Reward Responsiveness as a Prevention Target in Youth At Risk for Anhedonia

将奖励反应作为快感缺失风险青少年的预防目标

• 批准号: 10722481
• 负责人: Katie L Burkhouse
• 金额: $ 73.68万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722481
• 关键词: 12 year old; Adult; Affect; Anhedonia; Behavioral; Biological; Brain; Buffers; Child; Clinical; Cognitive; Cognitive Therapy; Data; Development; Diagnostic; Dose; Ecological momentary assessment; Effectiveness; Electroencephalography; Family; Feedback; Health; Impairment; Intervention; Investigational Therapies; Life; Major Depressive Disorder; Measures; Mental Depression; Mental Health; Methods; Mothers; Motivation; National Institute of Mental Health; Neurosciences; Neurosciences Research; Outcome; Participant; Phase; Population; Positive Valence; Prevention; Prevention approach; Process; Psychopathology; Public Health; Randomized; Recording of previous events; Research Domain Criteria; Rewards; Risk; Symptoms; System; Testing; Translating; Work; Youth; affective neuroscience; clinical effect; comparison intervention; depressive symptoms; design; experience; follow up assessment; follow-up; high risk; individualized prevention; innovation; interest; negative affect; neural; offspring; personalized intervention; pleasure; positive emotional state; post intervention; precision medicine; prevent; preventive intervention; prospective; psychoeducation; psychoeducational; response; skills; suicidal; suicidal risk; symptomatic improvement; symptomatology; therapy resistant; treatment response

PROJECT SUMMARY Anhedonia, a core symptom of depression and other forms of psychopathology characterized by loss of interest or pleasure, is associated with a range of negative health outcomes, including suicide risk, and poor treatment response. Low activation of positive valence systems, particularly low reward responsiveness (RR), is a key brain-behavioral process underlying anhedonia. Critically, there is growing evidence that low RR is observable in children at risk for anhedonia due to maternal symptomatology and reflects a vulnerability for the later emergence of anhedonia and depression. Thus, targeting RR in high-risk children is critically needed to prevent the development of anhedonia, alter risk trajectories, and mitigate the tremendous health burden of anhedonia-related psychopathology. Combining principles from adult positive affect treatment and family cognitive behavioral preventive interventions, we developed an innovative, neuroscience-informed dyadic preventive intervention, Family Promoting Positive Emotions (F-PPE), for 8- to 12-year-old children and mothers with a history of major depressive disorder with anhedonia. F-PPE is designed to specifically target RR in children, assessed at the neural level using well-validated electroencephalogram methods. The first phase of the project (R61) will focus on target engagement, testing whether F-PPE increases child neural RR relative to an active comparison. Children (N=60) will complete neural measures of RR pre-intervention, 4- weeks into the intervention to determine dose effects, and post-intervention (8 weeks). Biological mother-child dyads will be randomized to F-PPE or a psychoeducation preventive intervention comparison. Target engagement will be defined as an increase in neural RR in the F-PPE relative to psychoeducation group with at least a medium effect size (d > .40). Change in the target at 4 weeks will be examined to determine dose effects and integrated with participant feedback to refine F-PPE for the R33 phase. The R33 phase will be a replication and extension to clinical outcomes with 100 biological mother-child dyads. Dyads will again be randomized to F-PPE or a comparable number of psychoeducation sessions. In addition to neural RR, ecological momentary assessment of real-world experiences of interest and pleasure and clinical symptoms of anhedonia will be assessed pre- and post-intervention and at a 6-month follow-up assessment. We will examine effects of F-PPE on momentary experiences of interest/pleasure and symptoms of anhedonia across the longitudinal follow-up and test change in RR as a mechanism of clinical effects of F-PPE. These projects will take critical next steps in translating developmental affective neuroscience research to prevention and moving towards precision medicine to reduce the burden of anhedonia and associated psychopathologies.

项目概要 快感缺乏，抑郁症和其他形式的精神病理学的核心症状，其特征是丧失 兴趣或快乐与一系列负面健康结果相关，包括自杀风险和贫困 治疗反应。正价系统的低激活，特别是低奖赏反应性（RR）， 是快感缺失背后的一个关键的大脑行为过程。至关重要的是，越来越多的证据表明，低 RR 是 在由于母亲症状而有快感缺失风险的儿童中可以观察到这一现象，这反映了儿童的脆弱性 后来出现快感缺乏和抑郁。因此，迫切需要针对高危儿童的 RR 预防快感缺乏的发展，改变风险轨迹，并减轻巨大的健康负担 快感缺失相关的精神病理学。结合成人积极情感治疗和家庭的原则 认知行为预防干预措施，我们开发了一种创新的、基于神经科学的二元疗法 针对 8 至 12 岁儿童的预防性干预措施，即家庭促进积极情绪 (F-PPE) 有快感缺失的重度抑郁症病史的母亲。 F-PPE 专门针对 使用经过充分验证的脑电图方法在神经水平上评估儿童的 RR。第一个 该项目的阶段（R61）将重点关注目标参与度，测试 F-PPE 是否会增加儿童神经 RR 相对于主动比较。儿童 (N=60) 将完成 RR 干预前的神经测量，4- 干预前几周以确定剂量效应，以及干预后（8周）。生物母子 双人组将被随机分配进行 F-PPE 或心理教育预防干预比较。目标 参与度将被定义为相对于心理教育组而言，F-PPE 中神经 RR 的增加 至少中等效应大小 (d > .40)。将检查 4 周时目标的变化以确定剂量 效果并与参与者的反馈相结合，以完善 R33 阶段的 F-PPE。 R33阶段将是 通过 100 个生物母子二人组复制和扩展临床结果。二人将再次成为 随机接受 F-PPE 或相当数量的心理教育课程。除了神经RR之外， 对真实世界的兴趣和快乐体验以及临床症状的生态瞬时评估 将在干预前和干预后以及 6 个月的随访评估中评估快感缺失。我们将 检查 F-PPE 对兴趣/愉悦的瞬间体验和快感缺失症状的影响 作为 F-PPE 临床效果机制的纵向随访和测试 RR 变化。这些项目 将采取关键的后续步骤，将发展情感神经科学研究转化为预防和治疗 迈向精准医学，以减轻快感缺失和相关精神病理学的负担。