Positive Valence System Function and Reward Exposure Therapy for Late-Life Depression

项目摘要/摘要 拟议的K23以患者为导向的研究职业发展奖的目标是 为PI提供指导、理论知识和研究技能，使其发展成为一个 研究抑郁症生物标记物的独立心理生理学研究人员，可作为治疗抑郁症的靶标 新颖的干预措施。在咨询了她的导师后，PI聘请了一支专家顾问团队来指导 她在执行研究项目和培训计划方面发挥了重要作用，这将为她的目标提供必要的经验。 这项拟议的研究将在威尔康奈尔老年医学研究所的快活中心进行 精神病学。这项研究关注的是晚年抑郁症，因为它很普遍，而且会带来负面后果。 现有的治疗方法应答率低，很少在社区中正确使用，因为它们 复杂性。该项目基于这样的前提，即针对特定生物签名的重点治疗 神经异常将对老年抑郁症的临床结果产生最大影响。它浓缩了 在正价系统上，它很容易老化，而且经常在抑郁症中受损。该项目将 对接受心理治疗的患有重度抑郁症的老年人的正性价态系统进行调查 旨在重新激活奖励系统功能。参与被发现对老年抑郁症和 社区治疗师很容易学习。与RDoC方法一致，拟议的研究将审查 35名老年抑郁症患者(60岁，≥)在9周参与过程中参与目标 治疗，使用三个单元的分析来评估正价系统功能：生理学(事件相关 潜力)、自我报告和行为。它将对接受敬业度治疗的参与者和35名抑郁症患者进行比较 参与者在年龄上分组匹配，接受手动支持治疗。其他分析将评估 无论是基线正价函数偏低，还是治疗期间正价函数升高， 使用Engage预测快感缺失的改善，以及奖赏功能是否中介快感缺失的改变。 拟议的培训计划与研究性学习相辅相成，提供正式的个性化教程 课程、研究合作和手稿准备，将为PI提供知识和 以下几个领域的技能：1)正价系统中与年龄相关的神经生物学变化 网络；2)先进的统计技术，以识别抑郁个体的明显神经异常 基于他们的事件相关电位资料；以及3)心理治疗干预的临床试验设计。建议数 项目可提供有关靶参与和生物机制的重要信息 对有传播潜力的晚年抑郁症进行知情、易于实施的治疗。它还将 使用机器学习方法为R系列研究提供试点数据，以预测对接洽和意愿的反应 作为PI为独立研究事业做准备的重要垫脚石。

Project Summary/Abstract The goal of the proposed K23 Mentored Patient-Oriented Research Career Development Award is to provide the PI with the mentorship, theoretical knowledge, and research skills to develop into a fully independent psychophysiological researcher studying biomarkers of depression that can be used as targets for novel interventions. In consultation with her mentors, the PI has recruited a team of expert consultants to guide her in executing a research project and training plan that will provide experience essential to her goals. The proposed study will be conducted at the ALACRITY Center of the Weill Cornell Institute of Geriatric Psychiatry. The study focuses on late-life depression because it is prevalent and has negative outcomes. Existing treatments have low response rates and are rarely used correctly in the community due to their complexity. The project is based on the premise that focused treatments targeting biosignatures of specific neural abnormalities will have the greatest impact on clinical outcomes in late-life depression. It concentrates on positive valence systems, which are vulnerable to aging and often impaired in depression. The project will investigate positive valence systems in older adults with major depression receiving Engage, a psychotherapy designed to reactivate reward system functions. Engage has been found efficacious in late-life depression and easy to learn by community-based therapists. Consistent with RDoC methods, the proposed study will examine target engagement of Engage in 35 depressed older adults (age ≥ 60) during a 9-week course of Engage therapy, using three units of analysis to assess positive valence system function: physiology (event-related potentials), self-reports, and behavior. It will compare Engage-treated participants with 35 depressed participants, group-matched on age, receiving manualized supportive therapy. Additional analyses will assess whether low baseline positive valence function, or increases in positive valence function during treatment, predict improvement of anhedonia with Engage, and whether reward function mediates change in anhedonia. The proposed training plan complements the research study with individualized tutorials, formal coursework, research collaborations, and manuscript preparation that will provide the PI with knowledge and skills in several areas: 1) Age-related neurobiological changes in the positive valence system and related networks; 2) Advanced statistical techniques to identify distinct neural abnormalities in depressed individuals based on their ERP profiles; and 3) Clinical trial design for psychotherapeutic interventions. The proposed project may provide important information about target engagement and mechanisms of a biologically informed, easily implemented treatment for late-life depression that has potential for dissemination. It will also provide pilot data for an R-series study using machine learning methods to predict response to Engage and will serve as an important stepping-stone for the PI as she prepares for an independent research career.