We examined the relationship between the dates of births of schizophrenic patients admitted to hospitals for the first time in England and Wales between 1970 and 1979, and the occurrence of influenza epidemics between 1939 and 1960. Our results indicate that exposure to influenza epidemics between the third and seventh month of gestation is associated with schizophrenia in adult life. The hypothesis that maternal viral infection is an important cause of schizophrenia can explain many aspects of the enigmatic epidemiology of the condition.

The epidemiological evidence that the offspring of women exposed to influenza in pregnancy are at increased risk of schizophrenia is conflicting. In an attempt to clarify the issue we explored the relationship between the monthly incidence of influenza (and measles) in the general population and the distribution of birth dates of three large series of schizophrenia patients--16,960 Scottish patients born in 1932-60; 22,021 English patients born in 1921-60; and 18,723 Danish patients born in 1911-65. Exposure to the 1957 epidemic of A2 influenza in midpregnancy was associated with an increased incidence of schizophrenia, at least in females, in all three data sets. We also confirmed the previous report of a statistically significant long-term relationship between patients' birth dates and outbreaks of influenza in the English series, with time lags of -2 and -3 months (the sixth and seventh months of pregnancy). Despite several other negative studies by ourselves and others we conclude that these relationships are probably both genuine and causal; and that maternal influenza during the middle third of intrauterine development, or something closely associated with it, is implicated in the aetiology of some cases of schizophrenia.

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