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.

项目摘要 Anhedonia或在通常的活动中失去兴趣或愉悦的丧失是抑郁的特征，某些类型的焦虑以及药物滥用和精神分裂症。 Anhedonia是长期不良结果的预测指标，包括自杀和治疗反应不佳。现有的心理和药理治疗是对狂欢节相对无效。因此，对这种高风险症状存在未满足的治疗需求。最近的情感神经科学的进步已经阐明了可能是Anhedonia的过程，应该是针对治疗。具体而言，Anhedonia与食欲奖励系统中的缺陷有关，包括（1）奖励运动动机，（2）对奖励成就的最初响应能力，以及（3）学习奖励。我们已经开发了一种新型的经诊断性的心理社会心理治疗，以阳性影响（PAT），旨在改善奖励灵敏度的缺陷。在我们对61个沮丧或焦虑和功能的试点研究中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。具体而言，PAT导致了Anhedonia，抑郁和焦虑的症状显着改善，并且是对于基线时的Anhedonia患者而言，比旨在减少负面影响的治疗更有效。拟议的应用采用实验治疗方法来阐明奖励方法是否奖励 - 动机，最初的响应能力奖励成就或奖励学习变革（即目标）参与）在R61阶段，并评估奖励灵敏度的变化是否介导在R33阶段进行PAT。在R61阶段，有68名焦虑或沮丧的人患有Anhedonia的人功能受损的人将被随机分为单剂量PAT（每周15次）或双剂量PAT（PAT- DD，每周两次两次）。奖励方法的生理，行为和自我报告衡量标准 - 动机，最初的奖励响应能力和学习将被反复评估。结果包括临床医生和自我报告的态度和生态有效的功能障碍措施（即物理障碍）活动和社交互动）。到R33的进展取决于治疗后平均Anhedonia得分在规范的1个SD之内，并且在奖励方法中的显着（效应大小> .8）在治疗前变化 - 动机，最初对成就或学习的反应能力治疗。在一个或多个的治疗后剂量变化明显更大的治疗剂量目标措施将提交到R33。在R33阶段，将有100个人随机进行PAT（或 pat-dd）或负面影响治疗；后者旨在降低威胁敏感性。奖励指标灵敏度（来自R33阶段）和威胁敏感性将作为PAT的调解人评估将通过比较PAT与NAT中的奖励灵敏度中介来测试调解。如果成功，帕特将提供对Anhedonia的个体进行可行有效的治疗方法，结果将阐明机制负责这种新型治疗的有效性。