voices commenting on the patient's actions, conversing with each other, or giving commands; voices are perceived as external and real); persecutory delusions (most common — fixed, unshakeable beliefs about being followed, monitored, or conspired against, unrelated to cultural norms); delusions of reference (belief that neutral events — TV programmes, car number plates — carry specific personal messages); thought disorder — disorganised thinking expressed as derailment (knight's move thinking), tangentiality, circumstantiality, or word salad (completely incoherent speech); and catatonic features (psychomotor disturbance — stupor, rigidity, agitation, or waxy flexibility). Negative symptoms (reduction in normal function): avolition (profound reduction in goal-directed behaviour — unable to initiate or sustain purposeful activities); flat affect (reduced facial expression, monotone voice, limited emotional responsiveness); alogia (poverty of speech — brief, empty replies); anhedonia (loss of capacity for pleasure from previously enjoyed activities); and social withdrawal. Negative symptoms are often the most disabling and are poorly responsive to current antipsychotics. Cognitive impairment: impaired working memory, processing speed, verbal fluency, attention, and executive function — present before psychosis onset; a core feature; strongly predicts functional outcomes (work, independent living, relationships). A prodromal phase (months to years before psychosis) features social withdrawal, declining function, mild perceptual disturbances, and subclinical thought disorder.

Schizophrenia is a clinical diagnosis based on DSM-5 or ICD-11 criteria — no single biomarker or imaging test confirms the diagnosis. DSM-5 criteria require at least 2 of the following characteristic symptoms, present for at least 1 month (with at least one being items 1, 2, or 3): (1) delusions; (2) hallucinations; (3) disorganised speech; (4) grossly disorganised or catatonic behaviour; (5) negative symptoms. The disturbance must cause significant functional decline in work, relationships, or self-care for at least 6 months. Organic causes of psychosis must be excluded. Investigations: MRI brain — to exclude structural causes (cerebral tumour, autoimmune encephalitis, vascular lesions); results are typically normal in schizophrenia, though non-specific changes (mild ventricular enlargement, subtle prefrontal grey matter reduction) may be noted as a research finding rather than diagnostic criterion. Blood tests: FBC, metabolic panel, TFTs (thyroid function — hypothyroidism and hyperthyroidism cause psychosis), serum calcium, vitamin B12, folic acid, LFTs. Anti-NMDA receptor antibody panel (serum and CSF): essential to exclude anti-NMDAR encephalitis — which can present identically to first-episode schizophrenia (female predominance, ovarian teratoma, autonomic instability). Urine drug screen: cannabis, amphetamine, cocaine, and phencyclidine (PCP) — substance-induced psychosis must be considered. Formal neuropsychological testing (e.g., MATRICS Consensus Cognitive Battery) quantifies cognitive deficits. The PANSS (Positive and Negative Syndrome Scale) and BPRS (Brief Psychiatric Rating Scale) are standardised rating tools for symptom severity monitoring.

Treatment of schizophrenia is multimodal — combining antipsychotic pharmacotherapy with psychological therapies and psychosocial rehabilitation. Antipsychotic medication: second-generation antipsychotics (SGAs — also called atypical antipsychotics) are first-line: risperidone (2-8 mg/day), olanzapine (10-20 mg/day), quetiapine (400-800 mg/day), aripiprazole (10-30 mg/day), and paliperidone — produce dopamine D2 and serotonin 5-HT2A antagonism. SGAs are preferred over first-generation antipsychotics (FGAs — haloperidol, chlorpromazine) for lower risk of extrapyramidal side effects (EPS — dystonia, akathisia, parkinsonism) and tardive dyskinesia. Clozapine is the most effective antipsychotic and is recommended for treatment-resistant schizophrenia (TRS — defined as failure of at least 2 adequate trials of different antipsychotics at adequate dose for at least 6-8 weeks); 30-60% of TRS patients respond to clozapine; it also reduces suicidality (the only antipsychotic with evidence for suicide reduction) and aggression. However, clozapine requires mandatory haematological monitoring (full blood count weekly for 18 weeks, then fortnightly then monthly) due to the risk of agranulocytosis (occurring in 1-2%). Long-acting injectable (LAI) antipsychotics (e.g., paliperidone palmitate monthly, aripiprazole monohydrate monthly, risperidone microspheres fortnightly) dramatically improve medication adherence compared to oral formulations — relapse rates are 30% lower with LAIs. Psychological therapies: cognitive behavioural therapy for psychosis (CBTp) — NICE-recommended for all patients; reduces positive symptoms, distress, and relapse risk; addresses the meaning and impact of psychotic experiences. Family intervention (psychoeducation) — for patients in close contact with family — reduces relapse rates by 25%. Assertive Community Treatment (ACT): intensive community support for high-risk patients. Supported employment (Individual Placement and Support — IPS): the most effective vocational rehabilitation approach. Social skills training and cognitive remediation therapy address functional deficits.

