Clinical Psychobiology

早期的不良经历，如童年虐待、忽视和失去父母，已被确定为成年后发展为抑郁症、某些焦虑症，或许还有其他障碍的风险因素。我们在之前的资助期间证明，有儿童期性虐待或身体虐待史的妇女对心理社会实验室压力的下丘脑-垂体-肾上腺(HPA)轴和自主神经反应显着增加，这种影响在遭受虐待的妇女中最为明显。 目前的抑郁症。我们随后展示了HPA轴的多个水平的变化，包括中枢神经系统，这些变化共同可能导致对压力的敏感性增加和精神病理的表现，特别是在应对额外的压力暴露时。这项拟议项目的目标是确认和扩大这些发现，重点是进一步表征ELS的神经生物学后果，确定可能缓和或调节ELS后人类对应激的易感性增加的因素，并扩大我们的样本以包括男性受试者。我们将确定ELS发生时的年龄和ELS的特征是否影响对标准化心理社会的反应 对患有和不患有MDD的患者进行实验室应激源和标准神经内分泌激发试验。我们将进一步确定ELS和青春期/成年期创伤应激的相互作用是否影响这些受试者的神经内分泌反应。我们还将确定ELS对神经内分泌反应性的影响是否存在性别差异，以及ELS的影响是否受到已知影响与生活压力相关的精神病理学表现的基因多态性的影响。它的特殊性 我们之前对抑郁症患者的观察也将通过评估有和没有ELS病史的社交焦虑症(SAD)患者的神经内分泌功能，并将这些结果与有或没有ELS病史的新的重度抑郁症患者的结果进行比较，来扩展我们之前对抑郁症患者的观察。最后，由于抑郁症的认知功能障碍在很大程度上仍然是一个未被探索的研究领域，我们将试图确定患有和不患有抑郁症或SAD的患者的ELS对认知功能的影响，即知觉、注意力、记忆和 问题解决，以及认知障碍的严重程度是否与HPA轴反应有关，以及ELS的时间和类型、成年创伤、性别和精神病理。该项目还将作为确定和描述将在项目0009(米勒，PI)、0006(戴维斯，PI)、0012(梅贝格，PI)和0013(Kilts，PI)中进行评估的个人的受试者的核心。

Early adverse experiences, such as childhood abuse, neglect and parental loss, have been firmly established as risk factors for the development of depression, certain anxiety disorders, and perhaps other disorders, in adulthood. We demonstrated during the previous funding period that women with a history of childhood sexual or physical abuse exhibit markedly increased hypothalamic-pituitary-adrenal (HPA) axis and autonomic responses to psychosocial laboratory stress and this effect was most pronounced in those abused women who suffered from current depression. We subsequently demonstrated alterations at multiple levels of the HPA axis, including the CNS, which together likely contribute to the increased sensitivity to stress and the manifestation of psychopathology, particularly in response to additional stress exposure. The objective of this proposed project is to confirm and extend these findings with a focus on the further characterization of the neurobiological consequences of ELS, identification of factors that might moderate or mediate increased vulnerability to stress after ELS in humans, and to expand our sample to include male subjects. We will determine whether age at the time of the ELS, and characteristics of the ELS influence responsiveness to a standardized psychosocial laboratory stressor and to a standard neuroendocrine challenge test in individuals with and without MDD. We will further determine whether the interaction of ELS and adolescent/adulthood trauma stress influences neuroendocrine reactivity in these subjects. We will also determine whether there are sex differences in the effects of ELS on neuroendocrine reactivity and whether the effects of ELS are moderated by polymorphisms of genes that are known to influence the manifestation of psychopathology in relation to life stress. The specificity of our previous observations in patients with depression will also be expanded by assessing neuroendocrine function in patients with social anxiety disorder (SAD) with and without a history of ELS, and by comparing these results to those of a new cohort of patients with major depression with and without ELS. Finally, because cognitive dysfunction in depression remains a largely unexplored research area, we will seek to determine the impact of ELS in patients with and without depression or SAD on cognitive function, i.e. perception, attention, memory, and problem solving, and whether the severity of cognitive impairment is related to HPA axis reactivity, as well as the timing and type of ELS, adulthood trauma, gender and psychopathology. This project will also serve as a human subjects core for the identification and description of individuals that will undergo assessments in Projects 0009 (Miller,PI), 0006 (Davis, PI), 0012 (Mayberg, PI) and 0013 (Kilts, PI).