Schizophrenia and the influenza epidemics of 1957 in Japan

Background: We tested the hypothesis that the exposure to an influenza epidemic during the second trimester of gestation is associated with an increased risk of later development of schizophrenia. Methods: There were three influenza epidemics (A/B mixed type, the first A2 type and the second A2 type) in 1957 in Kochi, Japan. We compared the risk of developing schizophrenia in birth cohorts exposed to these three influenza epidemics during gestation with that in birth cohorts not exposed. To identify subjects who had developed schizophrenia, we surveyed patients with schizophrenia who received medical care at all psychiatric institutions in Kochi prefecture. Results: There is a pattern that schizophrenic births increase twice or more among female subjects who were exposed to each of three influenza epidemics in the fifth month of gestation. The increase in the female births exposed to the second A2 epidemic was significant (relative risk 2.86, 95% confidence interval 1.37–5.26). This pattern across the three epidemics was not observed in male subjects. Conclusions: Prenatal exposure to an influenza epidemic during the second trimester increased the risk of later development of schizophrenia in female births.