BIOLOGY OF RISK AND PTSD IN HOLOCAUST SURVIVOR OFFSPRING

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。在大屠杀幸存者的后代中，父母的PTSD是PTSD的一个危险因素，我们已经能够开始检查PTSD风险的生物学相关性。虽然肯定有其他方法来研究创伤后应激障碍的风险，如研究可能暴露于极端创伤的人的特征（例如，消防员、部署的士兵），这些人的PTSD“风险”状态是基于预测的创伤暴露。与此相反，在后代与父母的创伤后应激障碍的情况下，创伤后应激障碍的脆弱性是基于一个历史变量之前，是独立的，后代的经验，一个局灶性创伤。通过比较有和没有PTSD的风险后代与没有父母PTSD风险因素的后代，有可能解决与PTSD相关的生物学变量是否与脆弱性相关的生物学变量相似。通过额外比较大屠杀幸存者后代与其父母未暴露于大屠杀的受试者，有可能解释与极端创伤暴露相关的非特异性“跨代”效应（即，大屠杀）的父母。 我们的研究集中在两个主要的神经内分泌系统-下丘脑-垂体-肾上腺（HPA）轴和交感神经系统（SNS）。我们已经开发了一系列神经内分泌评估，与没有PTSD的幸存者、非暴露受试者和患有其他精神疾病，特别是重度抑郁症（MDD）的人相比，PTSD创伤幸存者之间存在显著差异。我们提出，这些发现可以解释为反映了增强的负反馈抑制HPA轴的PTSD。相反，抑郁症的HPA轴改变被解释为反映了皮质醇负反馈抑制的减少。这些研究提供的检查风险的机会将放大我们形成关于PTSD相关因素之间相互关系的结论的能力，因为它们与脆弱性、暴露和疾病有关，因此对于理解PTSD的病理生理学至关重要。风险因素的研究可能最终有助于解决为什么有些人发展PTSD的症状，以较低的规模事件的问题，而其他人没有发展这种疾病，即使在响应极高的规模，如，例如，大屠杀。最后，识别PTSD的生物学危险因素可能为预防、预防和早期治疗这种疾病提供见解

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. Having identified parental PTSD as a risk factor for PTSD among offspring of Holocaust survivors, we are in a position to begin to examine biological correlates of risk for PTSD. Although there are certainly other approaches to studying risk in PTSD, such as studying characteristics in persons that are likely to be exposed to extreme trauma (e.g., firefighters, deployed soldiers), the status of such persons as "at risk" for PTSD is based on predicted trauma exposure. In contrast, in the case of offspring with parental PTSD, the vulnerability to PTSD is based on a historical variable that precedes, and is independent of, the offspring's experience of a focal trauma. By comparing at-risk offspring with and without PTSD, to offspring without the risk factor of parental PTSD, it is possible to address whether the biological variables associated with PTSD are similar to those associated with vulnerability. By additionally comparing Holocaust survivor offspring with subjects whose parents were not exposed to the Holocaust, it is possible to account for nonspecific 'transgenerational' effects related to extreme trauma exposure (i.e., the Holocaust) in parents. Our studies have focused on two major neuroendocrine systems -- the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). We have developed a battery of neuroendocrine assessments that have demonstrated significant differences between trauma survivors with PTSD when compared with survivors without PTSD, non-exposed subjects, and persons with other psychiatric disorders, particularly major depressive disorder (MDD). We have proposed that these findings can be explained as reflecting an enhanced negative feedback inhibition of the HPA axis in PTSD. In contrast, HPA axis alterations in depression have been explained as reflecting a reduced negative feedback inhibition of cortisol. The opportunity of examining risk provided by the proposed studies will magnify our ability to form conclusions about interrelationships among correlates of PTSD as they relate to vulnerability, exposure, and illness, and is therefore critical to understanding the pathophysiology of PTSD. The study of risk factors may ultimately help address the issue of why some individuals develop the symptoms of PTSD to lower magnitude events, whereas others fail to develop this disorder even in response to events of extremely high magnitude, such as, for example, the Holocaust. Finally, the identification of biological risk factors for PTSD may provide insights into prevention, prophylaxis and early treatment of this condition