DESCRIPTION (provided by applicant): 1 Nearly 2.5 million troops have served in Iraq and Afghanistan . As of November 2013, over 287,000 members of this cohort were diagnosed with posttraumatic stress disorder (PTSD), costing the VA $68 million in outpatient PTSD treatment and $1.94 billion in overall care2.While there are several validated treatment options for PTSD, little objective guidance exists for selecting the best treatment option for a given patient. Based on current knowledge, physiological response patterns to trauma-related imagery are a promising potential measure to fill this gap. Research has consistently shown that PTSD is associated with heightened physiological reactivity to idiographic trauma-related cues3. Although most individuals with PTSD demonstrate heightened reactivity, a substantial minority do not. Upwards of 40% of individuals with PTSD exhibit non-elevated physiological reactivity to cues when tested in the laboratory3-6, despite their reporting the same levels of subjective arousal as physiological responders. Also, those with dissociative subtype of PTSD have been shown to exhibit attenuated reactivity to trauma-related cue5-6. Given their lack of reactivity to trauma-related stimuli, Veterans who are physiologically non-reactive may be less likely to respond favorably to prolonged exposure (PE) therapy7, the leading evidence-based treatment for PTSD. In such cases, the use of other evidence-based treatments may be indicated8 (e.g., CPT). However, this premise has not yet been tested. Our long-term goal is to personalize treatment, improve clinical outcome, and ultimately improve the lives of Veterans with PTSD. As a first step towards this long term goal, the primary objective of the current proposal is to determine whether physiological non-reactors benefit from PE therapy to the same extent as Veteran reactors. Change in PTSD symptom severity (CAPS-5 total score) will serve as the primary outcome measure. PTSD remission (CAPS-5 diagnostic criteria no longer met) will serve as a secondary outcome measure. Based on findings from our work, as well as evidence from the current literature, we hypothesize that non-reactive, compared to reactive, pretreatment physiological response patterns will predict treatment outcome. Primary Aim: To determine the relationship between pre-treatment physiological reactivity to trauma-related cues and PE treatment outcome. H1: Compared to Veteran reactors, non- reactors will demonstrate a smaller change in PTSD symptom severity scores following PE therapy, after adjusting for comorbidities. H2: Compared to Veteran reactors, non-reactors will have a lower rate of PTSD remission following PE therapy, after adjusting for comorbidities. Exploratory Aim: To determine the relationship between dissociative symptoms, pre- treatment physiological patterns and PE treatment outcome. Q1: Do physiologic reactors and non- reactors differ in the level of reported current dissociative symptoms?...