Does population density and neighborhood deprivation predict schizophrenia? A nationwide Swedish family-based study of 2.4 million individuals.

People living in densely populated and socially disorganized areas have higher rates of psychiatric morbidity, but the potential causal status of such factors is uncertain. We used nationwide Swedish longitudinal registry data to identify all children born 1967-1989 (n = 2361585), including separate datasets for all cousins (n = 1715059) and siblings (n = 1667894). The nature of the associations between population density and neighborhood deprivation and individual risk for a schizophrenia diagnosis was investigated while adjusting for unobserved familial risk factors (through cousin and sibling comparisons) and then compared with similar associations for depression. We generated familial pedigree structures using the Multi-Generation Registry and identified study participants with schizophrenia and depression using the National Patient Registry. Fixed-effects logistic regression models were used to study within-family estimates. Population density, measured as ln(population size/km(2)), at age 15 predicted subsequent schizophrenia in the population (OR = 1.10; 95% CI: 1.09; 1.11). Unobserved familial risk factors shared by cousins within extended families attenuated the association (1.06; 1.03; 1.10), and the link disappeared entirely within nuclear families (1.02; 0.97; 1.08). Similar results were found for neighborhood deprivation as predictor and for depression as outcome. Sensitivity tests demonstrated that timing and accumulation effects of the exposures (mean scores across birth, ages 1-5, 6-10, and 11-15 years) did not alter the findings. Excess risks of psychiatric morbidity, particularly schizophrenia, in densely populated and socioeconomically deprived Swedish neighborhoods appear, therefore, to result primarily from unobserved familial selection factors. Previous studies may have overemphasized the etiological importance of these environmental factors.