Mentoring and Research on Neurobiological Markers of Clinical Outcomes in Depression

这是一个新的提交K24中期职业生涯研究者奖在以患者为导向的研究。 这项提案的首要目标是让候选人沃伦·D·泰勒，MD，1） 发展PET成像方面的专业知识，2）获得指导初级 研究人员这将扩展他过去的工作，检查临床结果的生物标志物， 抑郁症的细胞和分子措施，同时指导新的研究人员， 生物标志物方法检查重要的临床结果。为了实现这些目标， 职业发展计划提供PET成像方法、 分析PET成像数据的方法以及用于结合PET和 MRI数据。他的指导技能将通过担任教师，为当地和 国家指导讲习班，正式培训，并努力制定研究培训计划。 为了支持这些目标，指导计划侧重于以患者为导向的初级研究者 对抑郁症感兴趣的研究。利用多个范德比尔特的资源，以确定和 为了支持这些学员，候选人将提供研究方法方面的实践培训 目的是让受训人员编写可供参考的科学报告， 应用.在范德比尔特广泛的机构资源将增加经验提供 候选人。最后，候选人的职业发展侧重于发展以下方面的专业知识： 研究计划将促进PET成像。该试点项目涉及获得 florbetapir（18F）在老年抑郁症患者中的PET数据，总体目的是 研究淀粉样蛋白沉积对认知和抗抑郁疗效的作用。这 该项目与候选人目前的R01有关，R01是一项检查结构和功能MRI的研究 影响抗抑郁治疗结果的生物标志物。通过获取淀粉样蛋白的数据 结合33个认知完整但抑郁的个体，该项目将测试假设 淀粉样蛋白结合的增加与认知能力的下降和 对8周盲态艾司西酞普兰的反应。通过将PET数据与MRI数据相结合， 还将研究这种效应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改变的网络功能相关。 连通性。总的来说，这个奖项将为候选人提供关键的支持，以扩大他的 研究专长和指导计划。它还将提供有关影响的新信息， 老年痴呆症神经病理学对晚年抑郁症的影响，这将指导未来的建议。

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.