Imaging of Serotonin Transporters in Depression

描述(申请人提供)：结构和功能成像研究 已经提出了一种情绪障碍的神经回路，它涉及一种 丘脑-皮质环路(杏仁核、丘脑、前额叶皮质)和 边缘-纹状体-苍白球-丘脑-皮质环路。中的异常现象 这些回路的组成部分可能会影响情绪的调节。5-羟色胺 与抑郁症的病理生理学有关。关于血小板减少的报道 严重抑郁症的5-羟色胺转运体很少延伸到 死后脑研究和活体神经感受器成像研究。5-羟色胺 SPECT检测抑郁症患者脑干转运蛋白结合 据报道，这一数字较低。[“C]McN5652是一种具有高亲和力的PET放射性配体 5-羟色胺转运体。我们的团队已经开发了动力学建模方法 这一配体允许对5-羟色胺转运体进行定量 皮质下，在一些皮质结构中程度较轻。我们提出了一个 大鼠5-羟色胺能系统神经回路的活体研究 抑郁症。我们预测抑郁症患者的转运蛋白结合量会减少 受试者在中脑、丘脑、壳核、海马体和杏仁核。 抑郁症的症状与5-羟色胺能指标有关，包括 自杀意念、精神运动迟缓和焦虑。我们将相互关联 这些精神病理学的测量与[“C]McN5652绑定。相关性将 帮助完善抑郁症的神经回路模型。有几条证据 提示抑郁症患者的5-羟色胺功能障碍可能是一种特征标记。 因此，我们将研究目前抑郁的患者(n=40)和缓解的患者 停药期间抑郁受试者(N=20)，并将两组患者与 健康志愿者(N=20)。我们预测缓解性抑郁症将与 目前抑郁的受试者。这些结果将极大地提高我们的知识 对抑郁症的病理生理学和我们的诊断有帮助， 治疗，以及未来研究的设计。这份申请是针对一位导师 临床科学家发展奖已提交，目标是 支持申请者作为精神科医生的职业发展 研究员。这项研究计划旨在建立在候选人先前的基础上 在情绪障碍中使用神经感受器成像。此应用程序描述了 神经生物学领域的培训和指导计划 抑郁症，细胞和分子生理学，药理学，神经解剖学， 统计分析、临床诊断和评级、教学、脑成像、 以及必要的数学建模，使申请者能够进行 独立从事精神病学的科学研究工作。这些目标将会实现 通过授课、课程作业和监督相结合的方式。

DESCRIPTION (Provided by Applicant): Structural and functional imaging studies have suggested a neurocircuitry of mood disorders that involves a limbicthalamic-cortical circuit (amygdala, thalamus, prefrontal cortex) and a limbic-striatal-pallidal-thalamic-cortical circuit. Abnormalities in a component of these circuits may affect the regulation of mood. Serotonin has been implicated in the pathophysiology of depression. Reports of fewer platelet serotonin transporters in major depression have rarely been extended to postmortem brain studies and neuroreceptor imaging studies in vivo. Serotonin transporter binding in the brainstem of depressed patients measured by SPECT is reportedly lower. ["C]McN5652 is a PET radioligand with high affinity for the serotonin transporter. Our group has developed kinetic modeling methods with this ligand that allow quantification of the serotonin transporter in subcortical and to a lesser extent in some cortical structures. We propose an in vivo study of the neurocircuitry of the serotonergic system in major depression. We predict that transporter binding will be decreased in depressed subjects in the midbrain, thalamus, putamen, hippocampus, and amygdala. Symptoms of depression have been correlated to serotonergic measures, including suicidal ideation, psychomotor retardation, and anxiety. We will correlate these measures of psychopathology with ["C]McN5652 binding. Correlations will help refine the neurocircuitry model of depression. Several lines of evidence suggest that serotonin dysfunction in depression may be a trait marker. Consequently, we will study both currently depressed (n=40) and remitted depressed subjects (N=20) while off medication, and compare both groups to healthy volunteers (N=20). We predict remitted depressed will not differ from currently depressed subjects. These results will greatly enhance our knowledge of the pathophysiology of major depression and help in our diagnosis, treatment, and design of future studies. This application for a Mentored Clinical Scientist Development Award has been submitted with the goal of supporting the development of the applicant's career as a psychiatric researcher. This research plan is intended to build on the candidate's prior work with neuroreceptor imaging in mood disorders. This application delineates plans for training and mentoring in the areas of the neurobiology of depression, cell and molecular physiology, pharmacology, neuroanatomy, statistical analysis, clinical diagnosis and ratings, teaching, brain imaging, and mathematical modeling necessary to enable the applicant to pursue an independent career of scientific inquiry in psychiatry. These goals will be met by a combination of didactic I course work and supervision.