Identifying Transdiagnostic Intervention Targets for PTSD-SUD Comorbidity in a Vulnerable Population: A Mixed-Method Study - Project Summary This study aims to identify transdiagnostic mechanisms of posttraumatic stress disorder (PTSD)-substance use disorder (SUD) comorbidity among trauma-exposed transgender and gender diverse (TGD) adults. Significance: TGD populations are virtually absent from PTSD-SUD research despite the alarming and disproportionately high rates of exposure to violence, PTSD, and SUD observed in this population. Existing theory suggests that these disparities are driven by cumulative exposure to stigma associated with having a minoritized gender identity (i.e., gender minority stress). To inform the development of integrated PTSD-SUD interventions for TGD and other minoritized people, research is needed to identify transdiagnostic, culturally-congruent mechanisms of PTSD-SUD risk in the context of chronic exposure to minority stress. Objectives and methods: Chiefly, the proposed study is designed to clarify how population-level PTSD-SUD disparities manifest psychosocially (i.e., via daily behaviors and internal/external experiences) and physiologically (i.e., within the body) to inform the development of evidence-based, integrative PTSD-SUD treatment principles. Leveraging the resources and baseline data of an existing parent study (SC3 GM136580; PI: Berke), I will recruit 70 TGD adults into a two-part study. Following a baseline biopsychosocial assessment (i.e., clinical interview, salivary stress hormone collection, self-report surveys), participants will complete ecological momentary assessment (EMA) for 14 days to assess patterns and predictors of daily co-fluctuation in exposure to gender minority stress (e.g., discrimination), substance use, and PTSD symptoms. This will be achieved by characterizing concurrent and prospective associations of daily co-occurrence among discrimination exposure, substance use, and PTSD symptoms (Aim 1) and identifying transdiagnostic mediators (i.e., internalized stigma, emotion dysregulation; Aim 2) and physical health risk correlates (i.e., chronic disease prevalence, stress hormone reactivity; Aim 3) of these associations. Innovation: This study leverages a novel, unified biopsychosocial framework that accounts for relevant biological (e.g., stress response dysregulation), psychological (e.g., emotion dysregulation), and socio-environmental (e.g., stigma) factors that shape PTSD-SUD risk in this population. Identifying modifiable risk factors that cut across PTSD, SUD, and the conditions of gender minority stress in which they co-occur will directly inform future development of transdiagnostic, integrated PTSD-SUD intervention frameworks for TGD people by yielding rich biopsychosocial data on clinical risk factors for PTSD-SUD comorbidity among TGD people. Findings from the project will also set the stage for research and intervention paradigms that benefit all minoritized subpopulations that are disproportionately impacted by identity-related violence by promoting a shift toward more patient-centered approaches to health equity interventions. Proposal relevant to NOT-MD-19-001.