GLUCOCORTICOID RESPONSIVITY IN GULF WAR VETERANS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。拟议的研究旨在确定海湾战争退伍军人（GWVs）的大脑中是否存在与健康症状、部署压力和健康结果（包括海湾战争病（GWI）和/或创伤后应激障碍（PTSD））相关的压力激素（即糖皮质激素）的敏感性增加。这将通过检查氢化可的松对记忆表现和大脑葡萄糖摄取的影响进行评估，这些影响是通过正电子发射断层扫描（PET）神经成像技术在患有和不患有创伤后应激障碍的GWV和没有参加海湾战争的退伍军人中测量的。基于我们之前对皮质醇负反馈抑制增强的观察，我们已经使用周围神经内分泌技术进行了评估，我们假设gwv对氢化可的松的敏感性更高，这种增加将反映在氢化可的松刺激后工作记忆损伤的加剧和海马代谢的变化上。低皮质醇和增强负皮质醇抑制的观察最近在我们的实验室扩展到海湾战争退伍军人。这项工作的潜在意义在于：1)将外周神经内分泌改变与脑功能联系起来；2)同时检查皮质醇对海马代谢和工作记忆表现的影响；3)确定脑功能或外周神经内分泌的改变是否与PTSD和/或健康症状（包括记忆症状）有关。这项研究特别有必要，因为记忆障碍和神经精神症状是症状性gwv的主要主诉。在某种程度上，这些抱怨与压力有关，这项研究将允许检查压力，记忆和其他症状以及可能调节它们的神经内分泌和大脑变化之间的关系。假设：基于我们之前对皮质醇负反馈抑制增强的观察，我们已经使用外周神经内分泌技术进行了评估，我们假设gwv对氢化可的松的敏感性更高，这种增加将反映在氢化可的松刺激后工作记忆损伤的加剧和海马代谢的变化上。

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. The proposed research is designed to determine whether there is increased sensitvity to stress hormones (i.e., glucocorticoids) in the brains of Gulf War Veterans (GWVs), related to health symptoms, deployment stress, and health outcomes including Gulf War Illness (GWI) and/or posttraumatic stress disorder (PTSD). This will be assessed by examining the effect of hydrocortisone on both memory performance and glucose uptake in the brain as measured by Positron Emission Tomography (PET) neuroimaging techniques in GWV with and without PTSD and combat veterans who did not served in the Gulf War with and without PTSD. Based on our previous observations of enhanced cortisol negative feedback inhibition, which has been assessed using peripheral neuroendocrine techniques, we hypothesize that there will be greater sensitivity to hydrocortisone in GWVs and that this increase will be reflected in heightened working memory impairment and changes in hippocampal metabolism following hydrocortisone challenge. The observations of both low cortisol and enhanced negative cortisol inhibition have recently been extended to Gulf War veterans in our laboratory. The potential significance of the proposed work lies in 1) linking peripheral neuroendocrine alterations to brain function, 2) simultaneously examining the effects of cortisol on hippocampal metabolism and working memory performance and 3) identifying whether alterations in the brain function or peripheral neuroendocrine measures are related to PTSD and or health symptoms, including memory symptoms. This research is particularly warranted because memory impairments and neuropsychiatric symptoms are among the chief complaints in symptomatic GWVs. To the extent that these complaints are stress-related, this study will allow examination of the relationships among stress, memory and other symptoms and the neuroendocrine and brain changes that may mediate them. Hypothesis: Based on our previous observations of enhanced cortisol negative feedback inhibition, which has been assessed using peripheral neuroendocrine technigues, we hypothesize that there will be greater sensitivity to hydrocortisone in GWVs and that this increase will be reflected in heightened working memory impairment and changes in hippocampal metabolism following hydrocortisone challenge.