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

• 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
• 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

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.

项目总结 快感缺乏，或在日常活动中失去兴趣或快乐，是抑郁症的特征，某些类型的 焦虑，以及药物滥用和精神分裂症。快感缺乏是长期结果不佳的预兆， 包括自杀、治疗反应差等。现有的心理和药物治疗是 对快感缺乏症相对无效。因此，对这种高危症状的治疗需求尚未得到满足。近期 情感神经科学的进展已经阐明了可能导致快感缺失的过程，并且应该 在治疗中有针对性。具体地说，快感缺乏与胃口奖励系统的缺陷有关，包括 (1)奖励方式--动机；(2)对奖励获得的初始反应；(3)奖励的学习。我们 开发了一种治疗快感缺乏症的新的跨诊断心理社会疗法，积极情感疗法(PAT)， 旨在改善奖励敏感度方面的缺陷。在我们对61名抑郁或焦虑和功能性疾病的初步研究中 对于受损的个体，我们发现了强烈的初步疗效信号和治疗特异性的证据。 具体地说，帕特显著改善了快感缺乏、抑郁和焦虑的症状，并 对于基线水平的快感缺乏症患者，比旨在减少负面影响的治疗更有效。 拟议的申请使用了一种实验治疗学的方法来阐明奖励方法- 动机、对获得奖励的初始反应或奖励学习随PAT(即目标)的变化 在R61阶段)，并评估奖励敏感度的变化是否在 在R33阶段的PAT。在R61阶段，68名焦虑或抑郁的快感缺乏患者和 功能受损的患者将随机接受单剂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、行为和自我报告措施- 动机、最初的奖励反应和学习将被反复评估。结果包括临床医生 以及快感缺乏的自我报告措施和功能损害的生态有效措施(即，身体 活动和社交)。进展到R33取决于治疗后快感缺乏症的平均评分 在正常范围内，且治疗前后奖励方法的显著变化(效果大小)： 动机，对成就或学习的初始反应，这与快感缺乏有关 治疗。在一个或多个治疗前后产生显著更大变化的治疗剂量 目标措施将结转到R33。在R33阶段，100个人将被随机分配到PAT(或 PAT-DD)或负面影响治疗；后者旨在降低对威胁的敏感性。奖励指数 敏感度(从R33阶段开始)和威胁敏感度将作为PAT和缓和的中介进行评估 将通过比较PAT和NAT中的奖励敏感度中介来测试中介。如果成功，帕特将提供 一种可行而有效的治疗快感缺乏症的方法，其结果将阐明其机制 对这种新疗法的有效性负责。