Evidence of a dose-response relationship between urbanicity during upbringing and schizophrenia risk

Background: Many studies have demonstrated that an urban birth or upbringing increases schizophrenia risk, but no studies have been able to distinguish between these effects. The objectives of this study were to discriminate the effect of urbanicity at birth from an effect of urbanicity during upbringing, and to identify particularly vulnerable age periods and a possible dose-response relationship between urbanicity during upbringing and schizophrenia risk. Methods: Using data from the Danish Civil Registration System, we established a population-based cohort of 1.89 million people, which included information on place of birth, place of residence during upbringing, and the accumulated number of years lived in each category of the 5-level degree of urbanization during upbringing. Schizophrenia in cohort members and mental illness in a parent or sibling were identified by linkage with the Danish Psychiatric Central Register. Results: Individuals living in a higher degree of urbanization than 5 years earlier had a 1.40-fold (95% confidence interval, 1.28-1.51) increased risk, while individuals living in a lower degree of urbanization than 5 years earlier had a 0.82-fold (95% confidence interval, 0.77-0.88) decreased risk of schizophrenia. For fixed urbanicity at the 15th birthday, risk increased with increasing degree of urbanization at birth. Furthermore, the more years lived in the higher the degree of urbanization, the greater the risk Individuals who lived their first 15 years in the highest category of the 5-level urbanicity had a 2.75-fold (95% confidence interval, 2.31-3.28) increased risk of schizophrenia. Conclusions: Continuous, or repeated, exposures during upbringing that occur more frequently in urbanized areas may be responsible for the association between urbanization and schizophrenia risk.