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

患有创伤后应激障碍(PTSD)的退伍军人经常有严重的酒精问题，许多 在我们最好的治疗下继续受苦。虽然长期暴露(PE)是一线治疗方法， 靶向辅助药物治疗可能使同时患有酒精使用障碍和创伤后应激障碍的人受益 (澳元/创伤后应激障碍)事实上，最近的证据表明，托吡酯(TOP)可能是治疗并存疾病的唯一有效药物 AUD/PTSD患者。TOP可能通过对抗AUD和PTSD的共病来改善治疗 作为每种障碍的一部分而发生的神经适应过程。然而，尽管有令人兴奋的新证据表明 TOP可能会加强对AUD/PTSD的心理治疗，目前还没有工作来了解如何 TOP可能影响AUD/PTSD相关神经回路。鉴于PE和TOP的前景光明的组合，最近 资助的随机对照试验(RCT)将检验它们在治疗慢性阻塞性肺疾病中的联合疗效。 患有澳元/创伤后应激障碍的退伍军人。以确定这种新的治疗组合的作用机制，以及 TOP对这一动态的具体贡献，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AUD/PTSD的临床相关神经标记物，预测 课程和定义缓解期。 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周的两次治疗中的一次 作为已经资助的随机对照试验的一部分，比较PE加安慰剂的相对有效性 (PE+解放军)，对PE+TOP(PE+TOP)。我们的中心假设是PE会改善神经调节 前额叶皮质对情绪反应中心的作用，TOP的加入将增强 图片反应范式中PE对威胁和渴求相关激活的影响。我们的主要目标是 (1)确定网络中大脑反应的基线模式是否从属于恐惧处理或酒精 线索反应性预测不同处理间的AUD/PTSD反应，以及(2)比较每种处理的效果 被认为是维持AUD和PTSD的神经子过程。 拟议的转译神经成像研究有可能阐明 循证治疗可以改善高度流行的和 高度受损的退伍军人群体。将临床相关的神经模式与心理治疗成果联系起来 可以提高我们对患有这种严重并发症的退伍军人进行有效分诊和治疗的能力。因此， 这项研究的基本原理是改善证据基础，以告知AUD患者和 创伤后应激障碍可以从这两种疾病中获得持续的康复。 TOP的效果还没有在AUD、PTSD或AUD/PTSD样本中使用功能磁共振进行评估，更不用说 退伍军人。本申请试图阐明治疗可通过其驱动恢复的机制， 对于那些最有可能康复的人来说，通过整合最先进的神经成像和基于证据的 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.