EARLY EXPERIENCE, STRESS NEUROBIOLOGY AND PREVENTION SCI

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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. The emotional alterations of abused animals seem enduring, since we detected inappropriate fear responses (either excessive freezing in females, or "fearless" behaviors in the males) at later ages, during the adolescent period. The high impulsivity detected in abused males was associated with low levels of the CSF serotonin metabolite 5-HIAA. In the period covered by the current Progress Report (2006-2007) we have characterized the immune function of the animals, detecting a strong association between neglect experienced as infants and increased levels of inflammatory markers (MAPK p-p38), which is of significant relevance because it links early adverse stress with somatic disorders later in life, in addition to psychopathology. We are currently still collecting other longitudinal data, including: a) measures of growth and metabolism; and b) measures of neurodevelopment, using in vivo neuroimaging techniques (structural MRI and DTI): we have finished collection of MRI and DTI scans and are currently analyzing the data.