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

晚年抑郁症的正价系统功能和奖赏暴露疗法

基本信息

批准号：
10438570
负责人：
Jennifer N Bress
金额：
$ 19.05万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10438570
关键词：
Adult Affective Age Aging Anhedonia Area Behavior Behavioral Biological Markers Brain Clinical Clinical Trials Design Collaborations Communities Complement Consultations Data Depressed mood Economic Burden Elderly Emotional Event-Related Potentials Feedback Functional disorder Generations Geriatric Psychiatry Goals Impairment Individual Institutes Intervention K-Series Research Career Programs Knowledge Major Depressive Disorder Manuscripts Matched Group Measures Mediating Mediator of activation protein Mental Depression Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Neurobiology Outcome Participant Patient Self-Report Physiology Pilot Projects Positive Valence Preparation Psychophysiology Psychotherapy Quality of life Reporting Research Research Domain Criteria Research Personnel Research Project Grants Research Training Rewards Role Series Severities Stimulus Supportive care Symptoms System Techniques Time Training Ventral Striatum Visual attention age group age related base biosignature career career development comparison group design effective therapy evidence base experience extrastriate geriatric depression high risk improved indexing learning community machine learning method novel opioid user peer predicting response recruit relating to nervous system research study response reward processing self reported behavior skills sustained attention trait

项目摘要

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.

项目概要/摘要拟议的 K23 指导的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，使其发展成为一名全面的独立心理生理学研究员研究抑郁症的生物标志物，可作为治疗目标与她的导师协商后，PI 招募了一个专家顾问团队来指导。她执行一个研究项目和培训计划，这将为她的目标提供必要的经验。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。该研究重点关注晚年抑郁症，因为它很普遍并且会产生负面后果。现有的治疗方法反应率低，并且由于其有效性而很少在社区中正确使用。该项目的前提是针对特定生物特征的集中治疗。神经异常对晚年抑郁症的临床结果影响最大。该项目将研究易受衰老影响且经常因抑郁症而受损的正价系统。研究接受“Engage”（一种心理治疗）的重度抑郁症老年人的正价系统旨在重新激活奖励系统功能的参与已被发现对晚年抑郁症和抑郁症有效。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 名抑郁的老年人（年龄 ≥ 60）进行了 Engage 的目标参与治疗，使用三个分析单元来评估正价系统功能：生理学（事件相关它将接受 Engage 治疗的参与者与 35 名抑郁症患者进行比较。参与者按年龄分组，接受手动支持治疗，将进行评估。无论是低基线正价函数，还是治疗期间正价函数增加，通过参与来预测快感缺乏的改善，以及奖励功能是否介导快感缺乏的变化。拟议的培训计划通过个性化的教程、正式的培训来补充研究性学习课程作业、研究合作和手稿准备将为 PI 提供知识和几个领域的技能：1）正价系统中与年龄相关的神经生物学变化以及相关 2) 先进的统计技术可识别抑郁症患者的明显神经异常基于他们的 ERP 概况；3) 心理治疗干预的临床试验设计。项目可能提供有关生物靶标参与和机制的重要信息知情且易于实施的晚年抑郁症治疗方法也将具有传播潜力。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 和 will 的反应在 PI 为独立研究生涯做准备时，她是她的重要垫脚石。