Neurobiological Mechanisms of Treatment Response in Geriatric Depression

描述（由申请人提供）：这是K-24面向患者研究（POR）的中期职业研究者奖申请的重新提交。该奖项的目的是支持Helen Lavretsky医学博士的职业发展，她致力于了解老年抑郁症治疗反应的潜在神经生物学机制。职业发展计划将允许候选人：(1)发展功能神经成像的专业知识，专注于[F-18]fallypride正电子发射断层扫描（PET），这与她正在进行的哌醋甲酯在老年抑郁症中的多巴胺能机制的研究相关；(2)通过建议的课程和教程扩展她的知识和技能，以使用功能磁共振成像（fMRI）；(3)提高她领导临床研究的能力，利用生物标志物关注老年情绪障碍合并认知障碍或照顾者压力患者的治疗反应；(4)提高她的指导技能，以及她招募和指导代表性不足的少数民族和女性学员的能力。指导计划针对的是那些想要学习设计和实施以患者为导向的老年情绪障碍研究的初级研究者。在候选人的指导下，受训者将通过进行老年情绪障碍的研究，准备科学报告和入门级K奖来获得实践经验。该研究计划的重点是试点使用[F-18]fallypride PET来研究在哌甲酯（MPH）增强西酞普兰的临床试验背景下增强多巴胺能神经传递的作用，以改善16名老年抑郁症患者的临床和认知结果。本研究的主要目的是证明，与服用西酞普兰+安慰剂的受试者相比，服用西酞普兰的MPH受试者在抑郁严重程度上有更大的下降，在执行认知测试中有更大的改善，这将与[(18)F]的大百分比变化有关。在此奖项的支持下，本申请中提出的额外工作将集中在心身干预对老年抑郁症的使用和机制上。

DESCRIPTION (provided by applicant): This is a resubmission of an application for a K-24 Midcareer Investigator Award in patient-oriented research (POR). The objectives of the award is to support career development of Helen Lavretsky, M.D. dedicated to understanding the underlying neurobiological mechanisms of treatment response in geriatric depression. The Career Development Plan will allow the candidate to: (1) develop an expertise in functional neuroimaging focused on the [F-18]fallypride positron emission tomography (PET) that is relevant to her ongoing investigation of the dopaminergic mechanisms of methylphenidate in geriatric depression; (2) extend her knowledge and skills to the use of functional MRI (fMRI) with the proposed coursework and tutorials; (3) enhance her ability to lead clinical studies with the use of biomarkers focused on treatment response in older patients with mood disorders complicated by cognitive impairment or caregiver stress; (4) improve her mentoring skills and her ability to recruit and mentor underrepresented minority and women trainees. The Mentoring Plan is targeted towards beginning investigators who want to learn to design and conduct patient-oriented research in late-life mood disorders. Under supervision by the candidate, trainees will obtain hands-on experience by conducting research in geriatric mood disorders, and by preparing scientific reports and entry-level K awards. The Research Plan is focused on the pilot use of the [F-18]fallypride PET to investigate the role of enhanced dopaminergic neurotransmission in the context of the clinical trial of methylphenidate (MPH) augmentation of citalopram to enhance clinical and cognitive outcomes in 16 subjects with geriatric depression. The primary aims of this study are to demonstrate that subjects receiving MPH with citalopram will experience greater decrease in the severity of depression and improvement in executive cognitive tests compared to those receiving citalopram+placebo, which will be related to the greater percent change in [(18)F] fallypride striatal/nonstriatal BP. With the support of this award, additional work proposed in this application will focus on the use and the mechanisms of mind-body interventions for geriatric depression. PUBLIC HEALTH RELEVANCE: This is a grant application for a K-24 Mid-career Development Award to assist the candidate's transition to becoming a primary research mentor for junior colleagues in the area of developing optimal treatments for geriatric depression focused on the investigation of the underlying neurobiological mechanisms of treatment response. The application is based on two funded projects and an additional pilot project proposing to investigate dopamine neurotransmitter function in treatment outcomes of geriatric depression.