[CAN POST-TRAUMATIC STRESS DISORDER BE PREVENTED WITH GLUCOCORTICOIDS?]

INTRODUCTION: Glucocorticoids (GCs) play a major role in orchestrating the complex physiological and behavioral reactions essential for the maintenance of homeostasis. These compounds enable the organism to prepare for, respond to and cope with the acute demands of physical and emotional stressors. The appropriate GC release, commensurate with stressor severity, enables the body to properly contain stress responses so as to promote recovery by rapidly restoring homeostasis. Indeed, inadequate GC release following stress not only delays recovery by disrupting biological homeostasis in the short run but can also interfere with the processing or interpretation of stressful information that results in long-term disruptions in memory integration. While conventional wisdom holds that people who develop post-traumatic stress disorder (PTSD) following exposure to extreme trauma might have sustained elevations in GCs, several studies have reported that lower cortisol levels in the acute aftermath of trauma are predictors for subsequent PTSD symptoms. Therefore, it is possible that the administration of exogenous cortisol immediately after exposure to a trauma might alter the trajectory of trauma exposure by promoting recovery. Our group has initiated a series of studies examining the role of GCs in susceptibility to "PTSD-like behaviors" in a well-validated animal model for PTSD. The results of these studies highlight the importance of an initial bolus of endogenous corticosteroids in the normative response to stress as a key to a return to homeostasis. Aberrations in the normative response play an equally pivotal role in determining long-term cyto-architecture, and also localized brain biomolecular and overall neuro-hormonal disruptions underlying the PTSD-like behavioral responses in animals, and may be related to the emotional and behavioral symptoms of PTSD in patients. The data provides initial evidence that a single dose of hydrocortisone administered in the acute aftermath of trauma promotes recovery while promoting enhanced synaptic plasticity and connectivity in the secondary prevention of PTSD. We suggested that exogenous hydrocortisone, if given during the 'window of opportunity' - right after the exposure and before consolidation of the traumatic memory - may promote the restoration of homeostasis by constraining central nervous system activity.