fMRI Predictors of Treatment Response in Posttraumatic Stress Disorder (PTSD)

Posttraumatic stress disorder (PTSD) is highly prevalent and debilitating disorder. It is defined by a fearful response to traumatic events, and its clinical picture includes reexperiencing, arousal, and avoidance to reminders of the exposure. Despite efforts to characterize the pathophysiology of PTSD, no biomarkers have been established that aid in diagnosis, treatment development, or prediction of treatment response. Several lines of evidence suggest that PTSD symptoms are mediated by dysfunctional processes involving the brain's fear-circuitry network in general, and extinction learning and recall deficits in particular. Based on our preliminary work in applying fear extinction task to healthy humans and patients with PTSD the goal of this renewal RO1 application is to employ an established extinction paradigm with functional magnetic resonance imaging (fMRI) and Skin Conductance Response (SCR) assessments in a large and well characterized sample with PTSD and trauma exposed healthy control (TE-HC) subjects. We plan to clarify circuits underlying PTSD psychopathology and to probe, for the first time, neural circuitry of symptomatic improvement in response to Prolonged Exposure (PE) treatment. This goal is congruent with NIMH strategic plan strategy 1.3 ("identify and integrate biological markers and behavioral indicators associated with mental disorders"). One hundred subjects including 60 individuals with a principal diagnosis of PTSD and 40 trauma exposed healthy controls will be assessed by fMRI and SCR to determine the neural circuitry activation to the fear extinction task. fMRI data will be acquired simultaneously with fear extinction and recall measurement quantified by SCR. All 60 PTSD subjects and 20 randomly assigned TE-HCs subjects will repeat these procedures 10 weeks later, after PTSD subjects have completed 10 weeks of intensive PE treatment. Three months after treatment completion clinical ratings of PTSD severity will be conducted to permit analysis of neural predictors of long term treatment durability. The aims above will be accomplished through four years of study, conducted by a multi-disciplinary research team, comprised of research scientists from Columbia, Harvard and New York Universities, who have conducted studies in PTSD and structural and functional brain imaging. If successful, the study will produce highly needed information on the neural circuitry which underlies deficient extinction and recall in PTSD, and will provide highly important information about the neural effects of Prolonged Exposure treatment, a first line treatment for PTSD. Together these lines of expected findings will not only advance identification of biomarkers associated with PTSD, but also facilitate identification of biomarkers for clinical reponse to an empirically supported treatment.