Schizophrenia

Schizophrenia is a general term for a group of psychotic illnesses (disorders in which a person loses contact with reality) that are characterized by disturbances in thinking, emotional reaction, and behaviour. Schizophrenia is a disabling illness with a prolonged course that almost always results in chronic ill health and some degree of personality change.

Onset can be at any age but is most common in late adolescence and the early 20s. No causes have been identified, but many have been implicated. It is likely that inheritance plays a role. Disruption of the activity of some neurotransmitters (chemicals that transmit signals between nerve cells) in the brain is a possible mechanism. Brain imaging has revealed abnormalities of structure and function in affected people.

Symptoms and signs

Schizophrenia may begin insidiously, with the person becoming slowly more withdrawn and losing motivation. In other cases, it comes on suddenly, often in response to external stress. The main signs are delusions (fixed, irrational ideas) such as those of persecution (which are typical of paranoid schizophrenia); hallucinations (perceptions that occur without any external stimulus), and thought disorder.

Hallucinations are usually auditory (in which the person hears voices talking about him or her), but may also be visual or tactile. Thought disorder leads to impaired concentration and thought processes; it is often reflected in muddled and disjointed speech and bizarre responses to questions. The person may believe that his or her thoughts are being controlled by outside forces or broadcast to others.

As the illness progresses, the person’s emotions become blunted; he or she also becomes detached from others and loses interest in usual occupations. Behaviour is eccentric, and self-neglect common. In a rare form of schizophrenia, catatonia may occur. In this condition, rigid postures are adopted for prolonged periods, or there are outbursts of repeated movement.

Diagnosis and treatment

Diagnosis may take some time, and in some cases, it may be difficult to make a diagnosis at all. Treatment is mainly with antipsychotic drugs, such as phenothiazine drugs, and the new atypical antipsychotic drugs such as risperidone. In some cases, the drugs are usually given as monthly depot injections. Once the symptoms are controlled, community care, vocational opportunities, and family counselling can help to prevent a relapse. Some people may make a complete recovery; however, most sufferers have relapses punctuated with partial or full recovery. A small proportion have a severe life-long disability

Articles about schizophrenia - technical:

Schizophrenia - technical article

Essentials

Schizophrenia—is characterized by phenomena that qualitatively differ from everyday experience. These may be ‘positive symptoms’, commonly auditory hallucinations and/or bizarre delusions, or ‘negative symptoms’, commonly including a loss of emotion (flat affect), apathy, self-neglect, and social withdrawal. Acute positive symptoms generally respond well to any antipsychotic drug, but prognosis is often poor, with most suffering chronic symptoms, numerous relapses, unemployment, and social isolation.

Introduction

Schizophrenia is characterized by phenomena that qualitatively differ from everyday experience: delusions, hallucinations, disorganized speech/behaviour, and negative symptoms. Onset is in early adulthood (median age 25 years). Men tend to get the illness earlier, more severely, and possibly more often than women. The incidence is only 15 in 100 000 of the population per year, but the prevalence is about 5 in 1000 due to chronicity, and the lifetime risk is 1%.

Aetiology

Recent research, using reliable diagnostic criteria based on clinical features since diagnostic laboratory tests are not available, has established that schizophrenia is multifactorial, with polygenic, neurobiological, and psychosocial components.

Genetic factors account for 80% of the liability to schizophrenia: having an affected relative increases the risk 5 to 50 times, depending on the relationship. Several plausible genes, such as neuregulin 1, have been identified in recent years. Other risk factors include obstetric complications, developmental problems, and cannabis use, but these only double the risk. Stressful life events can be precipitants, but only in those otherwise predisposed.

There are subtle abnormalities of brain structure and function (particularly of the temporal and frontal lobes) in both chronic and first episode cases. Developmental abnormalities in brain structure (e.g. hippocampal volume) and function (e.g. dopamine sensitivity), probably exacerbated by drug and/or stress related changes around onset, are thought to disrupt frontotemporal integration and bring on symptoms, but direct evidence is limited.

Clinical features

Hallucinations and delusions are ‘positive symptoms’, meaning that they are abnormal by their presence. Hallucinations are perceptions in the absence of stimuli. They are usually auditory voices speaking the patients’ thoughts or commenting on their actions. Hallucinations in other senses can occur but suggest a neurological disorder. Delusions are unshakeable false beliefs. Persecutory (‘paranoid’) delusions are common but occur in all psychoses. Delusions of passivity (actions or feelings ‘made’ by external forces) and other bizarre beliefs are more specific. The other positive symptom is thought disorder—an illogical sequence of thoughts (as revealed in speech).

