A severe and persistent mental illness characterized by delusions, hallucinations, disorganization of thought and behavior, cognitive dysfunction, and impairment in reality testing


  • Major psychiatric disorder with a variable course, typically involving prodromal, active, and residual psychotic symptoms with disturbances in thought, speech, affect, behavior, and perception
  • DSM-5 eliminated subcategories of schizophrenia (paranoid, disorganized, catatonic, etc.).
  • System(s) affected: central nervous system (CNS)



  • Predominant sex: male-to-female ratio = 1.4:1
  • Age of onset: typically <30 years, earlier in males (late teens to mid-20s) than females (early 20s to early 30s), with a smaller peak that occurs in women >45 years; more subtle changes in cognition and functioning can precede the diagnosis (prodromal period) by several years.

1.1% of the population >18 years old; similar rates in all countries

Etiology and Pathophysiology

  • Stems from a complex interaction between genetic and environmental factors
  • Overstimulation of mesolimbic dopamine D2 receptors, deficient prefrontal dopamine, and aberrant prefrontal glutamate (NMDA) activity results in perceptual disturbances, disordered thought process, and cognitive impairments.

If first-degree biologic relative has schizophrenia, risk is 8–10% (a 10-fold increase). Monozygotic twins have a 48% risk (a 48-fold increase).

Risk Factors

  • Antenatal risk factors include prenatal infection or malnutrition, obstetric complications leading to hypoxia, winter births, postnatal infections requiring hospitalization, urban birth, and advanced paternal age.
  • Risk factors across the lifespan include adolescent cannabis use, childhood trauma, urban residence, autoimmune disorders, severe and repeated stress, lower socioeconomic status, minority status, being a first- or second-generation immigrant, and inadequate social support.

General Prevention

Educate all patients on the risks around cannabis use, especially those in a potential prodromal period or those with a family history of psychosis.

Commonly Associated Conditions

  • Nicotine dependence (>50%) and substance use disorders
  • Metabolic syndrome, diabetes mellitus, obesity, and infectious diseases

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