Schizophrenia

The most common form of psychosis; it is a lifelong condition

Aetiology

Genetic factors

  • 78% heritability
  • Polygenetic inheritance
  • Identified gene alterations include:
    • Neuregulin - a sigalling protein that mediates cell-cell interactions and plays critial roles in the growth and development of multiple organ systems
    • Dysbindin - essential for adaptive neural plasticity
    • DISC-1 - involved in neurite outgrowth and cortical development through its interaction with other proteins

Environmental risk factors

  • 2nd trimester viral illness
  • Obstetric problems - pre-eclampsia, fetal hypoxia, emergency Caesarian section
  • Childhood viral CNS infection - increases risk by 50%
  • Substance misuse, especially cannabis
    • Risk of psychosis is increased by: amphetamines, cocaine, cannabis, novel psychoactive substances ('legal highs')
    • In individuals predisposed to schizophrenia, drug use may precipitate an episode and worsen the overall prognosis

Pathophysiology

Schizophrenia and the brain

  • Mesolimbic pathway has been implicated
  • Robust finding of enlarged ventricles, shows little progression over time
  • Reduced fronto-temporal volume
  • Reduced activation of prefrontal areas on specific tasks e.g. Stroop test
  • Neurotransmitters:
    • Dopamine has traditionally been implicated (dopamine hypothesis)
    • Serotonin receptors now also thought to be significant
    • There is increasing evidence to show the importance of glutamate receptors

Neurodevelopmental model of SZ

  • Environemental risk factors act in utero
  • Children who later develop SZ have identifiable impaired behaviour, motor and intellectual development from infancy
  • Ventricular enlargement is present at diagnosis and is non-progressive
  • No gliosis
  • BUT stress may act to precipitate onset/relapse

Clinical presentation

'First-rank' symptoms

  • Auditory hallucinations in the third person and/or voices commenting on the person's behaviour
  • Thought abnormalities
    • Thought blocking - sudden cessation of thought
    • Thought withdrawal - refers to a patient’s belief that thoughts can be removed from their mind by others
    • Thought insertion - refers to a patient’s belief that thoughts can be inserted into their mind by others
    • Thought broadcasting - refers to a patient’s belief that others can hear their thoughts
  • Delusional perception - delusions are firm, fixed beliefs based on inadequate grounds, not amenable to a rational argument or evidence to the contrary and not in sync with regional and cultural norms
    • May include persecutory delusions, in which the patient erroneously believes another individual or group is trying to harm them or ideas of reference, in which the individual incorrectly believes specific events relate to them
  • Passivity - people who experience passivity do not feel in control of their actions, thoughts and perceptions, believing them to influenced by an external agent

Other symptoms of acute schizophrenia

  • Behavioural disturbances
  • Other hallucinations
  • Secondary (usually persecutory) delusions
  • Blunting of mood

'Positive' and 'negative' symptom clusters

Schizophrenia is sometimes divided into ‘positive’ and ‘negative’ symptom clusters:
  • Positive schizophrenia is characterized by acute onset, prominent delusions and hallucinations, normal brain structure, a biochemical disorder involving dopaminergic transmission, a good response to neuroleptics, and a better outcome
  • Negative schizophrenia is characterized by a slow, insidious onset, a relative absence of acute symptoms, the presence of apathy, social withdrawal, lack of motivation, underlying brain structure abnormalities and poor antipsychotic response

Subtypes of SZ (20%)

  • Hebephrenic - affective changes are prominent, delusions and hallucinations, feeling and fragmentary, behaviour irresponsible and unpredictable, and mannerisms common
    • The mood is shallow and inappropriate, thought is disorganised, and speech is incoherent
    • There is a tendency to social isolation and negative symptoms
  • Catatonic - movement disorder predominates, alternating between stupor and hyperkinesis
    • Automatic obedience, posuring and waxy flexibility may be seen

Management

Admission to a psychiatric unit is often required at the outset; compulsory admission and possibly enforced treatment under the Mental Health Act may be required
  1. 2nd generation antipsychotic (DA antagonist) e.g. risperidone or olanzapine - titrate up over 6-8 weeks
  1. 1st (e.g. haloperidol) or different 2nd generation antipsychotic - titrate up over 6-8 weeks
  1. Check diagnosis, consider psychological input, optimise social supports, check compliance (consider depot?), consider combining two antipsychotics, consider clozapine