GLUCOCORTICOID RESPONSIVITY IN GULF WAR VETERANS

海湾战争退伍军人的糖皮质激素反应

• 批准号: 7380564
• 负责人: RACHEL YEHUDA
• 金额: $ 0.75万
• 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/7380564
• 关键词: brain; cortisol; glucocorticoids; health; memory; metabolism; short term memory; stress; veterans; war /peace

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.

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，不一定是研究者所在机构。这项拟议中的研究旨在确定是否会增加对应激激素的敏感性（即，海湾战争退伍军人（GWVs）大脑中的糖皮质激素），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。这将通过检查氢化可的松对GWV伴或不伴PTSD和未参加海湾战争的退伍军人伴或不伴PTSD的记忆表现和大脑葡萄糖摄取的影响进行评估，这些影响通过正电子发射断层扫描（PET）神经成像技术测量。基于我们以前的观察增强皮质醇负反馈抑制，这已经使用外周神经内分泌技术进行了评估，我们假设，将有更大的敏感性氢化可的松在GWVs，这种增加将反映在工作记忆障碍和海马代谢的变化后氢化可的松的挑战。低皮质醇和增强的负皮质醇抑制的观察最近在我们的实验室被扩展到海湾战争的退伍军人。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测量的改变是否与PTSD和/或健康症状（包括记忆症状）有关。这项研究是特别必要的，因为记忆障碍和神经精神症状是症状性GWVs的主要投诉之一。在一定程度上，这些投诉是压力相关的，这项研究将允许检查压力，记忆和其他症状之间的关系，神经内分泌和大脑的变化，可能介导他们。 假设： 基于我们以前的观察增强皮质醇负反馈抑制，这已被评估使用外周神经内分泌techniques，我们假设，将有更大的敏感性氢化可的松在GWVs，这种增加将反映在工作记忆障碍和海马代谢的变化后氢化可的松的挑战。