Project Summary

Dolores Malaspina, M.D., M.S.P.H. (Distinguished Investigator 2007) of New York University, aims to study how prenatal glucocorticoid excess at different gestational ages may increase the risk of a number of different psychiatric illnesses. Nutritional, infectious, metabolic and other maternal and fetal conditions can prompt a glucocorticoid response, but severe maternal threat can do so without medical conditions. Therefore, maternal glucocorticoids may be a common pathway linking a variety of insults to the risk for psychiatric disorders. The mechanism may work by neurogenesis disruption at critical periods, and/or by altering sensitivity to stress, i.e. by fetal programming. Many primate and rodent models support this idea, but until now it has not been possible to study the consequences of severe stress in humans, either at critical gestational windows, or divorced from other effects (e.g. famine) in a prospective well controlled population study. Such a study is now possible because of a "natural" experiment in which a stress exposure (war) was "administered" to -450 pregnant women during each gestational month: The Six Day War occurred during a prospective population study of 90,000 births; >4,000 had in utero war exposure. In the proposed NARSAD study, Dr. Malaspina will use this resource to study the relationship between the specific gestational age of the prenatal war stress and psychiatric disorders. Preliminary analysis links schizophrenia risk to the second month, but excess risk for other psychiatric diseases peaks at 12 weeks, 15 weeks, and at later gestational ages and may be sex specific. She aims to further describe the pregnancy outcomes, neonatal health, birth defects, adolescent intelligence test scores, and individual clinical features for the psychiatric conditions (including autism, affective disorders, substance abuse, and dyslexia, ADHD and epilepsy) by gestational age. She will compare the babies born in the year before and after war stress occurred. Findings should yield a better understanding of the temporal sequence of the cellular events occurring during neurodevelopment that are associated with specific neuropsychiatric outcomes.

Program Area: MULTIPLE FOCUS\Autism/Mood Disorders/Schizophrenia

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