EARLY EXPERIENCE, STRESS NEUROBIOLOGY AND PREVENTION SCI

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本项目目的：研究婴儿虐待和忽视对恒河猴行为发育和下丘脑-垂体-肾上腺（HPA）系统的影响。该系统调节的改变（功能亢进和功能低下）与成年灵长类动物的情感和生理障碍有关。我们正在研究婴儿虐待对以下方面的影响：1)HPA轴功能：基础活动，对心理压力的反应，以及社会或母亲线索如何“缓冲”它；2)情绪行为（恐惧，焦虑）；3)行为和神经内分泌改变背后的神经基质（例如CRF系统的分析）。到目前为止，我们已经发现了高基础皮质醇和早期痛苦的行为迹象（当滥用率高时），随后是老年HPA功能的代偿性下调。我们最近分析了动物在青春期情绪行为和下丘脑轴功能的长期变化。为此，受虐待和配对的对照猕猴被暴露在不同威胁强度的新刺激下。受虐待的幼崽，尤其是雄性，在靠近引起恐惧的物体（如蛇）或触摸物体时，表现出较短的获取食物奖励的潜伏期，与对照组相比，表现出不适当的恐惧反应和更高的攻击性。这种高冲动性与脑脊液5-羟色胺代谢物5-HIAA水平低有关。然而，与对照组相比，受虐待的雌性在面对新事物时表现出更强的防御性和顺从性，这表明婴儿虐待对男性和女性对新刺激的行为反应的长期影响不同。我们正在对动物进行纵向跟踪，包括目前使用结构MRI和DTI进行的生长、代谢和免疫功能以及体内神经发育的研究。

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.