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

项目摘要 快感缺失，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有关，包括自杀风险，以及贫穷。 治疗反应。积极效价系统的低激活，特别是低奖励反应（RR）， 是导致快感缺失的关键大脑行为过程重要的是，越来越多的证据表明，低RR 观察到的风险为快感缺失的儿童由于孕产妇生殖系统，并反映了脆弱性， 随后出现快感缺乏和抑郁。因此，迫切需要在高危儿童中开展RR， 预防快感缺乏的发展，改变风险轨迹，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，我们开发了一个创新的，神经科学知情的二元 - 针对8至12岁儿童的预防性干预-家庭促进积极情绪， 母亲有重度抑郁症伴快感缺乏病史。F-PPE专门针对 儿童RR，使用经过充分验证的脑电图方法在神经水平上进行评估。第一 该项目的第一阶段（R61）将侧重于目标参与，测试F-PPE是否会增加儿童神经RR 相对于积极的比较。儿童（N=60）将在干预前完成RR的神经测量，4- 干预后7周以确定剂量效应，以及干预后（8周）。亲生母子 二人组将被随机分配到F-PPE或心理教育预防干预比较组。目标 参与度将被定义为F-PPE中神经RR相对于心理教育组的增加， 至少中等效应量（d > .40）。将检查4周时目标的变化以确定剂量 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 100对生物学母子配对的临床结果的复制和扩展。二元组将再次成为 随机分配到F-PPE或相当数量的心理教育课程。除了神经RR， 对现实世界的兴趣和快乐体验以及临床症状进行生态瞬时评估 将在干预前和干预后以及6个月随访评估时评估快感缺失。我们将 检查F-PPE对兴趣/快乐的瞬间体验和快感缺失症状的影响， RR的纵向随访和试验变化是F-PPE临床效应的机制。这些项目 将采取关键的下一步措施，将发展情感神经科学研究转化为预防， 迈向精准医疗，以减轻快感缺乏和相关精神病理学的负担。

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.