CEREBRAL 18FDG UPTAKE FOLLOWING HYDROCORTISONE IN PTSD

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DESCRIPTION (Adapted from Applicant's Abstract): Dr. Robert Grossman received his M.D. from the Mount Sinai School of Medicine, was a resident at Cornell New York Hospital-Westchester Division, completed an NIMH sponsored research fellowship in the neurobiology of trauma and personality, and has been an Assistant Professor of Psychiatry since July, 1996. Over the past 4 years he has been engaged in research of glucocorticoid and serotonin function in post traumatic stress disorder (PTSD) and borderline personality disorder with his mentors Rachel Yehuda, Ph.D. and Larry Siever, M.D. He has recently begun preliminary work in quantitative hippocampal neuroimaging in trauma-related disorders with Monte Buchsbaum M.D. Dr. Grossman's immediate career goals are to devote at least 75% of his time over the next five years to further conceptual and technical training in eruoendocrinology, structural, functional, and metabolic neuroimaging, and neuropsychological assessment of cognitive function. His intensive training program will include: 1) formal postgraduate coursework; 2) supervision and interaction with mentors, collaborators and scientific advisors; and 3) conduct of original research. Dr. Grossman's long-term career goals are to establish himself as an independent investigator within an academic psychiatry program in the area of central glucocorticoid-mediated effects on hippocampal volume and functioning. Two major findings in the field of PTSD research have been hypothalamic-pituitary-adrenal (HPA) axis alterations and smaller hippocampal volumes. Preclinical studies suggest that central glucocorticoid-mediated effects may be associated with these hippocampal abnormalities. In addition, the hippocampus is an important region (both structural and functionally) intimately involved in declarative memory. Dr. Grossman's broad aims are to investigate these relationships in PTSD. Dr. Grossmans's specific aims are to measure and correlates: 1) central glucocorticoid sensitivity utilizing a placebo-controlled hydrocortisone challenge followed by 18-FDG uptake and PET scanning; 2) peripheral HPA axis measures of cortisol negative feedback sensitivity to dexamethasone and plasma lymphocyte glucocorticoid receptors; 3) hippocampal volume using MRI; 4) neuropsychological deficits at baseline; and 5) alternations in declarative memory function following a hydrocortisone/placebo challenge. Subject groups will include PTSD subjects, traumatized subjects without PTSD, and health nontraumatized subjects. Animal studies have found flucocorticoid-mediated effects to include both hippocampal cell atrophy and death. These models have also demonstrated that particular interactions can prevent or reverse hippocampal atrophy. The results of these studies will likely have broad and important implications for the neuroscience's, and treatment implications in PTSD patients and perhaps other populations with HPA axis alterations and hippocampal findings such as Suching's disease, Alzheimer's disorder, and recurrent major depression.