Background: Previous work suggests that the association between urbanicity and schizophrenia may be greatest in those with pre-existing vulnerability.
Aims: To test for synergism in risk of schizophrenia between population density and a combined exposure of poor premorbid social and cognitive functioning.
Method: For 371 603 adolescent males examined by the Israeli Draft Board on social and cognitive functioning, data on population density of place of residence and later hospitalisation for schizophrenia were obtained from population-based registries.
Results: There was an interaction between population density (five levels) and poor premorbid social and cognitive functioning (interaction chi(2)=4.6, P=0.032). The adjusted increase in cumulative incidence associated with one unit change in population density was 0.10% in the vulnerable group (95% CI 0.019-0.18, P=0.015), nine times larger than that in the non-vulnerable group (0.011%, 95% CI 0.0017-0.020, P=0.021).
Conclusions: Risk of schizophrenia may increase when people with a genetic liability to the disorder, expressed as poor social and cognitive functioning, need to cope with city life.