Expansion of the Dopaminergic Dysfunction in Late-Life Depression Study (The D3 Study)

晚年抑郁症中多巴胺能障碍研究的扩展（D3 研究）

• 批准号: 10793937
• 负责人: Warren D Taylor
• 金额: $ 157.29万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10793937
• 关键词: Academic Medical Centers; Administrative Supplement; Age; Aging; Award; Behavior assessment; Behavioral; Binding; Biometry; Brain; Carbidopa; Clinical; Clinical assessments; Cognitive; Corpus striatum structure; Crossover Design; Data; Data Analyses; Decision Making; Depressed mood; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Elderly; Enrollment; Evaluation; Exclusion; Executive Dysfunction; Exhibits; Expenditure; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Gait speed; Gender; Goals; Human Resources; Image; Impairment; Intervention; Levodopa; Link; Magnetic Resonance Imaging; Measurement; Measures; Mental Depression; Midbrain structure; Molecular; Motivation; Motor; National Institute of Mental Health; Neurocognitive; New York; Participant; Patient Recruitments; Patient Self-Report; Performance; Peripheral; Phase; Physical Performance; Placebos; Positive Valence; Positron-Emission Tomography; Prefrontal Cortex; Procedures; Publishing; Randomized; Research Domain Criteria; Resources; Rewards; Signal Transduction; Site; Speed; Statistical Data Interpretation; Structure; Substantia nigra structure; System; Universities; cognitive system; cognitive testing; cost; design; dopamine system; dopamine transporter; geriatric depression; improved; inflammatory marker; multimodality; neural; neuroimaging; neuromelanin; normal aging; pars compacta; processing speed; receptor density; recruit; reward processing; sensorimotor system; transmission process; willingness; young adult

PROJECT SUMMARY: This administrative supplement will expand scientific expertise and recruitment for the “Dopaminergic Dysfunction in Late-Life Depression” study. This proposal was originally funded as a collaborative R01 proposal between Columbia University/New York State Psychiatric Institute and Vanderbilt University Medical Center. As the Columbia site will no longer be contributing to this project, this supplement will provide support for the Vanderbilt site to: a) have the required scientific expertise to achieve study goals; b) provide budgetary support for study procedures previously covered by Columbia University; and c) expand enrollment to reach goals comparable to the funded collaborative proposal. The overall objective of the funded proposal does not change with this supplement. This supplement supports an expansion of the study that will allow us to achieve the funded study goals without Columbia University. Expansion of scientific expertise includes involvement of new personnel with expertise in biostatistics, PET imaging, MRI-based neuromelanin imaging, and peripheral inflammatory markers. It will support procedures previously supported by Columbia, specifically statistical analyses, the analyses of some neuroimaging data (Neuromelanin-MRI and [18F]-FDOPA PET) and analyses of inflammatory markers by Emory University. It will also support the expansion of recruitment beyond what was initially planned at the Vanderbilt site, expanding recruitment both at Vanderbilt and at a new subcontracted site at the University of Pittsburgh. These changes provide the scientific expertise and resources to achieve the goals of the originally funded study while maintaining statistical power. Study procedures have not substantially changed. We will enroll cumulatively 70 psychiatrically healthy elders and 100 depressed elders exhibiting likely dopaminergic dysfunction, characterized as either slowed processing speed or slowed motor speed. Participants undergo clinical characterization and complete PET imaging measuring dopamine synthesis and dopamine receptor availability, neuromelanin-sensitive MRI measurement of long-term nigrostriatal dopamine transmission, task positive MRI focused on effort-based decision making and reward processing, a comprehensive neurocognitive evaluation, a physical performance evaluation, and measurement of inflammatory markers. To assess responsivity of the dopamine system to modulation, depressed subjects are then randomized to L-DOPA or placebo for 3 weeks, followed by repeat multimodal MRI and cognitive/behavioral assessments. Using a cross-over design, participants will receive the opposite intervention for an additional 3 weeks followed by clinical and cognitive assessments only. These procedures have been feasible and well tolerated with ongoing enrollment at Vanderbilt.

项目摘要：这一行政补编将扩大科学专门知识和招聘工作 《老年抑郁症患者的多巴胺能功能障碍》研究。这项提议最初是作为一项 哥伦比亚大学/纽约州立精神病研究所与范德比尔特合作的R01提案 大学医学中心。由于哥伦比亚网站将不再为该项目做出贡献，本增刊 将为Vanderbilt网站提供支持：a)拥有实现研究目标所需的科学专门知识；b) 为以前由哥伦比亚大学涵盖的研究程序提供预算支持；以及c)扩大 注册以达到与资助的协作计划书相当的目标。基金的总体目标 建议不会因本补充资料而改变。 本附录支持扩大研究范围，使我们能够实现资助的研究目标。 没有哥伦比亚大学。科学专门知识的扩展包括新人员的参与 在生物统计学、PET成像、基于MRI的神经黑色素成像和外周炎症方面的专业知识 记号笔。它将支持哥伦比亚大学以前支持的程序，特别是统计分析、 部分神经影像资料(神经黑素-MRI和[18F]-FDOPA PET)分析及炎性病变分析 埃默里大学的记分员。它还将支持扩大招聘范围，使其超出最初的范围 计划在范德比尔特工地，扩大在范德比尔特和 匹兹堡大学。这些变化为实现以下目标提供了科学专门知识和资源 在保持统计力量的同时，最初资助的研究。 研究程序并没有实质性的改变。我们将招收累计70名精神健康的人 老年人和100名抑郁的老年人表现出可能的多巴胺能功能障碍，特征是要么减慢 处理速度或减慢电机速度。参与者接受临床特征和完整的PET检查 神经黑素敏感型核磁共振成像测量多巴胺合成和多巴胺受体可用性 测量长期黑质纹状体多巴胺传递，任务阳性磁共振侧重于努力型 决策和奖励处理，全面的神经认知评估，体能表现 炎症标志物的评估和测量。为了评估多巴胺系统对 调制，然后抑郁症患者被随机给予L多巴或安慰剂治疗3周，然后重复 多模式核磁共振和认知/行为评估。使用交叉设计，参与者将获得 相反的干预再进行3周，之后只进行临床和认知评估。这些 范德比尔特大学正在进行的招生程序是可行的，也是可以容忍的。

项目成果

Influences of dopaminergic system dysfunction on late-life depression.

• DOI: 10.1038/s41380-021-01265-0
• 发表时间: 2022-01
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Taylor WD;Zald DH;Felger JC;Christman S;Claassen DO;Horga G;Miller JM;Gifford K;Rogers B;Szymkowicz SM;Rutherford BR
• 通讯作者: Rutherford BR