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

共病创伤后应激障碍和酒精使用障碍治疗的神经标志物

• 批准号: 10038796
• 负责人: ANDREA SPADONI TOWNSEND
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10038796
• 关键词: Affect; Alcohol consumption; Alcoholism; Alcohols; Amygdaloid structure; Anterior; Brain; Corpus striatum structure; Cues; Disease; Disease remission; Dopamine; Effectiveness; Emotional; Ethanol; Evidence based treatment; Exposure to; FDA approved; Fright; Functional Magnetic Resonance Imaging; Funding; Glutamates; Human; Impairment; Individual; Link; Motivation; Participant; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Psychotherapy; Randomized Controlled Trials; Recovery; Relapse; Rest; Risk Factors; Sampling; Severities; Symptoms; Triage; Veterans; Work; alcohol cue; alcohol effect; alcohol response; alcohol use disorder; base; blood oxygenation level dependent response; clinically relevant; comorbidity; craving; cue reactivity; drinking; dual diagnosis; effective therapy; evidence base; improved; military veteran; neural network; neural patterning; neuroimaging; neuroregulation; neurotransmission; novel; psychologic; psychosocial; relating to nervous system; relative effectiveness; response; targeted treatment; topiramate; treatment effect; treatment response; trial comparing

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.

具有创伤后应激障碍（PTSD）的退伍军人通常在酒精方面存在严重问题，许多人 继续遵循我们的最佳治疗方法。虽然长时间的暴露（PE）是一线治疗 有针对性的辅助药物疗法可能使酒精使用障碍和PTSD的患者受益 （AUD/PTSD）。实际上，最近的证据表明，Topramate（顶部）可能对合并症具有独特的有效性 AUD/PTSD患者。顶部可以通过抵消来改善AUD和PTSD合并症的治疗方法 作为每种疾病的一部分发生的神经适应过程。但是，渴望令人兴奋的新证据 TOP可能会增强AUD/PTSD的心理治疗治疗，没有做任何工作来了解如何 顶部可能会影响AUD/PTSD相关的神经电路。考虑到PE和TOP的承诺组合，最近 资助的随机对照试验（RCT）将检查其在治疗中的综合有效性 具有AUD/PTSD的退伍军人。确定这种新型治疗组合的作用机理，以及 顶部对这种动态的特定贡献，我们建议使用功能磁共振成像 （fMRI）在此RCT的背景下，检查AUD/PTSD的临床相关神经标志物 课程并定义缓解。 参与者将是88名退伍军人，有AUD和PTSD，他们将获得两个16周的治疗之一 条件作为已经资助的RCT的一部分，比较了PE Plus安慰剂的相对有效性 （PE+PLA），对PE Plus Top（PE+TOP）。我们的中心假设是PE将改善神经调节性 前额叶皮层在情绪反应性中心的功能，并且顶部的添加将增强 PE对图形反应性范式中与威胁和渴望相关的激活的影响。我们的主要目的是 （1）确定网络中大脑反应的基线模式是否在恐惧加工或酒精 提示反应性预测跨处理的AUD/PTSD反应，（2）比较每种处理的效果 在被认为维护AUD和PTSD的神经子过程中。 拟议的翻译神经影像学研究有可能阐明该过程 基于证据的治疗可能会改善高度普遍的功能和心理恢复 退伍军人的高度受损。将临床上相关的神经元模式与心理治疗的增长联系起来 可以通过这种剪裁合并症来提高我们有效分类和治疗退伍军人的能力。因此， 这项研究的基本理由是提高证据基础，以告知AUD和AUD患者的方式 PTSD可以从这两种疾病中持续恢复。 在AUD，PTSD或AUD/PTSD样本中，尚未使用fMRI评估TOP的效果，更不用说 退伍军人。该应用程序旨在阐明治疗可能导致恢复的机制， 并且最有可能恢复的人，通过整合前面的神经成像和基于证据的 治疗。