Etiology and Pathophysiology of Schizophrenia

1. Overview & Epidemiology

• Definition: Schizophrenia is a chronic psychotic disorder of complex, multifactorial etiology — genetic vulnerability interacting with environmental and neurodevelopmental insults. No single cause is proven (the explicit point of PSY-4.50).
• Lifetime prevalence: ~1% worldwide (1 in 100); broadly uniform across cultures.
• Sex: Affects males and females equally, but onset is earlier in men (peak 20–28 yrs) than women (peak 26–32 yrs). The later/bimodal female onset is attributed in part to a protective estrogen effect (a dopaminergic modulator).
• Incidence: ~0.5–5.0 per 10,000/yr, with geographic variation — higher in those born in urban areas of industrialized nations (per Gajdos/Debrecen lecture).
• Heritability: ~70–80% of liability is genetic — one of the most heritable psychiatric disorders — yet concordance is incomplete, proving environment is necessary.
• Key etiologic risk factors (preview): family history; obstetric complications; winter/late-winter birth; prenatal infection; cannabis use; urban birth/upbringing; migration; childhood trauma; advanced paternal age.

The Gajdos lecture stresses that the genes raising schizophrenia risk are non-specific — they also raise risk for other psychoses (e.g., bipolar disorder). This is the "shared genetic liability" point.

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