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

双相抑郁症中血清素 1A 受体 PET 成像和 SSRI 结果

• 批准号: 8934160
• 负责人: Martin Joseph Lan
• 金额: $ 18.04万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8934160
• 关键词: Acute; Adult; Affect; Aftercare; Aggressive behavior; Agitation; Antidepressive Agents; Anxiety; Applications Grants; Autoreceptors; Basic Science; Binding; Biological; Biological Markers; Bipolar Depression; Bipolar Disorder; Brain; Brain Stem; Brain imaging; Clinical; Clinical Trials; Controlled Clinical Trials; DSM-IV; Data; Depressed mood; Diagnosis; Diagnostic; Disease; Doctor of Philosophy; Educational Curriculum; Equipment and supply inventories; FDA approved; Fluoxetine; Functional disorder; Future; Goals; Grant; Guidelines; Hamilton Rating Scale for Depression; Health; Image; Kinetics; Knowledge; Major Depressive Disorder; Manic; Measures; Mental Depression; Mentors; Mentorship; Modeling; Molecular; Mood stabilizers; Morbidity - disease rate; Neurons; Outcome; Paper; Participant; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Population; Positron-Emission Tomography; Principal Investigator; Process; Protocols documentation; Psychiatrist; Public Health; Randomized; Recording of previous events; Research; Research Domain Criteria; Research Personnel; Research Project Grants; Research Proposals; Risk; Role; Scanning; Scientist; Selective Serotonin Reuptake Inhibitor; Serotonin; Serotonin Receptor 5-HT1A; Signal Transduction; Source; Subgroup; Symptoms; Techniques; Testing; Time; Training; Work; anxiety symptoms; base; bipolar depression depressed phase; bipolar patients; clinical remission; depressed patient; design; disability; healthy volunteer; image processing; inhibitor/antagonist; neuroimaging; novel; patient oriented research; personalized medicine; radiotracer; response; serotonin receptor; single episode major depressive disorder; skills; statistics; suicidal patient; suicidal risk; tool; translational neuroscience

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.

描述（由申请人提供）：本 K23 资助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中的大脑血清素 1A 受体，以确定成像信号是否与选择性血清素受体抑制剂 (SSRI) 抗抑郁药氟西汀添加到情绪稳定剂中时的临床反应相关。与临床结果的关联可能是识别可预测临床反应的生物标志物的第一步。这一目标很重要，因为并非所有双相情感障碍患者都对 SSRI 产生反应，而且治疗存在相关风险，因此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，是十大残疾来源之一，并且与自杀风险增加有关。此外，治疗是反复试验，是一个有问题的临床过程，而且 FDA 只批准了三种用于抑郁期的药物。最近的一篇论文表明，大脑血清素 1A 受体的 PET 信号与三个月非结构化治疗后的临床缓解相关。另一篇论文表明，PET 信号与重度抑郁症中 SSRI 的临床反应相关。该研究的另一个目的是确定 PET 信号是否与双相抑郁症的焦虑或攻击性症状相关。如果存在相关性，这可能是重新定义生物血清素信号传导诊断的第一步。该项目采用了一种新型放射性示踪剂 [11C] CUMI-101，该放射性示踪剂比其他放射性示踪剂具有重大进步。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。这是一项培训补助金，该研究项目将为其首席研究员 Martin Lan（医学博士、哲学博士）提供发展成为一名 独立神经影像研究员。他之前有基础科学技术的研究背景，这笔赠款将使他获得以患者为导向的研究技能，以便在他的研究中利用他作为精神病学家的临床培训。在项目期间，他将接受该领域专家的指导，包括他的主要导师 J John Mann 博士、共同导师 R. Todd Ogden 博士、合作者 Patrick McGrath 博士和顾问 Jeffrey Meyer 博士。这种指导以及增加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和转化神经科学方面的必要技能。