Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys

Background: Early life stress, including during fetal development, has been hypothesized to predispose individuals to several illnesses and psychiatric disorders later in adulthood. Methods: To determine whether prenatal stress alters neural, hormonal, and behavioral processes in nonhuman primates, pregnant rhesus monkeys were acutely stressed on a daily basis for 25% of their 24-week gestation with an acoustical startle protocol. At 2 to 3 years of age, hippocampal volume, neurogenesis in the dentate gyrus, and cortisol levels were evaluated in the offspring generated from stressed and control pregnancies. Results: Prenatal stress, both early and late in pregnancy, resulted in a reduced hippocampal volume and an inhibition of neurogenesis in the dentate gyrus. These changes were associated with increased pituitary-adrenal activity, as reflected by higher cortisol levels after a dexamethasone suppression test, and also with behavioral profiles indicative of greater emotionality. Conclusions: These findings indicate that the prenatal environment can alter behavior, dysregulate neuroendocrine systems, and affect the hippocampal structure of primates in a persistent manner. Biol Psychiatry 2003; 54:1025-1034 (C) 2003 Society of Biological Psychiatry