Influenza in Early Pregnancy Linked to Schizophrenia

Laurie Barclay, MD

August 02, 2004

Aug. 2, 2004 — Influenza in early pregnancy may be associated with schizophrenia, according to the results of a nested case-control study published in the August issue of the Archives of General Psychiatry. The investigators suggest that an antibody response, rather than infection, may explain this association.

"Some, but not all, previous studies suggest that prenatal influenza exposure increases the risk of schizophrenia," write Alan S. Brown, MD, from New York State Psychiatric Institute in New York City, and colleagues. "Discrepant findings may have resulted from exposure misclassification."

From a large cohort born from 1959 through 1966 and followed up 30 to 38 years later for psychiatric disorders, the investigators identified 64 members with schizophrenia spectrum disorders. Control subjects were 125 members matched for date of birth, sex, length of time in the cohort, and availability of maternal serum for influenza antibody testing.

Influenza exposure during the first trimester increased the risk of schizophrenia sevenfold, but exposure during the second or third trimester did not affect risk. Exposure during early to midpregnancy increased the risk of schizophrenia threefold. Adjustment for potential confounders did not affect these results.

Study limitations include use of a proxy measure of influenza exposure and of serum samples frozen for more than 30 years, and lack of data on family history of schizophrenia.

"These findings represent the first serologic evidence that prenatal influenza plays a role in schizophrenia," the authors write. "If confirmed, the results may have implications for the prevenion of schizophrenia and for unraveling pathogenic mechanisms of the disorder.... Although the precise mechanisms need to be delineated, it may be worth considering the question of routine vaccination of nonpregnant women, given the possibility that the antibody response to influenza, rather than direct infection, may be resposible for the observed increase in risk of schizophrenia."

The National Alliance for Research on Schizophrenia and Depression, the National Institutes of Mental Health, and the National Institutes of Health helped support this study, along with various private foundations.

Arch Gen Psychiatry. 2004;61:774-780

Reviewed by Gary D. Vogin, MD


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