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

项目总结/摘要 拟议的K23指导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，以发展成为一个全面的 独立的心理生理学研究人员研究抑郁症的生物标志物，可作为目标， 新的干预措施。在与她的导师协商后，PI招募了一个专家顾问团队， 她在执行一个研究项目和培训计划，将提供必要的经验，她的目标。 拟议的研究将在威尔康奈尔老年医学研究所的ALACRITY中心进行 精神病学。这项研究的重点是晚年抑郁症，因为它是普遍的，并有负面的结果。 现有的治疗方法的反应率很低，而且由于其局限性， 复杂性该项目的前提是，针对特定生物特征的集中治疗 神经异常将对晚年抑郁症的临床结果产生最大的影响。它集中 积极的效价系统，这是脆弱的老化，往往在抑郁症受损。该项目将 研究接受Engage心理治疗的老年抑郁症患者的正效价系统 旨在重新激活奖励系统功能参与已被发现对晚年抑郁症有效， 容易被社区治疗师学习。与RDoC方法一致，拟议的研究将检查 在为期9周的Engage课程中，对35名老年抑郁症患者（年龄≥ 60岁）进行Engage目标参与 治疗，使用三个分析单位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。它将比较参与治疗的参与者和35名抑郁症患者， 参与者，年龄组匹配，接受手动支持治疗。其他分析将评估 无论是低基线正效价功能，还是治疗期间正效价功能的增加， 用Engage预测快感缺失的改善，以及奖赏功能是否介导快感缺失的改变。 拟议的培训计划补充了研究性学习与个性化的辅导，正式 课程作业，研究合作和手稿准备，将提供PI的知识和 几个方面的技能：1）与神经生物学有关的正效价系统的变化和相关的 网络; 2）先进的统计技术，以确定不同的神经异常抑郁症患者 基于他们的ERP概况;和3）心理治疗干预的临床试验设计。拟议 该项目可能提供有关生物学上的靶向参与和机制的重要信息。 知情，易于实施的治疗晚年抑郁症，有可能传播。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Engage的反应， 作为一个重要的垫脚石PI，因为她准备一个独立的研究生涯。

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.