PROSPECTIVE NEUROBIOLOGICAL STUDY OF PTSD

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The major objectives of this competing continuation proposal are: a.)to obtain for the first time sequential measures of hypothalamic-pituitary- adrenal (HPA) axis and sympathetic nervous system (SNS) activity in a large sample of psychologically traumatized persons in the immediate aftermath of the traumatic event and in follow-up; b.) to evaluate the time course of HPA and SNS response patterns in relationship to the development of post-traumatic stress disorder (PTSD); and c.) to examine possible interactions between the SNS and HPA axis in PTSD s pathogenesis. HPA and SNS measures will be obtained in 300 patients shortly after their presentation to the emergency room (ER) of a major urban teaching hospital in Israel following an acute, psychologically traumatic event, and at specified intervals during the next four months. HPA measures will include a.) cortisol, adrenocorticotropin (ACTH), and lymphocyte glucocorticoid receptor (GR) levels measured in saliva, blood, and/or urine; b.) salivary cortisol peak-trough difference, area under the curve, and rate of decline over the diurnal cycle; and c.) percentage of cortisol and GR suppression induced by a 0.5 mg dose of the synthetic steroid dexamethasone. SNS measures will include: a.) heart rate and blood pressure; and b.) norepinephrine, epinephrine, and 3-methoxy-4- hydroxy-phenylglycol (MHPG) levels measured in saliva, blood, and/or urine. Logistic regression will be used to predict PTSD vs. non-PTSD status at four months. Predictor variables will be entered stepwise into the analysis on a chronological basis, e.g., i.) past trauma history; ii.) index traumatic event severity, iii.) response intensity to the index traumatic event; iv.) ER HPA and SNS measures and their interactions; and v.) post-ER HPA and SNS measures and their interactions. In this way, evaluation of HPA and SNS predictor effects and interactions will be adjusted for the effects of other relevant, antecedent variables, and for earlier HPA axis and SNS effects and interactions.