Reward Sensitivity as a Mechanism of Positive Affect Treatment for Anhedonia

奖励敏感性作为快感缺失积极情感治疗的机制

基本信息

批准号：
10414868
负责人：
MICHELLE G CRASKE
金额：
$ 80.71万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10414868
关键词：
Address Affect Aftercare Anhedonia Anxiety Behavior Behavioral Cellular Phone Characteristics Clinical Compassion Depressed mood Desire for food Dose Effectiveness Feeling suicidal Goals Individual Investigational Therapies Learning Love Measures Mediating Mediation Mediator of activation protein Mental Depression Motivation Outcome Participant Patient Self-Report Pharmacological Treatment Phase Physical activity Physiological Pilot Projects Positioning Attribute Positive Valence Process Protocols documentation Randomized Research Research Domain Criteria Rewards Schizophrenia Signal Transduction Social Interaction Specificity Stimulus Stress Substance abuse problem Suicide Symptoms System Technology Testing Therapeutic Time Training affective neuroscience anxious cognitive training design dosage effective therapy follow-up functional disability gratitude high risk improved indexing interest negative affect novel overtreatment pleasure psychologic psychosocial remote monitoring reward processing suicidal behavior therapy design treatment comparison treatment response

项目摘要

PROJECT SUMMARY Anhedonia, or loss of interest or pleasure in usual activities, is characteristic of depression, some types of anxiety, as well as substance abuse and schizophrenia. Anhedonia is a predictor of poor long term outcomes, including suicide, and poor treatment response. Extant psychological and pharmacological treatments are relatively ineffective for anhedonia. Thus, there is an unmet therapeutic need for this high-risk symptom. Recent advances in affective neuroscience have elucidated processes that may underlie anhedonia and should be targeted in therapy. Specifically, anhedonia is associated with deficits in the appetitive reward system, including (1) reward approach-motivation, (2) initial responsiveness to reward attainment, and (3) learning of reward. We have developed a novel transdiagnostic psychosocial treatment for anhedonia, Positive Affect Treatment (PAT), designed to improve deficits in reward sensitivity. In our pilot study of 61 depressed or anxious and functionally impaired individuals we found a strong preliminary efficacy signal and evidence for treatment specificity. Specifically, PAT led to significant improvements in symptoms of anhedonia, depression and anxiety and was more effective for individuals with anhedonia at baseline than a treatment designed to reduce negative affect. The proposed application uses an experimental therapeutics approach to elucidate whether reward approach- motivation, initial responsiveness to reward attainment or reward learning change with PAT (i.e., target engagement) in the R61 phase, and to evaluate whether changes in reward sensitivity mediate outcomes from PAT in the R33 phase. In the R61 phase, 68 individuals with anhedonia who are anxious or depressed and functionally impaired will be randomized to single-dose PAT (15 weekly sessions) or double dose PAT (PAT- DD, 30 twice-weekly sessions). Physiological, behavioral, and self-report measures of reward approach- motivation, initial reward responsiveness, and learning will be assessed repeatedly. Outcomes include clinician and self-report measures of anhedonia and ecologically valid measures of functional impairment (i.e., physical activity and social interaction). Progression to R33 depends on post-treatment average anhedonia scores that are within 1 SD of the norm, and significant (effect size > .8) pre- to post-treatment changes in reward approach- motivation, initial responsiveness to attainment or learning, which covary significantly with anhedonia over treatment. The treatment dose that produces significantly greater pre- to post-treatment change in one or more target measures will be carried forward to R33. In the R33 phase, 100 individuals will be randomized to PAT (or PAT-DD) or to Negative Affect Treatment; the latter designed to reduce threat sensitivity. Indices of reward sensitivity (from R33 phase) and threat sensitivity will be evaluated as mediators of PAT and moderated mediation will be tested by comparing reward sensitivity mediation in PAT vs NAT. If successful, PAT will offer a viable and effective treatment for individuals with anhedonia, and the results will elucidate the mechanisms responsible for the effectiveness of this novel treatment.

项目概要快感缺乏，或对日常活动失去兴趣或快乐，是抑郁症的特征，某些类型的焦虑症，以及药物滥用和精神分裂症。快感缺乏是长期不良结果的预测因素，包括自杀和治疗反应不佳。现有的心理和药物治疗方法有对于快感缺乏相对无效。因此，这种高风险症状的治疗需求尚未得到满足。最近的情感神经科学的进步已经阐明了可能是快感缺乏的基础过程，应该加以研究进行针对性的治疗。具体来说，快感缺乏与食欲奖励系统的缺陷有关，包括（1）奖励方法动机，（2）对奖励获得的初始反应，以及（3）奖励的学习。我们开发了一种针对快感缺失的新型跨诊断心理社会治疗方法，即积极情感治疗（PAT），旨在改善奖励敏感性的缺陷。在我们对 61 名抑郁或焦虑且功能障碍患者的初步研究中对于受损个体，我们发现了强有力的初步疗效信号和治疗特异性的证据。具体来说，PAT 显着改善了快感缺失、抑郁和焦虑症状，并且对于基线时有快感缺乏的个体来说，比旨在减少负面影响的治疗更有效。拟议的应用程序使用实验治疗方法来阐明奖励方法是否- 动机、对奖励达到或奖励学习变化的初始反应 PAT（即目标 R61 阶段的参与），并评估奖励敏感性的变化是否会介导以下结果： R33 阶段的 PAT。在 R61 阶段，68 名患有快感缺失、焦虑或抑郁的个体功能受损的患者将被随机分配至单剂量 PAT（每周 15 次）或双剂量 PAT（PAT- DD，30 次，每周两次）。奖励方法的生理、行为和自我报告测量- 动机、初始奖励反应和学习将被反复评估。结果包括临床医生快感缺失的自我报告测量和功能障碍的生态有效测量（即身体活动和社交互动）。进展至 R33 取决于治疗后平均快感缺乏评分与正常值的 1 SD 之内，并且奖励方法在治疗前和治疗后发生显着变化（效果大小 > .8）动机，对成就或学习的最初反应，与快感缺失显着相关治疗。在一种或多种治疗前后产生显着更大变化的治疗剂量目标措施将延续至 R33。在 R33 阶段，100 名个体将被随机分配至 PAT（或 PAT-DD）或负面影响治疗；后者旨在降低威胁敏感性。奖励指标敏感性（来自 R33 阶段）和威胁敏感性将作为 PAT 的中介进行评估并进行调节将通过比较 PAT 与 NAT 中的奖励敏感性中介来测试中介。如果成功，PAT 将提供为快感缺失患者提供可行且有效的治疗方法，其结果将阐明其机制负责这种新颖治疗方法的有效性。