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 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. 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.