Conte Centers for the Neuroscience of Depression

整体中心描述(由申请人提供)：建议的Silvio O。 康特抑郁症神经科学中心将专注于了解 抑郁症的神经生物学机制。我们将用自然产生的 皮损可作为老年抑郁症的典范。我们将使用损伤入路来 研究情绪回路和情绪调节。共有5个项目是 建议。第一个检查病变的定位，结构变化 辅助回路的关键区域和脑白质的改变 与赛道相关的区域。第二个项目使用的是尸检细胞 计数和神经胶质体积评估以评估相关区域的变化。 第三个项目使用认知范式和功能磁共振来探索 巡回赛。第四个项目使用转基因和基因敲除小鼠来检查 去甲肾上腺素和5-羟色胺在环路中的作用。决赛 该项目旨在评估去甲肾上腺素对人体的影响 缓解性抑郁症皮损患者5-羟色胺耗竭的评估 这些神经递质作为一种机制的重要性。三个共享资源， 行政、研究和评估以及数据管理/统计 提议为这些项目的实施提供便利，并确保一体化 在概念、分析和患者可获得性级别，并流向 各种各样的项目。该中心的发现应该会极大地增强我们的 了解抑郁症的生物学，但也可能有所帮助 在改善这些疾病的治疗方面。此外，技术上的 在该项目的背景下开发的创新可能具有重大意义 对脑功能的其他研究具有重要意义和相关性。

DESCRIPTION OF OVERALL CENTER (provided by applicant): The proposed Silvio O. Conte Center for Neuroscience of Depression will focus on understanding the neurobiological mechanism of depression. We will use the naturally occurring lesions in the elderly depressed as a model. We will use a lesion approach to study the mood circuit and affect regulation. A total of 5 projects are proposed. The first examines localization of lesions, structural changes in critical regions subserving the circuit and alterations in the white matter tracts relevant to the circuit. The second project uses post mortem cell counting and glial volume assessment to assess changes in the relevant region. The third project uses cognitive paradigms and functional MRI to probe the circuit. The fourth project uses transgenic and knockout mice to examine the role of norepinephrine and serotonin as it relates to the circuit. The final project is designed to assess in humans the impact of norepinephrine and serotonin depletion in remitted depressed patients with lesions to evaluate the importance of these neurotransmitters as a mechanism. Three shared resources, administrative, research, and assessment and data management/statistics are proposed to facilitate the conduct of these projects and to ensure integration at the conceptual, analytical and patient availability level, and flow to the various projects. Findings from the center should greatly enhance our understanding of the biology of depressive disorders, but may also be of help in improving the treatment of these disorders. In addition, the technological innovations developed in the context of this project are likely to be of major importance and relevant to other studies of brain function.