Biology of Risk of PTSD in Holocaust Survivor Offspring

描述(申请人提供)：本申请是基于初步的， 但令人信服的数据表明，父母的创伤后应激障碍可能是 大屠杀幸存者后代中的创伤后应激障碍。数据，在这篇文章中完全描述了 应用，引导我们检查创伤后应激障碍风险的生物学相关性。至 确定是否以及在多大程度上观察到了创伤后应激障碍的生物学改变 都与父母创伤后应激障碍的危险因素有关，我们将比较临床数据 以及具有父母创伤后应激障碍危险因素的个人的生物学数据 那些没有这种风险因素的人。我们还试图区分生物学和 与创伤后应激障碍风险相关的变量以及与 这种疾病的病理生理学。这将通过比较 有创伤后应激障碍危险因素的个人(但没有患上创伤后应激障碍) 那些患上创伤后应激障碍的人。此外，我们建议研究是否 有创伤暴露的父母从未患上创伤后应激障碍的人类似于 父母没有遭受过极端创伤(即大屠杀)的人。 这将允许确定父母是否单独接触 父母的创伤后应激障碍也可能是与生物后遗症相关的危险因素。 最后，我们希望研究人的生物变化是否不同。 伴和不伴抑郁障碍，主要涉及 神经内分泌系统作为创伤后应激障碍，在任何特定条件下有 或者没有父母的创伤后应激障碍，没有自己的创伤后应激障碍，或者父母没有受到创伤。 我们实验室开发的两种神经内分泌刺激测试将是 在每个研究对象中进行测试。小剂量地塞米松抑制试验 (DST)将被用来评估负反馈抑制 下丘脑-垂体-肾上腺(HPA)轴。甲孕酮刺激性试验 (MST)将用于通过以下途径评估甲状腺上激活(例如，CRF释放) 甲孕酮对促肾上腺皮质激素和11-脱氧皮质醇反应的检测 行政管理。在每项测试中，我们将确定淋巴细胞糖皮质激素的特征 受体(GR)数量在基础条件下和对地塞米松的反应 (地塞米松)和甲氧孕酮管理，作为一种获得 GR敏感性(或反应性)指标。我们还将进行时间生物学研究 皮质醇、促肾上腺皮质激素昼夜节律的研究 (ACTH)和去甲肾上腺素(NE)。为了实现这些目标，我们将检查数据 在五年的时间里，从240名受试者中：80名后代的风险因素为 父母创伤后应激障碍，80名没有父母创伤后应激障碍的子女，以及80名人口统计学上的 可比较的受试者(其父母在1935年后不在欧洲)。主题 将被进一步细分，这样每组有40个人，有和没有 创伤后应激障碍；每个亚组中有一半人将患有目前的抑郁障碍。因此，我们 将在12个小组中每组招募20名受试者。

DESCRIPTION (provided by applicant): This application is based on preliminary, but compelling data, implicating parental PTSD as a putative risk factor for PTSD among offspring of Holocaust survivors. The data, fully described in this application, lead us to examine biologic correlates of risk for PTSD. To determine whether and to what extent biological alterations observed in PTSD are related to the risk factor of parental PTSD, we will compare clinical data and biological data in individuals with the risk factor of parental PTSD to those without this risk factor. We also seek to differentiate between biologic variables associated with risk for PTSD and those associated with the pathophysiology of this disorder. This will be accomplished by comparing individuals with the risk factor for PTSD (but have not developed PTSD) with those that have developed PTSD. Further, we propose to study whether individuals with trauma-exposed parents who never developed PTSD are similar to persons whose parents were not exposed to extreme trauma (i.e., the Holocaust). This will allow a determination of whether parental exposure, separate from parental PTSD, might also be a risk factor associated with biologic sequelae. Finally, we wish to study whether biologic alterations are different in persons with and without depressive disorders that principally involve the same neuroendocrine systems as PTSD, under any of the specific conditions of having or not having parental PTSD, one's own PTSD, or parental exposure to trauma. Two neuroendocrine stimulation tests, developed in our laboratory, will be performed in each study subject. The low-dose dexamethasone suppression test (DST) will be used to evaluate negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. The metyrapone stimulation test (MST) will be used to assess suprapituitary activation (e.g., CRF release) via examination of the ACTH and 11-deoxycortisol response to metyrapone administration. In each test, we will characterize lymphocytic glucocorticoid receptor (GR) number under basal conditions, and in response to dexamethasone (DEX) and metyrapone administration, respectively, as a way of obtaining indices of GR sensitivity (or reactivity). We will also perform chronobiologic studies to characterize the circadian rhythm of cortisol, adrenocorticotropin (ACTH) and norepinephrine (NE). To accomplish these aims, we will examine data from 240 subjects over five years: 80 offspring with the risk factor of parental PTSD, 80 offspring without parental PTSD, and 80 demographically comparable subjects (whose parents were not in Europe after 1935). The subjects will be further subdivided so that there are 40 in each group with and without PTSD; half of each subgroup will have a current depressive disorder. Thus, we will recruit a total of 20 subjects in each of 12 subgroups.