Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia

A BSTRACT Background Although a family history of schizophrenia is the best-established risk factor for schizophrenia, environmental factors such as the place and season of birth may also be important. Methods Using data from the Civil Registration System in Denmark, we established a populationbased cohort of 1.75 million persons whose mothers were Danish women born between 1935 and 1978. We linked this cohort to the Danish Psychiatric Central Register and identified 2669 cases of schizophrenia among cohort members and additional cases among their parents. Results The respective relative risks of schizophrenia for persons with a mother, father, or sibling who had schizophrenia were 9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95 percent confidence interval, 5.10 to 10.16), and 6.99 (95 percent confidence interval, 5.38 to 9.09), as compared with persons with no affected parents or siblings. The risk of schizophrenia was associated with the degree of urbanization of the place of birth (relative risk for the capital vs. rural areas, 2.40; 95 percent confidence interval, 2.13 to 2.70). The risk was also significantly associated with the season of birth; it was highest for births in February and March and lowest for births in August and September. The population attributable risk was 5.5 percent for a history of schizophrenia in a parent or sibling, 34.6 percent for urban place of birth, and 10.5 percent for the season of birth. Conclusions Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis. (N Engl J Med 1999;340:603-8.)