Serotonin 1A Receptor PET Imaging and SSRI Outcome in Bipolar Depression

描述(申请人提供)：这项K23拨款申请的研究提案使用正电子发射断层扫描(PET)成像来量化双相抑郁症患者的大脑5-羟色胺1A受体，以确定成像信号是否与选择性5-羟色胺受体抑制剂(SSRI)抗抑郁剂氟西汀与情绪稳定剂的临床反应有关。与临床结果的关联可能是确定可以预测临床反应的生物标记物的第一步。这一目标很重要，因为并不是所有的双相患者对SSRI都有反应，而且治疗存在相关风险，这使得针对该疾病的个性化药物选择成为必要的工具。双相情感障碍很常见，是前十大残疾来源之一，并与自杀风险增加有关。此外，治疗是反复尝试的，这是一个有问题的临床过程，FDA只批准了三种药物用于抑郁症阶段。最近的一篇论文表明，脑5-羟色胺1A受体的PET信号与非结构化治疗3个月后的临床缓解有关。另一篇论文表明，PET信号与重度抑郁障碍患者对SSRI的临床反应有关。这项研究的另一个目的是确定PET信号是否与双相抑郁患者的焦虑或攻击性症状有关。如果存在相关性，这可能是根据生物学、5-羟色胺信号重新定义诊断的第一步。该项目使用了一种新的放射性示踪剂[11C]CUMI-101，这比其他放射性示踪剂有了显著的进步。它还利用一种新的统计方法将临床结果与成像数据相关联。这是一笔培训补助金，该研究项目将为其首席研究员、医学博士马丁·兰提供机会，使其发展成为 独立的神经影像研究人员。他以前有基础科学技术方面的研究背景，这笔赠款将使他能够获得以患者为导向的研究技能，以便在他的研究中使用他作为精神病学家的临床培训。在项目期间，他将得到该领域专家的指导，包括他的主要导师、共同导师J·约翰·曼博士、合作者R·托德·奥格登博士、帕特里克·麦格拉思博士和顾问杰弗里·迈耶博士。这种指导，以及增加他知识的课程，将提供图像处理、PET放射性示踪剂动力学建模、一般统计学以及基础神经科学和翻译神经科学方面的必要技能。

DESCRIPTION (provided by applicant): The research proposal for this K23 grant application uses imaging with positron emission tomography (PET) to quantify brain serotonin 1A receptors in bipolar depression to determine whether the imaging signal is associated with a clinical response to the selective serotonin receptor inhibitor (SSRI) antidepressant fluoxetine when added to a mood stabilizer. An association with clinical outcome may be a first step to identifying a biomarker that can predict clinical response. This goal is important because not all bipolar patients respond to SSRI's and there are risks associated with the treatment, making personalized medicine options for the disorder a needed tool. Bipolar disorder is common, is one of the top 10 sources of disability, and is associated with an increased risk for suicide. Moreover, treatment is trial and error, a problematic clinical process, and there are only three medications FDA approved for the depressed phase. A recent paper showed that PET signal of brain serotonin 1A receptor was associated with clinical remission after three months of unstructured treatment. A different paper showed that the PET signal was associated with clinical response to SSRI's in major depressive disorder. Another aim of the study is to determine whether the PET signal is associated with the symptoms of anxiety or aggression in bipolar depression. If there is a correlation, this may be the first step to redefining the diagnoss along biological, serotonin signaling. The project utilizes a new radiotracer [11C] CUMI-101 that is a significant advance over other radiotracers. It also utilizes a new statistical approach to correlate clinical outcome with imaging data. This is a training grant, and the research project will provide an opportunity for its principal investigator, Martin Lan, MD, PhD, to develop into an independent neuroimaging researcher. He has previous research background in basic science techniques, and this grant will allow him to gain patient oriented research skills to use his clinial training as a psychiatrist in his research. He will receive mentorship from experts in the field during the project, including his primary mentor, Dr. J John Mann, co-mentor, Dr. R. Todd Ogden, collaborator, Dr. Patrick McGrath and consultant, Dr. Jeffrey Meyer. This mentorship, and a curriculum of classes to increase his knowledge, will provide the necessary skills in image processing, PET radiotracer kinetic modeling, general statistics, and basic and translational neuroscience.