ANALYSIS OF HIPPOCAMPAL VOLUME IN AGING COMBAT VETERANS WITH PTSD

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。在过去的十年中，我们的研究描述了创伤后应激障碍（PTSD）下丘脑-垂体-肾上腺（HPA）轴的改变。具体来说，在越南战斗退伍军人和大屠杀幸存者与创伤后应激障碍，我们已经发现降低水平的基础皮质醇和增强皮质醇负反馈抑制反应地塞米松（DEX）。然而，越战老兵的昼夜节律增加，而在老年大屠杀幸存者中，我们观察到昼夜周期内皮质醇波动范围较小，类似于正常衰老中动态范围的抑制。因此，这些老年受试者显示出一些通常与PTSD相关的特征（低皮质醇，增强的对DEX的抑制）和一些与衰老相关的特征（昼夜节律的平坦化）。目前的研究旨在调查与年龄相关的各种PTSD神经内分泌标志物的变化，并评估这些变化对老年（50岁）PTSD患者的功能影响。我们将比较战斗暴露和非暴露受试者的行为学，基线认知和记忆能力，以及各种生物学指标，包括24小时尿皮质醇，昼夜节律唾液皮质醇采样，血浆皮质醇和淋巴细胞糖皮质激素受体水平之前和之后DEX（地塞米松抑制试验（DST））。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（可能是随之而来的）认知障碍的解剖和功能相关性。 本研究的目的是检查神经内分泌，神经解剖学，和认知的措施，在老年退伍军人与创伤后应激障碍和/或抑郁症。这项资助旨在检验糖皮质激素受体敏感性增加是PTSD海马萎缩和记忆力下降的基础这一假设，并在此过程中对与海马萎缩相关的糖皮质激素毒性假说进行系统和全面的探索。

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.