Conte Centers for the Neuroscience of Depression

总体中心描述（由申请人提供）：拟建的Silvio O. Conte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使用自然发生的 以老年抑郁症病变为模型。我们将采用损伤入路， 研究情绪回路和情绪调节共有5个项目 提出了第一种检查病变的定位， 辅助回路的关键区域和白色物质的改变 与电路相关的电路。第二个项目使用死后细胞 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成像来探讨 电路.第四个项目使用转基因和基因敲除小鼠来检查 去甲肾上腺素和血清素的作用，因为它涉及到电路。最终 该项目旨在评估人体去甲肾上腺素的影响， 5-羟色胺耗竭缓解的抑郁症患者的病变，以评估 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、评估和数据管理/统计是 为促进这些项目的实施并确保一体化， 在概念、分析和患者可用性层面， 各种项目。该中心的研究结果将大大提高我们的 了解抑郁症的生物学，但也可能有帮助 改善这些疾病的治疗。此外，技术 在这个项目的背景下开发的创新可能是主要的 重要性和相关的其他研究大脑功能。

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.