Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD

项目总结/摘要 酒精使用障碍（AUD）和创伤后应激障碍（PTSD）经常同时发生，并且与 具有显著的发病率、死亡率和卫生保健支出。退伍军人面临的共同风险增加- 发生AUD和PTSD，患病率比一般人群高2-4倍。我们集团 开发了一种综合干预措施，名为PTSD和物质使用障碍的同时治疗 使用延长暴露（科普）。科普结合了经验验证的认知行为技术 长期暴露（PE）治疗创伤后应激障碍。在退伍军人中进行的几项随机对照试验 和平民证明了科普在显着减轻AUD和PTSD症状方面的功效。尽管 尽管有积极的调查结果，但仍有很大的空间来改善治疗结果和提高保留率。 越来越多的数据表明，神经肽催产素（OT）是一个有前途的候选人，以提高 对合并发生的AUD和PTSD进行心理社会干预，因为OT针对神经生物学和行为学 这两种疾病共同的失调。临床前和临床研究证明OT能够 改善各种与酒精相关的行为（例如，渴望，戒断症状，耐受性，乙醇自我- 管理），增强恐惧消退，并促进与成功相关的亲社会行为。 心理社会治疗结果（例如，信任、社会认知）。在一项随机对照的初步研究中，我们的小组 发现在每周一次的PE治疗之前给予OT是安全的，耐受性良好， 与安慰剂相比，PTSD症状加速减轻。尽管经验和理论 支持加强心理社会干预，如科普与OT是强大的，没有研究迄今已 研究了这种结合的方法。建议的第二阶段研究的主要目的，是研究 与安慰剂相比，OT在减少退伍军人（1）饮酒和（2）PTSD症状方面的疗效 接受科普治疗。为了实现这一目标，我们将采用一个手动的，以证据为基础的，认知行为 干预（科普）;随机、双盲、安慰剂对照研究设计;标准化、重复 在多个时间点的临床结果的依赖措施;我们将利用与 完善的退伍军人事务部诊所准备有效地将积极的发现转化为实践。此外，为了评估 所谓的神经生物学机制的变化，我们将采用功能性磁共振成像（fMRI） 并检查AUD生物标志物。拟议的研究直接涉及以下使命： 国家酒精滥用和酒精中毒研究所（NIAAA），因为它旨在确定药理学 同时治疗共同发生的AUD和PTSD。这项研究的结果将提供新的 信息和机制的见解，以直接通知临床实践，并加快在这个高度研究 研究领域。

PROJECT SUMMARY/ABSTRACT Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co- occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the positive findings, there remains substantial room for improving treatment outcomes and enhancing retention. Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self- administration), enhance fear extinction, and promote prosocial behaviors associated with successful psychosocial treatment outcomes (e.g., trust, social cognition). In a randomized controlled pilot study, our group found that OT administration prior to weekly PE therapy sessions was safe, well-tolerated, and resulted in accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have examined this combined approach. The primary objective of the proposed Stage II study is to examine the efficacy of OT as compared to placebo in reducing (1) alcohol use, and (2) PTSD symptoms among Veterans receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral intervention (COPE); a randomized, double-blind, placebo-controlled study design; standardized, repeated dependent measures of clinical outcomes at multiple time points; and we will leverage close collaboration with well-established VA clinics prepared to efficiently translate positive findings into practice. In addition, to evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment and examine AUD biomarkers. The proposed study directly addresses the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in that it aims to identify pharmacologic treatments to address co-occurring AUD and PTSD simultaneously. The findings from this study will provide new information and mechanistic insights to directly inform clinical practice and accelerate the research in this highly understudied area.