IMAGING THE DEPRESSION/DEMENTIA INTERACE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这一修订后的申请在以患者为导向的研究（K24）的中期职业研究者奖旨在提供候选人，神经放射科医生和核医学医生与现有的广泛的正电子发射断层扫描（PET）成像经验，与重点研究和额外的培训支持机制之间的接口晚年抑郁症和痴呆症，并指导活动。该奖项将适用于NIMH资助的R 01（MH 59945），该研究采用PET研究晚年抑郁症的中枢神经系统功能。晚年抑郁症会增加痴呆症的风险，对治疗的反应也会变弱。R 01支持的研究计划需要对与抑郁症和抗抑郁药物治疗机制密切相关的两个重要标志物进行定量成像：5-HT 1A受体和5-HT转运体，在患有严重抑郁症的未治疗老年患者和年龄、性别匹配的对照中对这两个部位进行PET成像将测试晚年抑郁症的模型，包括我们的假设，即前额叶皮质中的5-HT 1A结合将预测治疗反应性，海马5-HT 1A结合将与基线认知障碍相关，更重要的是，与痴呆风险相关。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。由于遗传学研究可能会在未来的调查工作中发挥重要作用，旨在确定患有痴呆症的高风险人群并评估抗抑郁治疗的反应性，候选人寻求培训，使她能够成为多学科研究团队的受过教育的成员，使用遗传和各种体内成像标记来研究痴呆症风险及其与晚年抑郁症的联系。这些元素是由一个指导计划的补充，支持候选人的进一步发展，作为一个导师的两个医学博士。和博士培训学员进行以患者为导向的神经影像学研究。该K24应用扩展了PI的NIMH支持的I级K奖（K 07）在晚年精神障碍中5-HT系统PET成像方面的工作。当前提案的目的是为候选人提供25%的保护时间，以：1）扩大她在指导神经成像初级临床神经科学家方面的努力，2）获得高级培训，以应对设计和实施未来大规模调查工作的挑战，将专门的PET成像技术应用于脑老化研究。

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.