Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data

Neighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60-71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20-0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R(2)=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs