fMRI Predictors of Treatment Response in Posttraumatic Stress Disorder (PTSD)
Condition: Posttraumatic Stress Disorder (PTSD)
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      To employ a fear learning-extinction paradigm with functional magnetic resonance imaging
      (fMRI) and skin conductance response (SCR) assessments among patients with posttraumatic
      stress disorder (PTSD) and trauma exposed healthy controls, aiming to a) clarify neural
      circuits underlying PTSD and b) to probe brain based predictors of symptomatic improvement in
      response to Prolonged Exposure (PE) treatment, and first line treatment for PTSD.
    

Detailed description: 
      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.
    

Intervention name(s): Prolonged Exposure (PE)
Intervention type(s): Behavioral
Intervention description(s): Prolonged Exposure (PE) therapy consists of ten 90-minute sessions. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. The therapist helps the patient cognitively restructure his/her experience of the traumatic event. Each week the narrative is elaborated, becoming more detailed and exhaustive, until the patient habituates to it, extinguishing the anxiety it formerly aroused.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science