‘Negative symptoms’ are features that are abnormal by their absence: these commonly include a loss of emotion (flat affect), apathy, self-neglect, and social withdrawal. These may be prodromal, but are more common in chronic patients.

Differential diagnosis

Prodromal symptoms can be similar to depression. Drug intoxication can cause positive symptoms, but also disorientation. Neurological causes, e.g. temporal lobe epilepsy or brain tumours, are rare. Delusions of passivity can be confused with obsessional ideas, but the latter are recognized as one’s own. Negative symptoms can be confused with depression or parkinsonism. The distinction of schizophrenia from bipolar disorder is based on whether psychotic or affective features predominate; occasionally, if both are notably present, a diagnosis of schizoaffective disorder is appropriate.

Management

Acute positive symptoms generally respond well to any antipsychotic drug (Table 1). These work by dopamine receptor blockade. The main adverse effects are sedation, weight gain, and extrapyramidal syndromes (acute dystonia, akathisia, parkinsonism, tardive dyskinesia), which are best avoided by minimizing dosage, but dystonias and parkinsonism respond to anticholinergics. Medication should be continued for at least 2 years after an acute episode to reduce relapse
rates.

Patients often refuse medication, due to adverse effects or lack of insight. Some are suitable for depot medication (intramuscular injections of esterified antipsychotics, see Table 1. The second generation antipsychotics generally cause fewer extrapyramidal problems but more weight gain. It is claimed that they are effective in those with negative and treatment-resistant positive symptoms, but clozapine is the only proven such treatment. Clozapine is the definitive and arguably only ‘atypical’ antipsychotic, but carries a considerable risk of neutropenia and agranulocytosis. These treatments are not contraindicated in pregnancy, as they confer only a small increased risk of teratogenicity and an untreated psychosis is often more dangerous.

There are few effective nondrug treatments. Illness education reduces relapse rates, as does teaching social skills, but these may primarily work by improving drug compliance. Early enthusiasm for cognitive therapy, as a means to reduce symptoms and relapse rates, is waning. Vocational rehabilitation helps to get people back to work.

Table 1 Commonly used antipsychotic drugs
Type/name of drug Optimal dosea Main side effects
Phenothiazines
  • Chlorpromazine
  • Thioridazine
  • Trifluoperazine
  • 400–600 mg/day
  • 400–600 mg/day
  • 20–30 mg/day
  • Sedation
  • Anticholinergic
  • Extrapyramidal
Butyrophenones
Haloperidol 8–12 mg/day Extrapyramidal
Benzamides
  • Sulpiride
  • Pimozide
  • 800–1200 mg/day
  • 8–10 mg/day
  • Minimal
  • Minimal
Depot injections
  • Flupentixol decanoate
  • Fluphenazine decanoate
  • Haloperidol decanoate
  • 40 mg every 2 weeks
  • 25 mg every 2 weeks
  • 100 mg monthly
  • Extrapyramidal
  • Extrapyramidal
  • Extrapyramidal
Second-generation drugs
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Amisulpiride
  • 6 mg/day
  • 15 mg/day
  • 300–600 mg/day
  • 800–1200 mg/day
  • Extrapyramidal
  • Weight gain
  • Sedation
  • Agitation
Atypicals
Clozapine 300–600 mg/day Hypersalivation

a This dose of chlorpromazine is established from meta-analyses. Others are calculated as chlorpromazine equivalents, but these are uncertain for depot, second generation, and atypical drugs.

Primary prevention is not a realistic prospect until better understanding of the pathogenesis of schizophrenia allows early detection. There is some evidence that earlier treatments may be associated with a slightly better prognosis, but the trials are small and rarely blind.

Prognosis

The prognosis is generally poor. About 25% of patients will only have one or two episodes, but most will suffer chronic symptoms, numerous relapses, unemployment, and social isolation. Most patients smoke heavily, and many abuse alcohol/drugs, resulting in a high premature mortality rate—especially from myocardial infarction. Suicide is all too common, leading to 5 to 10% of deaths.