Abstract

Background In Northern Europe, several studies have indicated that people born and raised in urban areas have an increased risk of psychosis. Emerging research in the Global South has produced more heterogeneous and inconsistent findings, suggesting that the impact of urban environments on psychosis risk may depend on social context and broader environmental factors at multiple levels. Methods We constructed a cohort of 5,137,561 individuals born in Chile (1992-2012) using the national first episode psychosis (FEP) and Birth and Death registries. We identified 14,410 individuals with nonaffective FEP (ICD-10 F20-F29) recorded between 2005 and 2022. Urbanicity at birth (urban vs rural) was our main exposure. We estimated incidence rate ratios (IRRs) via Poisson regression, adjusting for year of birth and region to account for birth-cohort effects. We also examined whether parental education and employment-two indicators of social deprivation-modified this association. Findings Over similar to 92 million person-years, the crude incidence rate was 15.67 per 100,000 person-years (95% CI: 15.42, 15.93). No overall association between urbanicity at birth and non-affective FEP was found after accounting for social factors (adjusted IRR = 0.96, 95% CI: 0.91, 1.01). However, parental low education appeared to modify the association between urbanicity and psychosis on both multiplicative and additive scales, with an additive interaction (RERI = 0.33, 95% CI: 0.18, 0.47), supporting a model where urbanicity increases psychosis risk primarily in the presence of social deprivation. Interpretation Urban birth alone was not associated with higher FEP incidence in Chile, but an elevated risk was seen among families with lower educational attainment in urban areas. This suggests a causal interplay between urbanicity and social deprivation, underscoring the importance of multilevel frameworks for understanding psychosis risk, especially in rapidly urbanizing societies.