This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Goal of this project: to study the impact of infant abuse and neglect on the development of behavior and the hypothalamic-pituitary-adrenal (HPA) system in rhesus monkeys. Altered regulation of this system (both hyper- and hypo-functioning) is associated with affective and physiological disorders in adult primates. We are studying the effects of infant maltreatment on: 1) HPA axis functionality: basal activity, reactivity to psychological stress and how well social or maternal cues 'buffer' it, 2) emotional behavior (fear, anxiety), 3) the neural substrates underlying the behavioral and neuroendocrine alterations (e.g. analysis of CRF systems). So far we have detected high basal cortisol and behavioral signs of distress at early ages (when abuse rates are high) followed by a compensatory down regulation of HPA function at later ages. We have recently analyzed long-term alterations on emotional behavior and HPA axis function as the animals go through adolescence. For this, maltreated and matched control macaques were exposed to novel stimuli of varying threatening intensities. Maltreated juveniles, particularly males, exhibited shorter latencies to retrieve food rewards adjacent to fear-evoking objects (e.g. snake), or to touch the object, demonstrating inappropriate fear responses and higher aggressiveness in comparison to controls. This high impulsivity was associated with low levels of the CSF serotonin metabolite 5-HIAA. Maltreated females, however, were more defensive and submissive than control females towards the novel objects, indicating different long-term effects of infant maltreatment on behavioral reactivity to novel stimuli in males than in females. We are following the animals longitudinally, including current studies of growth, metabolism and immune function, as well as in vivo neurodevelopment using structural MRI and DTI.
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