BIOLOGY OF RISK AND PTSD IN HOLOCAUST SURVIVOR OFFSPRING

大屠杀幸存者后代的风险生物学和创伤后应激障碍

• 批准号: 7380515
• 负责人: RACHEL YEHUDA
• 金额: $ 2.68万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380515
• 关键词: child rearing; parents; trauma; child rearing; parents; trauma

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

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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。在大屠杀幸存者的后代中，将父母PTSD确定为PTSD的危险因素，我们可以开始研究PTSD风险的生物学相关性。尽管当然还有其他研究PTSD中风险的方法，例如在可能会遇到极端创伤的人中研究特征（例如，消防员，部署的士兵），这些人的状况为“有PTSD风险”的地位是基于预测的创伤。相比之下，就父母PTSD的后代而言，对PTSD的脆弱性是基于在后代对焦点创伤的经验之前的历史变量。通过将有或没有PTSD的高风险后代与没有父母PTSD的危险因素的后代进行比较，可以解决与PTSD相关的生物变量是否与与脆弱性相关的生物变量相似。另外，通过将大屠杀幸存者后代与父母不接触大屠杀的受试者进行比较，可以考虑与父母中与极端创伤（即大屠杀）相关的非特异性“转世”效应。 我们的研究集中在两个主要的神经内分泌系统上：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，非暴露受试者以及患有其他精神疾病的人相比，患有PTSD的创伤幸存者之间的创伤幸存者之间存在显着差异。我们已经提出，这些发现可以解释为反映了PTSD中HPA轴的负面反馈抑制。相反，抑郁症的HPA轴改变已被解释为反映了皮质醇的负反馈抑制减少。拟议研究提供的风险的机会将扩大我们与PTSD相关性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。对危险因素的研究最终可能有助于解决为什么有些人将PTSD症状发展为降低幅度事件的问题，而其他人也无法发展这种疾病，即使响应极高的事件，例如大屠杀。最后，鉴定PTSD生物危险因素可能会提供预防，预防和早期治疗的见解