Prenatal Infection and Adult Schizophrenia

Evidence for the role of prenatal viral infection in the etiology of schizophrenia is growing. Although most of the attention in this research domain has focused on prenatal exposure to influenza (see the preceding article by Bagalkote, Pang, & Jones), there are two compelling reasons to consider other viral pathogens as plausible risk factors for schizophrenia. First, a number of gestational viral infections, such as rubella, cytomegalovirus, and herpes simplex virus, are known causes of developmental central nervous system (CNS) malformations [1]; and several of these abnormalities and their manifestations are, in many cases, concordant with findings in schizophrenia. In this respect, these infections are more plausible as risk factors for schizophrenia than influenza, a virus that has not been clearly established as a CNS teratogen. Second, as discussed below, some infections other than influenza are more compatible with the well-replicated finding of increased winter/spring births in schizophrenia [2]. If influenza, which peaks in the winter months, accounts for the season-of-birth effect in schizophrenia, then third-trimester or neonatal exposure to this virus should be associated with an increased risk of schizophrenia; however, most studies on influenza report a second-trimester association. In this article I shall first review the neurodevelopmental hypothesis of schizophrenia, which forms our conceptual basis for the examination of prenatal risk factors for this disorder. I shall then discuss in detail our strategy for identifying potential viral candidates for schizophrenia, which includes consideration of the plausibility of these agents as causes of developmental neuropathology. Following that section, I shall review the major epidemiologic studies aimed at linking noninfluenza prenatal infectious exposures with schizophrenia, including several