Tardive dyskinesia (TD): involuntary repetitive movements of the face, tongue, and limbs from long-term D2 receptor blockade — occurs in approximately 5% of patients per year of antipsychotic exposure; partially reversible if detected early and the offending antipsychotic is reduced or switched; VMAT2 inhibitors (valbenazine, deutetrabenazine) provide targeted treatment. Metabolic syndrome: weight gain, insulin resistance, dyslipidaemia, and type 2 diabetes are significantly increased with SGAs — olanzapine and clozapine carry the highest metabolic risk; metabolic monitoring (weight, fasting glucose, and lipids at baseline and every 3-6 months) is essential. Cardiovascular disease: schizophrenia patients have 2-3 times the general population mortality from cardiovascular disease — from metabolic effects of antipsychotics, smoking (70% prevalence in schizophrenia), physical inactivity, and reduced access to healthcare. Suicide: lifetime risk of completed suicide is 5-10% — the highest psychiatric illness suicide risk; depression, command hallucinations, and insight into the illness are major risk factors. Substance use comorbidity affects over 50% of people with schizophrenia — cannabis, alcohol, and stimulants worsen psychosis and increase relapse risk. Social and occupational decline: only 10-20% of schizophrenia patients are employed; social isolation and cognitive impairment are major contributors to functional disability.

Early intervention in psychosis (EIP) services — rapid access to treatment within the first episode of psychosis (within 2 weeks of referral per NICE NG185) significantly reduces long-term disability, hospitalisation rates, and the transition from first-episode psychosis to chronic schizophrenia. The duration of untreated psychosis (DUP) is one of the strongest predictors of outcome — every month of untreated psychosis worsens prognosis. Cannabis avoidance is critical — even for established patients, cannabis use doubles the risk of relapse. Medication adherence is the most important factor preventing relapse — stopping antipsychotics is associated with relapse in 70-80% within 2 years. LAI antipsychotics improve adherence by approximately 30% compared to oral formulations. Regular metabolic monitoring: weight, BMI, waist circumference, fasting blood glucose, and lipid profile at baseline and every 3 months — essential given the cardiovascular and metabolic risks of antipsychotics. Clozapine monitoring: mandatory full blood count weekly for 18 weeks then monthly — patients must be registered with the Clozapine Patient Monitoring Service (CPMS). Psychosocial rehabilitation: individual placement and support (IPS) employment programmes, family psychoeducation, and peer support groups improve functional outcomes. Healthy lifestyle support: smoking cessation programmes (adapted for psychiatric patients), exercise prescriptions, and dietary advice address the elevated cardiometabolic risk.

Call emergency services or take the person to A&E immediately if: they are expressing ideas of harming themselves or others; behaving in a way that puts themselves or others at risk; or showing sudden severe agitation, confusion, or threatening behaviour — urgent psychiatric assessment and possible compulsory admission under the Mental Health Act may be required. Seek urgent GP assessment within 24–48 hours if someone close to you is showing early signs of a first psychotic episode: social withdrawal and functional decline over several weeks; talking or laughing to themselves; expressing beliefs that seem bizarre or fixed (e.g., being watched, receiving special messages, being controlled); hearing voices that others cannot hear. Early intervention in psychosis (EIP) services significantly improve long-term outcomes — the duration of untreated psychosis (DUP) is one of the strongest predictors of outcome. For established patients: contact the community mental health team or crisis line immediately if: they stop their antipsychotic medication suddenly (high relapse risk within weeks); they develop signs of clozapine-related agranulocytosis (fever, sore throat, mouth ulcers — do not wait, go to A&E with their clozapine card); or family members feel unable to safely manage a deteriorating mental state at home — crisis resolution and home treatment teams can prevent unnecessary hospital admission.