EARLY EXPERIENCE, STRESS NEUROBIOLOGY AND PREVENTION SCI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目标：研究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。该系统的调节改变（功能亢进和功能减退）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的神经基质（例如CRF系统的分析）。到目前为止，我们已经检测到高基础皮质醇和早期（滥用率高时）痛苦的行为迹象，随后是后期HPA功能的补偿性下调。虐待动物的情绪变化似乎是持久的，因为我们发现不适当的恐惧反应（无论是过度冻结的女性，或“无畏”的行为在男性）在以后的年龄，在青少年时期。在受虐待男性中检测到的高冲动性与CSF 5-羟色胺代谢物5-HIAA的低水平相关。在当前进展报告（2006-2007）所涵盖的时期内，我们对动物的免疫功能进行了表征，检测到婴儿期忽视与炎症标志物（MAPK p-p38）水平升高之间存在强烈关联，这具有重要意义，因为它将早期不良应激与以后生活中的躯体疾病以及精神病理学联系起来。我们目前仍在收集其他纵向数据，包括：a）生长和代谢的测量;和B）神经发育的测量，使用体内神经成像技术（结构MRI和DTI）：我们已经完成了MRI和DTI扫描的收集，目前正在分析数据。

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.