Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) are common consequences of exposure to traumatic events. Despite growing evidence of neurobiological dysfunction in ASD and PTSD, the pathogenesis of these disorders is still unknown. Drs. Osuch and Ursano (Uniformed Services University of the Health Sciences) have received support to conduct a 14-week study that will investigate the efficacy of the serotonergic medication sertraline (Zoloft) in the treatment and prevention of posttraumatic psychiatric sequelae in ASD victims. The present project is an amendment to Drs. Osuch and Ursano's study. It will attempt to identify early psychological and neurobiological abnormalities in ASD. More specifically, the present project will examine to what extent sensitization and conditioning processes, as well as emotional dysregulation, contribute to ASD. We also propose to investigate the potential association between cerebellum dysfunction and peritraumatic dissociations. To accomplish this goal, a series of three experiments will be implemented to investigate: 1) the symptom of exaggerated startle; 2) emotional reactivity to trauma-related and trauma-unrelated cues; and 3) cerebellum functioning using eyeblink conditioning. This study will inform on the short-term consequences of trauma, will help identify potential psychophysiological markers of ASD that emerge following trauma, and will examine the effects of an SSRI on preventing trauma-related neurobiological deficits.

We specifically propose to:

1. Characterize psychophysiological responses in ASD victims shortly after trauma;
2. Assess the effect of sertraline treatment on these psychophysiological responses.

To accomplish aim 1, non-treated ASD victims will be compared to two control groups, a non-ASD trauma group and a non-trauma healthy group. The two control groups will be used to disentangle the effect of trauma from the effect of acute stress disorder. To accomplish aim 2, the ASD sertraline group will be compared to the ASD placebo group following treatment.

Forty victims of serious motor vehicle collision (MVC) with ASD will be recruited from a community hospital emergency room and evaluated with clinical assessments, and standardized questionnaires within 2 weeks after the MVC. The subjects will then be randomized to either sertraline or placebo for 8 weeks duration. Psychometric testing and psychological evaluations will be conducted at 4, 10 weeks post-MVC, and after a 2-week taper of the medication and 2 more weeks (14 weeks post-MVC).

We hypothesize that ASD patients will show:

An enhancement or sensitization of baseline startle;

An increase in autonomic arousal and in startle amplitude to trauma-related cues;

A delayed eyeblink conditioning;

Normalization of these deficits after sertraline treatment.

This preliminary study is expected to lay the groundwork for a larger study of the early impact of traumatic events on psychophysiological and psychological processes. In the long-term, we expect to 1) better characterize the onset of symptoms and their evolution over time following trauma, 2) identify psychophysiological markers for PTSD, 3) identify ASD victims at-risk for PTSD, and 4) improve our ability to prevent the development of chronic psychopathology following trauma.