There is evidence that prenatal stress may have a number of adverse effects on the offspring of gestationally-stressed mammalian mothers. Human studies, while problematic, have associated prenatal stress with developmental and cognitive delays and emotionality, and prenatal adverse experience has been implicated in vulnerability to early schizophrenia and other forms of childhood psychopathology. Evidence from rodents also indicates that prenatal stress may have a variety of deleterious effects on offspring which are associated with risk for psychopathology in humans, such as developmental delays, cognitive deficits, increased emotionality and responsivity to stress, social behavior decrements, and functional alteration of HPA axis and brain neurotransmitter systems. Recent studies have demonstrated similar effects in prenatally stressed primate infants. These effects are attributed to activation of the HPA axis in the stressed pregnant female and subsequent neurotoxic effects of maternal glucocorticoids on the fetus. However, few studies have utilized more precise manipulations of the HPA axis during gestation. Evidence indicates that gestational treatment with HPA axis hormones may have direct physiological consequences in the fetus and similar post-natal effects to those observed in prenatally-stressed infants. Preliminary findings also showed long-term alterations in social behavior in offspring of mothers that received exogenous HPA axis stimulation during pregnancy. More direct manipulation of the HPA axis would clarify the role of this system in mediating the effects observed while controlling for individual differences in stress perception and responsivity. Such studies also have implications for the clinical use of corticosteroids in pregnant women, in which corticosteroids are prescribed for treatment of neonatal respiratory problems. The proposed research will examine the effects of maternal HPA axis stimulation via ACTH administration on stress responsivity, social behavior, and cognitive functioning in offspring of ACTH-treated and control mothers in a primate model. This investigation will replicate and extend previous findings from prenatally-stressed primate infants and further clarify the role of the HPA axis in mediating these effects in the most long-term follow-up of the effects of any prenatal manipulation in a nonhuman primate to date.
