IMAGING THE DEPRESSION/DEMENTIA INTERACE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本次修订后的以患者为中心的研究生涯中期研究人员奖(K24)的申请旨在为候选人，一名神经放射学家和核医学内科医生，具有丰富的正电子发射断层扫描(PET)成像经验，支持在晚年抑郁症和痴呆症之间的潜在机制方面的重点研究和额外培训，以及指导活动。该奖项将适用于NIMH资助的R01(MH59945)，该项目通过PET研究老年抑郁症的中枢5-羟色胺能功能。晚年的抑郁症增加了患痴呆症的风险，对治疗的反应也很脆弱。R01支持的研究计划需要对两个与抑郁和抗抑郁药物治疗机制密切相关的重要标记物：5-HT1A受体和5-HT转运体进行定量成像，并对这两个部位进行PET成像。在未经治疗的患有严重抑郁症的老年患者中，性别匹配对照将测试一个晚年抑郁模型，其中包括我们的假设，即5-HT1A在前额叶皮质的结合将预测治疗反应性，而海马区5-HT1A的结合将与基线认知障碍，更重要的，痴呆风险相关。职业发展将包括阿尔茨海默病的基本机制和临床方面的培训。由于基因研究可能在未来旨在识别痴呆症高危人群和评估抗抑郁药物治疗反应性的调查工作中发挥重要作用，候选人寻求培训，使她能够成为一个多学科研究团队的受过教育的成员，使用基因和各种体内成像标记物来研究痴呆症风险及其与晚年抑郁的联系。与这些需求相辅相成的是一项指导计划，该计划支持候选人在面向患者的神经成像研究中进一步发展成为医学博士和博士受训人员的导师。这个K24应用程序扩展了PI的NIMH支持的Level I K-AWARD(K07)在晚期精神障碍的5-羟色胺系统PET成像方面的工作。当前建议的目的是为候选人提供25%的保护时间，以：1)扩大她在神经成像方面指导初级临床神经科学家的努力，以及2)获得高级培训，以应对设计和实施未来将专门的PET成像技术应用于脑老化研究的大规模研究工作的挑战。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This revised application for a Midcareer Investigator Award in Patient-Oriented Research (K24) seeks to provide the candidate, a neuroradiologist and nuclear medicine physician with existing extensive positron emission tomography (PET) imaging experience, with support for focused research and additional training in mechanisms underlying the interface between late-life depression and dementia, and for mentoring activities. This award will be applied to an NIMH-funded R01 (MH59945) investigating central serotonergic function in late-life depression with PET. Depression in late life carries an increased risk of dementia and brittle response to treatment. The R01-supported Research Plan entails quantitative imaging of two important markers strongly implicated in depression and mechanisms of antidepressant pharmacotherapy: the 5-HT1A receptor and the 5-HT transporter, PET imaging of these two sites in untreated elderly patients with major depression and age, gender-matched controls will test a model of late-life depression, including our hypotheses that 5-HT1A binding in the prefrontal cortex will be predictive of treatment responsivity and hippocampal 5-HT1A binding will correlate with baseline cognitive impairment and, more importantly, dementia risk. Career Development will incorporate training in basic mechanisms and clinical aspects of Alzheimer's disease. Since genetic studies will likely play a substantial role in future investigative efforts aimed at identifying persons at high risk for developing dementia and assessing antidepressant treatment responsivity, the candidate seeks training that will enable her to be an educated member of a multi-disciplinary research team using both genetic and a variety of in vivo imaging markers to study dementia risk and its link to late-life depression. These dements are complemented by a Mentoring Plan supportive of the candidate's further development as a mentor of both M.D. and Ph.D. trainees in the conduct of patient-oriented neuroimaging research. This K24 application extends the PI's NIMH-supported level I K-award (K07) work in PET imaging of the 5-HT system in late-life mental disorders. The purpose of the current proposal is to provide the candidate with 25% protected time to: 1) expand her efforts in mentoring junior clinical neuroscientists in neuroimaging, and 2) to acquire advanced training that will meet the challenges of designing and implementing future large-scale investigative efforts to apply specialized PET imaging techniques to studies of brain aging.