Written Exposure Therapy embedded into residential substance use treatment: Efficacy and mechanisms for co-occurring substance use and PTSD - Project Summary/Abstract The overarching goal of this Career Development Award (K23) is to provide Dr. Robyn Ellis with targeted training and research experiences critical to becoming an independent investigator conducting mechanistic clinical trials of substance use and posttraumatic stress disorder (SUD-PTSD) treatment. This application outlines an integrated training and research plan to be carried out at McLean Hospital and Harvard Medical School that will provide Dr. Ellis with the skills needed to achieve her career goals. Under the mentorship of experts in SUD, PTSD, and endocrinology, Dr. Ellis’ training will focus on: (1) clinical trials with SUD-PTSD populations (Drs. McHugh and Hien), (2) advanced statistical analysis for mechanistic clinical trials (Dr. Fitzmaurice), (3) assessment of autonomic activity (Dr. Seligowski), and (4) the influence of sex on SUD and PTSD, including methods to assess sex hormones (Drs. McHugh, Seligowski, and Miller). Dr. Ellis will apply the skills acquired during the training period to conduct a pilot randomized controlled trial (RCT) of a brief treatment for PTSD, Written Exposure Therapy (WET), within residential SUD care among women with SUD- PTSD. Research shows that individuals with SUD-PTSD demonstrate worse clinical outcomes than those with each disorder alone, and women are disproportionately impacted by SUD-PTSD. Although, there are established mechanisms of PTSD treatment, it is unknown if treatment functions similarly among those with SUD-PTSD and there is initial evidence that co-occurring SUD may negatively influence fear learning. Further, low fluctuating estradiol has been shown to impair fear extinction, a putative mechanism of PTSD treatment, however the influence of estradiol on PTSD treatment mechanisms has yet to be tested. To address these gaps, Dr. Ellis will conduct a pilot RCT of WET in residential SUD care compared to neutral writing. Aim 1 will test the efficacy of WET for PTSD and substance use outcomes. Aim 2 will quantify the effects of WET on fear extinction, indexed using trauma-cued autonomic activity (heart rate, skin conductance, heart-rate variability), and trauma-reactive craving. Aim 3 will quantify the influence of endogenous estradiol on changes in treatment mechanisms. The central hypothesis is that women who complete WET will demonstrate greater improvement in PTSD and substance use outcomes, greater fear extinction, and greater reduction in trauma-reactive craving compared to those who complete neutral writing. We also hypothesize that women with higher versus lower estradiol pre-treatment will demonstrate greater fear extinction. This contribution will provide pilot data for an R01 proposal for a large-scale mechanistic trial of WET to test sex differences in mechanisms and outcomes, and ultimately lead to improved long-term SUD-PTSD outcomes through tailored treatment that addresses the unique needs of women with SUD-PTSD.
