• A chronic psychotic disorder characterized by delusions, hallucinations, disorganization, negative symptoms, and cognitive deficits:
    • Premorbid phase:
      • Development of negative symptoms: Apathy, anhedonia, avolition, alogia, affect blunting
      • Deterioration of personal, social, and cognitive functioning
    • Active phase:
      • Development of positive symptoms: Paranoia, ideas of reference, delusions, hallucinations, disorganized speech, disorganized behavior
      • May be precipitated by a stressful event or substance use
    • Residual phase:
      • Patients are left with negative symptoms, impaired social and cognitive abilities
      • Psychotic symptoms may persist
  • Onset typically early in adulthood
    • Men: Ages 18–25; Women: Ages 25–35
    • Rarely occurs in childhood or age >45
  • Common comorbidities: Depression, anxiety, substance abuse, neurological symptoms, metabolic disturbances
  • Life expectancy on average is 28.5 yr lower than the general population:
    • Cardiovascular disease is the most common cause of death
    • 5% of patients commit suicide
    • Patients may have difficulty accessing or adhering to medical treatment
    • Disorganized thinking, abnormal behavior, and delusions may obscure the detection of medical illness when patients present for care
  • Medication nonadherence is a common reason for psychiatric decompensation and presentation to the ED


  • Pathophysiology unclear but dopamine and glutamate pathways are implicated
  • Genetic component (concordance rate of 50% in monozygotic twins)
    • Likely polygenetic disorder: Impact of multiple genes with small, additive effect
    • Complement component C4: Increased expression associated with increased synaptic pruning during neurodevelopment
    • Higher risk in patients with DiGeorge syndrome (22q11.2 deletion)
  • Perinatal risk factors:
    • Influenza during second trimester
    • Maternal and postnatal infections
    • Advanced paternal age
  • Environmental risk factors:
    • Immigration
    • Urban living environment
  • Use of cannabis may unmask psychosis in predisposed individuals

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