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

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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。在确定父母 PTSD 是大屠杀幸存者后代 PTSD 的危险因素后，我们可以开始检查 PTSD 风险的生物学相关性。尽管当然还有其他方法来研究 PTSD 风险，例如研究可能遭受极端创伤的人（例如消防员、部署的士兵）的特征，但这些人的 PTSD“风险”状况是基于预测的创伤暴露情况。相比之下，在父母患有创伤后应激障碍 (PTSD) 的后代中，创伤后应激障碍 (PTSD) 的脆弱性是基于一个历史变量，该历史变量先于且独立于后代的局灶性创伤经历。通过比较有或没有 PTSD 的高危后代与没有父母 PTSD 风险因素的后代，可以确定与 PTSD 相关的生物变量是否与与脆弱性相关的生物变量相似。通过另外将大屠杀幸存者后代与父母未遭受大屠杀的受试者进行比较，可以解释与父母遭受极端创伤（即大屠杀）相关的非特异性“跨代”影响。 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）。我们开发了一系列神经内分泌评估，证明患有 PTSD 的创伤幸存者与没有 PTSD 的幸存者、未暴露的受试者以及患有其他精神疾病，特别是重度抑郁症 (MDD) 的人相比，存在显着差异。我们提出，这些发现可以解释为反映了 PTSD 中 HPA 轴负反馈抑制的增强。相比之下，抑郁症中 HPA 轴的改变被解释为反映了皮质醇负反馈抑制的减少。拟议研究提供的检查风险的机会将增强我们对 PTSD 相关因素之间相互关系得出结论的能力，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。对风险因素的研究可能最终有助于解决为什么有些人在发生较小程度的事件时会出现 PTSD 症状，而其他人即使在应对极其严重的事件（例如大屠杀）时也不会出现这种疾病的问题。最后，识别 PTSD 的生物危险因素可能会为这种情况的预防、预防和早期治疗提供见解。