Imaging of Serotonin Transporters in Depression

描述（由申请人提供）：结构和功能成像研究 提出了情绪障碍的神经回路， 边缘丘脑-皮层回路（杏仁核、丘脑、前额叶皮层）和 边缘纹状体苍白球丘脑皮质回路中的异常的 这些回路的组成部分可能会影响情绪的调节。血清素具有 与抑郁症的病理生理有关报告血小板减少 抑郁症中的5-羟色胺转运体很少被扩展到 死后脑研究和体内神经受体成像研究。血清素 通过SPECT测量抑郁症患者脑干中的转运蛋白结合， 据报道，更低。McN 5652是一种PET放射性配体，对靶细胞具有高亲和力。 血清素转运体我们的团队已经开发了动力学建模方法， 这种配体可以定量血清素转运蛋白， 在皮质下，在某些皮质结构中程度较轻。我们提出了一个 在体内研究的神经元能系统的神经回路的主要 萧条我们预测，在抑郁症患者中， 中脑、丘脑、壳核、海马体和杏仁核。 抑郁症的症状与肾上腺素能指标相关，包括 自杀意念、精神发育迟滞和焦虑。我们将把 这些精神病理学指标与McN 5652结合。相关性将 帮助完善抑郁症的神经回路模型。若干条证据 表明抑郁症中血清素功能障碍可能是一个特征标记。 因此，我们将研究目前抑郁（n=40）和缓解 抑郁受试者（N=20），而停药，并比较两组， 健康志愿者（N=20）。我们预测缓解抑郁症不会有什么不同， 目前抑郁症患者。这些结果将大大增进我们的知识 重度抑郁症的病理生理学，并帮助我们诊断， 治疗和未来研究的设计。这份申请表 临床科学家发展奖已提交的目标是 支持申请人作为精神科医生的职业发展 研究员本研究计划旨在建立在候选人的先验 神经感受器成像在情绪障碍中的应用本申请描述了 在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， 和数学建模，使申请人能够追求一个 独立从事精神病学的科学研究。这些目标将得到实现 通过教学和监督相结合。

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.