EARLY EXPERIENCE, STRESS NEUROBIOLOGY AND PREVENTION SCI

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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亲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(如CRF系统分析)。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。受虐动物的情绪变化似乎是持久的，因为我们在青春期的晚年发现了不适当的恐惧反应(雌性动物的过度冰冻，或者雄性动物的“无所畏惧”行为)。在被虐待的男性中检测到的高冲动与脑脊液5-羟色胺代谢产物5-HIAA的低水平有关。在目前的进展报告所涵盖的时期(2006-2007年)，我们对动物的免疫功能进行了表征，发现婴儿时期经历的忽视与炎症标记物(MAPK p-p38)水平升高之间存在强烈关联，这一点具有重要意义，因为除了精神病理学外，它还将早期不良应激与晚年生活中的躯体疾病联系在一起。我们目前仍在收集其他纵向数据，包括：a)生长和新陈代谢的测量；以及b)使用体内神经成像技术(结构MRI和DTI)测量神经发育：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.