Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia

Abstract

MANY HAVE hypothesized that prenatal exposure to infectious agents may increase the risk of schizophrenia. If such an association exists, the risk of schizophrenia might increase with the number of older siblings a child has (ie, birth order). This rationale is based on findings from several studies that the risk of a large variety of common infections is likely to increase with the number of children in the family.^1-7 Thus, the more siblings a person has while in utero, the more likely that a sibling would introduce common infections into the family and thereby increase the risk of maternal infection. An association between birth order and the risk of schizophrenia was reported in a study by Sham et al,⁸ who in particular found that the risk was increased in subjects with siblings who were 3 to 4 years older. However, results from studies on family structure have been inconsistent,^9-17 which may be explained in part by the methods used. Lack of appropriate reference groups has been a major concern in many of these studies, particularly in studies that lacked an actual control group but instead generated an internal comparison group based on the sibship constellations of cases only. Such a procedure may introduce serious bias because of changes in birth rate and family size over time.^18-21