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

患有创伤后应激障碍（PTSD）的退伍军人通常有严重的酗酒问题，许多人 在接受我们最好的治疗后继续受苦虽然长期暴露（PE）是一线治疗， 有针对性的连续药物治疗可能对那些同时患有酒精使用障碍和创伤后应激障碍的人有益， (AUD/PTSD）。事实上，最近的证据表明，托吡酯（TOP）可能是唯一有效的共病 AUD/PTSD患者。TOP可能通过抵消AUD和PTSD的共病而改善治疗 神经适应过程是每种疾病的一部分。然而，尽管有令人兴奋的新证据表明， TOP可能会增强AUD/PTSD的心理治疗，但还没有工作来了解如何做到这一点。 TOP可能影响AUD/PTSD相关神经回路。鉴于PE和TOP的组合前景看好，最近， 资助的随机对照试验（RCT）将检查它们在治疗 患有AUD/PTSD的退伍军人。确定这种新型治疗组合的作用机制， TOP对这种动态的具体贡献，我们建议使用功能磁共振成像 （功能磁共振成像），在这项随机对照试验的背景下，检查临床相关的神经标志物的AUD/PTSD，预测 并定义缓解。 参与者将是88名患有AUD和PTSD的退伍军人，他们将接受为期16周的两次治疗之一。 作为已经资助的RCT的一部分，比较PE+安慰剂的相对有效性 (PE+ PLA），对抗PE + TOP（PE + TOP）。我们的中心假设是，PE将改善神经调节， 前额叶皮层在情绪反应中心的功能，而TOP的加入将增强 在图形反应范式中，PE对威胁和渴望相关激活的影响。我们的主要目标是 (1)以确定是否基线模式的大脑反应在网络subserving恐惧处理或酒精 提示反应性预测治疗间的AUD/PTSD反应，以及（2）比较每种治疗的效果 被认为是维持AUD和PTSD的神经子过程。 拟议的翻译神经影像学研究有可能阐明的过程， 基于证据的治疗可以改善高度流行的功能和心理恢复， 高度受损的退伍军人群体。将临床相关神经模式与心理治疗收益联系起来 可以提高我们的能力，有效地分流和治疗退伍军人与这种严重的合并症。因此 这项研究的基本原理是改善证据基础，告知AUD患者如何 PTSD可以从这两种疾病中获得持续的恢复。 TOP的影响尚未在AUD、PTSD或AUD/PTSD样本中使用fMRI进行评估，更不用说 老兵本申请试图阐明治疗可以驱动恢复的机制， 通过整合最先进的神经影像学和循证医学， 治疗。

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.