Mentoring and Research on Neurobiological Markers of Clinical Outcomes in Depression

这是一个新提交的K24职业生涯中期研究人员奖，以患者为中心的研究。 这项提案的首要目标是允许候选人沃伦·D·泰勒(Warren D.Taylor，MD) 培养PET成像方面的专业知识，2)获得指导初级员工的技能和经验 研究人员。这将扩展他过去研究临床结果的生物标记物的工作 抑郁症的细胞和分子指标，同时指导新的研究人员 生物标记物方法检查重要的临床结果。为了实现这些目标， 职业发展计划规定了PET成像方法学和方法方面的培训 分析PET成像数据，以及将PET和 核磁共振数据。他的指导技能将通过担任当地和 国家辅导研讨会、正式培训，并致力于制定研究培训计划。 为了支持这些目标，指导计划将重点放在以患者为导向的初级调查人员身上 对抑郁症感兴趣的研究。利用多个Vanderbilt资源来识别和 支持这些受训者，应聘者将提供研究方法的实践培训 目标是培训学员准备可发表的科学报告和入门级补助金 申请。范德比尔特的广泛机构资源将增强所提供的经验 由候选人主持。最后，应聘者的职业发展侧重于发展以下方面的专长 研究计划将促进PET成像。这一试点项目涉及获得 老年抑郁症患者的氟倍他平(18F)PET数据，主要目的是 研究淀粉样蛋白沉积对认知和抗抑郁结果的作用。这 该项目与候选人目前的R01有关，这是一项检查结构和功能磁共振的研究 影响抗抑郁药物治疗结果的生物标志物。通过获取淀粉样蛋白的数据 在33名认知正常但抑郁的个体中，该项目将检验这些假说 淀粉样蛋白结合量的增加与较差的认知表现和较差的 对8周盲用依西他普兰的反应。通过将PET数据与MRI数据集成，我们 我还将研究这种影响是否与默认模式下的早期淀粉样蛋白沉积有关 网络区域，以及淀粉样蛋白沉积是否与网络功能改变有关 连通性。总体而言，这一奖项将为候选人扩大他的 研究专业知识和指导计划。它还将提供有关效果的新信息 阿尔茨海默病神经病理学对晚年抑郁症结果的影响，将指导未来的提案。

This is a new submission for a K24 Midcareer Investigator Award in Patient-Oriented Research. The overarching objective of this proposal is to allow the Candidate, Warren D. Taylor, MD, to 1) develop expertise in PET imaging and 2) obtain skills and experience in mentoring junior researchers. This will extend his past work examining biomarkers of clinical outcomes in depression into cellular and molecular measures while mentoring new investigators on biomarker approaches examining important clinical outcomes. To achieve these goals, the Career Development Plan provides for training in PET imaging methodology, methods for analyzing PET imaging data, and methods for multimodal imaging analyses combining PET and MRI data. His mentorship skills will be enhanced through by serving as faculty for local and national mentoring workshops, formal training, and work to develop a research training program. Supporting these goals, the Mentoring Plan focuses on junior investigators in patient-oriented research with interests in depression. Utilizing multiple Vanderbilt resources to identify and support these trainees, the Candidate will provide hands-on training in research methodology with the goal of trainees preparing publishable scientific reports and entry-level grant applications. Extensive institutional resources at Vanderbilt will augment experiences provided by the Candidate. Finally, the Candidate's career development focus on developing expertise in PET imaging will be facilitated by the Research Plan. This pilot project involves obtaining florbetapir (18F) PET data in older adults with depression with the overarching aim of investigating the role of amyloid deposition on cognition and antidepressant outcomes. This project is linked to the Candidate's current R01, a study examining structural and functional MRI biomarkers influencing antidepressant treatment outcomes. By acquiring data on amyloid binding in 33 cognitively intact but depressed individuals, this project will test the hypotheses that increased amyloid binding is associated with poorer cognitive performance and poorer response to 8 weeks of blinded escitalopram. By integrating the PET data with MRI data, we will also examine whether this effect is related to early amyloid deposition in default mode network regions, and whether amyloid deposition is associated with altered network functional connectivity. Overall, this award will provide crucial support for the Candidate to expand his research expertise and mentoring programs. It will also provide novel information on the effects of Alzheimer neuropathology on late-life depression outcomes that will guide future proposals.