ANALYSIS OF HIPPOCAMPAL VOLUME IN AGING COMBAT VETERANS WITH PTSD

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们在过去十年的研究描述了创伤后应激障碍(PTSD)患者下丘脑-垂体-肾上腺(HPA)轴的变化。具体地说，在越南退伍军人和患有创伤后应激障碍的大屠杀幸存者中，我们发现地塞米松(DEX)导致基础皮质醇水平降低，皮质醇负反馈抑制增强。然而，越南退伍军人表现出更强的昼夜节律性，而在年长的大屠杀幸存者中，我们观察到皮质醇在昼夜周期中的波动范围较小，类似于正常衰老时动态范围的抑制。因此，这些老年受试者表现出一些典型的与创伤后应激障碍相关的特征(皮质醇降低，对DEX的抑制作用增强)和一些与衰老相关的特征(昼夜节律变平)。本研究旨在探讨老年(50岁)创伤后应激障碍患者各种神经内分泌标志物的年龄相关性变化，并评价这些变化对患者功能的影响。我们将比较战斗暴露和非暴露受试者的症状、基线认知和记忆表现，以及各种生物学指标，包括24小时尿皮质醇、昼夜唾液皮质醇采样以及地塞米松抑制试验(DST)前后的血浆皮质醇和淋巴细胞糖皮质激素受体水平。此外，对于那些符合医学条件并愿意参与的人，我们将比较老年PTSD患者的平面(MRI)和功能(PET)成像数据，以了解HPA改变及其相关(可能是由此而来的)认知损害的解剖和功能相关性。本研究的目的是检测患有和不患有创伤后应激障碍和/或MDD的老年退伍军人的神经内分泌、神经解剖学和认知测量。这项拨款建议检验以下假设，即糖皮质激素受体敏感性的增加是创伤后应激障碍患者海马萎缩和记忆力下降的基础，这样做将为糖皮质激素毒性假说与海马萎缩的关系提供系统和全面的探索。

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. Our research over the last decade has described alterations of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD). Specifically, in both Vietnam combat veterans and Holocaust survivors with PTSD, we have found reduced levels of basal cortisol and enhanced cortisol negative feedback inhibition in response to dexamethasone (DEX). However, Vietnam veterans show increased circadian rhythmicity whereas in elderly Holocaust survivors we have observed a smaller range of cortisol fluctuations over the diurnal cycle, similar to the dampening of the dynamic range seen in normal aging. Thus, these elderly subjects show some features typically associated with PTSD (low cortisol, enhanced suppression to DEX) and some features associated with aging (flattening of circadian rhythm). The current study is conceived to investigate the age associated changes of various neuroendocrine markers of PTSD and to evaluate the functional impact of those changes in aging (¿ age 50) PTSD patients. We will compare combat exposed and non-exposed subjects on symptomatology, baseline cognitive and memory performance, and various biological measures including 24-hour urinary cortisol, circadian salivary cortisol sampling, and plasma cortisol and lymphocyte glucocorticoid receptor levels before and after DEX (dexamethasone suppression test (DST)). In addition, for those medically eligible, and willing to participate, we will compare flat (MRI) and functional (PET) imaging data in aging PTSD patients for areas of interest with respect to the anatomic and functional correlates of HPA alterations and their associated (and perhaps consequent) cognitive impairments. The purpose of this study is to examine neuroendocrine, neuroanatomic, and cognitive measures in aging combat veterans with and without PTSD and/or MDD. This grant proposes to test the hypothesis that increased sensitivity of the glucocorticoid receptor underlies hippocampal atrophy and memory decline in PTSD, and in doing so will provide a systematic and comprehensive exploration of the glucocorticoid toxicity hypothesis in relation to hippocampal atrophy.