Developing and Evaluating a Positive Valence Treatment for Alcohol Use Disorder with Anxiety or Depression

项目摘要 只有20-30%的酒精使用障碍（AUD）患者表现出长期的益处， 药理学（例如，阿坎酸，纳曲酮）和行为疗法（例如，认知行为疗法， 应急管理）。近一半寻求AUD治疗的人在临床上 显著的焦虑和抑郁症状（ANX/DEP），这与更差的长期结果有关。积极 价系统（PVS）功能障碍是AUD和ANX/DEP的常见和有害特征， 预测不良功能和预后。虽然PVS功能障碍代表了一种共同的病理生理学 在AUD和ANX/DEP中，它不是现有治疗的充分靶向机制。 我们的团队开发了一种行为干预，积极性放大（AMP），以提高PVS 通过增加对非药物奖励的暴露和反应来发挥作用。在我们以前的工作中，AMP是 发现增加正效价结果（例如，积极影响，社会联系，生活满意度）， 增强PVS神经回路的反应性（即，纹状体对社会奖励的反应），并减少负 ANX/DEP个体的效价结果和症状。我们已经开始修改这一干预措施， 治疗合并发生的AUD和ANX/DEP（AMP-A），完成初步试点可行性研究。 在建议的研究中，我们会根据定性和 从临床医生和参与者的定量反馈，并完成了一项试点研究的协议，8 诊断为AUD并报告临床ANX/DEP症状升高的个体-进一步完善 根据该飞行员的反馈制定的协议。然后，我们将招募60名AUD+ANX/DEP的个人， 将他们随机分配至完成AMP-A或认知行为疗法（CBT）-AUD的一线治疗， 对PVS影响不大。所有参与者将在研究开始前、研究期间和研究结束后完成临床和自我报告测量。 治疗后和3个月随访时。 本项目将实现以下目标：（1）进一步开发和完善AMP-A，以优化其 可接受性和潜在的临床效用;（2）确定AMP-A与CBT相比对PVS的影响， 通过积极情感、社会联系、幸福感和奖励处理的自我报告来衡量;（3） 确定PVS功能的增加是否与酒精使用的更大临床改善相关， 焦虑和抑郁结果将对治疗AUD和并发症具有重要意义。 通过确定直接针对PVS的效用来确定焦虑或抑郁，这将为未来铺平道路。 寻求补救这些条件的有害影响的研究。

PROJECT SUMMARY Only 20-30% of individuals with alcohol use disorder (AUD) exhibit long-term benefits with leading pharmacologic (e.g., acamprosate, naltrexone) and behavioral therapies (e.g., cognitive behavioral therapy, contingency management). Nearly half of individuals seeking treatment for AUD experience clinically significant anxiety and depression symptoms (ANX/DEP), which relate to worse long-term outcomes. Positive valence system (PVS) dysfunction is a common and pernicious feature of both AUD and ANX/DEP that is predictive of poor functioning and prognosis. Although PVS dysfunction represents a shared pathophysiologic mechanism across AUD and ANX/DEP, it is not sufficiently targeted by existing treatments. Our team developed a behavioral intervention, Amplification of Positivity (AMP), to enhance PVS function through increasing exposure and responsivity to non-drug rewards. In our previous work, AMP was found to increase positive valence outcomes (e.g., positive affect, social connectedness, life satisfaction), enhance reactivity of PVS neural circuits (i.e., striatal response to social reward), and decrease negative valence outcomes and symptoms for individuals with ANX/DEP. We have begun to modify this intervention for the treatment of co-occurring AUD and ANX/DEP (AMP-A), completing an initial pilot feasibility study. For the proposed study, we will further develop and refine AMP-A based upon qualitative and quantitative feedback from clinicians and participants and complete a pilot study of the protocol with eight individuals diagnosed with AUD and reporting clinically elevated ANX/DEP symptoms - further refining the protocol based on feedback from this pilot. We will then recruit 60 individuals with AUD+ANX/DEP and randomize them to complete AMP-A or cognitive behavioral therapy (CBT) – a first-line treatment for AUD that has small effects on the PVS. All participants will complete clinical and self-report measures before, during and after therapy and at 3-month follow-up. This project will accomplish the following aims: (1) Further develop and refine AMP-A to optimize its acceptability and potential clinical utility; (2) Determine the effects of AMP-A compared to CBT on the PVS, as measured by self-report of positive affect, social connectedness, well-being, and reward processing; (3) Determine whether increases in PVS function are associated with greater clinical improvement of alcohol use, anxiety, and depression. Results will have important implications for the treatment of AUD and co-occurring anxiety or depression by determining the utility of directly targeting the PVS, which will pave the way for future research seeking to remediate the harmful effects of these conditions.