Prenatal Risk Factors in Schizophrenia
By Alan S. Brown, M.D., and Ezra S. Susser, M.D., Dr. P.H. |
January 1, 1996
Dr. Brown is assistant professor of psychiatry at Columbia University and associate director of the Division of Epidemiology and Community Psychiatry at New York State Psychiatric Institute.
Dr. Susser is associate professor of psychiatry at Columbia University and director of the Division of Epidemiology and Community Psychiatry at New York State Psychiatric Institute.
Perinatal traumatic events, such as obstetric complications (OCs), can cause brain damage in the newborn and may also contribute to the etiology of neurodevelopmental disorders. In particular, perinatal trauma is proposed to contribute to the etiology of cerebral palsy (Nelson and Ellenberg) and mental retardation (Broman).
Associations between the number and/or severity of obstetric complications and the risk of schizophrenia in the offspring have been reported in many studies (McNeil and Kaij; Lewis and Murray); several indicators of prenatal or perinatal insults, including decreased head circumference, low birth weight or respiratory difficulty, appear to occur more frequently in infants who developed schizophrenia in adulthood compared to controls (McNeil and Kaij). These studies, however, relied upon retrospective data, which are subject to inaccurate reporting of events and recall bias. Indeed, the only study of OCs and schizophrenia in which obstetric histories were prospectively collected did not replicate the association between OCs and schizophrenia (Done and others).
It is clear that much research work remains as we attempt to further elucidate the role of prenatal risk factors in schizophrenia. Our group has embarked upon a series of exciting collaborative birth cohort studies aimed at uncovering these neurodevelop-mental etiologies using novel approaches and strategies. These investigations are designed to address the limitations of prior studies, which include crude prenatal exposure data, inadequate control of bias due to loss to follow-up, and inadequate statistical power. As an illustration, we shall briefly describe the most advanced of these studies, the Prenatal Determinants of Schizophrenia (PDS) study.
The PDS study is based on the California Child Health and Development Study (CHDS), which included almost 20,000 live births from 1959 to 1966 in Oakland, Calif. The primary goal of the PDS is to examine relationships between specific prenatal exposures and the later development of schizophrenia in cohort members. A unique feature of this study is the availability of serum samples drawn during the pregnancies of the mothers of cohort members. The analysis of these serum samples will provide us with an opportunity to precisely quantify the nature and degree of a variety of putative prenatal exposures, and relate them to the occurrence of schizophrenia in the offspring. For example, Hollister and others (in press) have reported an association between Rh incompatibility and schizophrenia; we will attempt to replicate this finding in the PDS cohort.
We plan to utilize precise data on prenatal exposures from the PDS study in conjunction with family history and other genetic data from PDS families. Gene-environment studies that we plan to initiate include a suspected interaction between prenatal folate intake and a genetic abnormality of folate metabolism in the pathogenesis of schizophrenia.
For many years, researchers have proposed that schizophrenia might have neurodevelopmental etiologies, and hypothesized that several prenatal environmental factors could be potential causal agents. However, we have only recently witnessed the emergence of epidemiologic evidence implicating specific prenatal risk factors in schizophrenia. We are now on the threshold of the next phase of research in this field, in which sophisticated new designs will yield increasingly precise data on the gestational environmental exposures, opening new vistas for epidemiologic research on the causes of schizophrenia.
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