PROJECT SUMMARY/ABSTRACTPosttraumatic stress disorder (PTSD) among military Veterans is a critical public health concern. Veteran suiciderates exceed those of the general population with the disorder creating a mental health challenge that is costlyand debilitating. The majority of Veterans with PTSD also have comorbid mental health diagnoses such asgeneralized anxiety disorder substance abuse disorder and major depression. The treatment of Veteran PTSDand comorbid disorders represents an important therapeutic and rehabilitation problem. The disorder is complexand difficult to treat with high treatment dropout and nonresponse rates spurring some Veterans to seekcomplementary integrative health strategies. One promising complementary strategy is the provision of a trainedservice dog. Initial evidence across multiple research groups highlights service dogs as a promising complementto evidence-based practices that can offer short-term improvements. However the long-term effectivenessmechanisms of action and moderators of efficacy remain largely unknown. Thus the overarching objective ofthis proposal is to understand how why and for whom PTSD service dogs are most effective.To address this objective the present project will assess the longitudinal efficacy and dose-response curve ofservice dogs for Veteran PTSD symptomology and psychosocial functioning (Aim 1). To understand how andwhy the intervention works this project will also implement theory-driven quantification of potential mechanismsof action that may mediate service dog efficacy (Aim 2). Finally to understand for whom and under whatcircumstances the intervention works best this project will define moderators of service dog efficacy byexamining the heterogeneity of treatment effects (Aim 3). The research design will consist of a two-armrandomized clinical trial (RCT) with longitudinal assessments at 0 6 and 12 months. Assessments will consistof comprehensive monitoring across six data streams including: (1) blinded clinician assessment of PTSDsymptomology (2) standardized surveys of psychosocial functioning (3) ecological momentary assessment ofdaily emotional experiences and activities (4) salivary biomarkers of two major stress response systems viacortisol and alpha-amylase (5) physical activity and sleep via actigraphy-based wristband monitoring and (6)canine assessments of behavior temperament and physiological co-regulation with the human partner. Resultsare expected to elucidate the clinical impact of service dogs for military Veterans with PTSD as well as thebiobehavioral mechanisms of action and characteristics that moderate efficacy. These outcomes will support thelong-term goal of accelerating complementary and integrative health interventions through optimized andevidence-based service dog interventions. As such this project will further advance the scientific understandingof human-animal interactions for psychosocial health.