Neuromarkers of Treatment for Comorbid Posttraumatic Stress Disorder and Alcohol Use Disorder

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Veterans with posttraumatic stress disorder (PTSD) often have serious problems with alcohol, and many continue to suffer following our best treatments. While Prolonged Exposure (PE) is a first-line treatment, targeted adjunctive pharmacotherapy may benefit those with both an alcohol use disorder and PTSD (AUD/PTSD). In fact, recent evidence suggests that topiramate (TOP) may be uniquely effective for comorbid AUD/PTSD patients. TOP may improve treatment for the comorbidity of AUD and PTSD by counteracting neuroadaptive processes that occur as part of each disorder. However, despite exciting new evidence that TOP may enhance psychotherapeutic treatment for AUD/PTSD, no work has been done to understand how TOP may affect AUD/PTSD relevant neurocircuits. Given the promising combination of PE and TOP, a recently funded randomized controlled trial (RCT) will examine their combined effectiveness in the treatment of Veterans with AUD/PTSD. To identify the mechanisms of action of this novel combination of treatments, and the specific contribution of TOP to this dynamic, we propose to use functional magnetic resonance imaging (fMRI), in the context of this RCT, to examine clinically relevant neural markers of AUD/PTSD that predict course and define remission. Participants will be 88 Veterans with AUD and PTSD who will receive one of two 16-week long treatment conditions as part of an already funded RCT comparing the relative effectiveness of PE plus placebo (PE+PLA), against PE plus TOP (PE+TOP). Our central hypothesis is that PE will improve neuromodulatory function of the prefrontal cortex over emotional reactivity centers, and that the addition of TOP will enhance PE’s effects on threat- and craving-related activation during pictorial reactivity paradigms. Our primary aims are (1) to determine whether baseline patterns of brain response in networks subserving fear processing or alcohol cue reactivity predict AUD/PTSD response across treatments, and (2) to compare the effect of each treatment on the neural subprocesses thought to maintain AUD and PTSD. The proposed translational neuroimaging study has the potential to elucidate the processes by which evidence based treatments may improve functional and psychological recovery for a highly prevalent and highly impaired population of Veterans. Linking clinically relevant neural patterns to psychotherapeutic gains can improve our ability to effectively triage and treat Veterans with this crippling comorbidity. Therefore, the fundamental rationale for this study is to improve the evidence base that informs how patients with AUD and PTSD can attain sustained recovery from both of these disorders. The effects of TOP have not been evaluated using fMRI in an AUD, PTSD, or AUD/PTSD sample, let alone Veterans. This application seeks to elucidate the mechanisms through which treatments may drive recovery, and for whom recovery is most likely, via the integration of state-of-art-neuroimaging and evidence based treatments.