EARLY EXPERIENCE, STRESS NEUROBIOLOGY AND PREVENTION SCI

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本项目的目标：研究婴幼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。在成年灵长类动物中，这一系统的调节变化(包括功能亢进和功能低下)与情感和生理障碍有关。我们正在研究虐待婴儿对以下方面的影响：1)HPA轴功能：基础活动、对心理压力的反应以及社会或母体暗示对其进行缓冲的程度；2)情绪行为(恐惧、焦虑)；3)行为和神经内分泌变化的神经基础(例如对CRF系统的分析)。到目前为止，我们已经检测到了高基础皮质醇和早期(虐待发生率高)的行为痛苦迹象，随后在以后的年龄中，HPA功能出现了补偿性下调。我们最近分析了动物在青春期过程中情绪行为和HPA轴功能的长期变化。为此，受虐和配对的对照猕猴被暴露在不同威胁强度的新刺激下。受虐待的青少年，特别是男性，在提取引起恐惧的物体(如蛇)附近的食物奖励或触摸物体时潜伏期较短，表现出不适当的恐惧反应和比对照组更高的攻击性。这种高冲动性与低水平的脑脊液5-羟色胺代谢产物5-HIAA有关。然而，受到虐待的雌性比对照雌性对新对象更具防御性和顺从性，这表明婴儿虐待对男性对新刺激的行为反应的长期影响不同于女性。我们正在纵向跟踪动物，包括目前对生长、新陈代谢和免疫功能的研究，以及使用结构磁共振和DTI的体内神经发育。

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.