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

Aetiology

Genetic factors

• 78% heritability
• Polygenetic inheritance
• Identified gene alterations include:
  • Neuregulin - a signalling protein that mediates cell-cell interactions and plays critical 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

• Environmental risk factors act in utero