Genes and Alterations in Brain Structure and Function in Depression

描述（由申请人提供）：越来越多的研究支持基因对大脑结构和功能的影响。大部分研究都是在健康的成年人身上进行的。与此同时，也有大量的研究表明，遗传因素可能使个体易患抑郁症。尽管我们对可能影响健康成年人大脑结构和功能的遗传因素的了解越来越多，但关于这些多态性是否对抑郁症成年人有不同影响的研究有限。本研究将探讨两种基因多态性对大脑结构和神经认知功能的影响。这些多态性与健康个体大脑结构和功能的改变有关，可能是抑郁症的易感基因。假设：在120名复发性重度抑郁症和120名无精神疾病的成年人中，血清素转运子启动子区域的短等位基因和儿茶酚- o -甲基转移酶val158met多态性将分别与大脑结构和神经认知功能的改变有关。作为一种探索性假设，我们将研究基因对抑郁症患者大脑结构和功能的影响。方法：这是一项横断面研究，其中受试者将完成脑磁共振成像，神经认知测试，并提供血清基因样本。图像分析和神经认知测试将重点关注与这些基因多态性相关的区域：杏仁核、海马体和背外侧前额皮质。将使用体积和扩散张量图像分析方法。相关性：本研究解决了NIMH的使命，即更好地理解抑郁症的潜在病理生理学，利用转化研究结合跨学科的方法。鉴于抑郁症是一种常见问题，其病理生理基础尚不清楚，因此与公共卫生问题相关。该项目将提供遗传因素如何影响大脑的信息，以及这对复发性抑郁症患者有何不同。更好地识别这些差异将进一步加深我们对抑郁症病理生理学的理解，从而开发出更有针对性的治疗方法。项目概述:

DESCRIPTION (provided by applicant): A growing body of research supports genetic influences on brain structure and function. Much of this work has been done in healthy adults. In parallel, there has been substantial investigation into genetic factors that may predispose individuals to the development of depression. Despite our growing understanding of genetic factors that may affect brain structure and function in healthy adults, there is limited research investigating whether these polymorphisms have a differential effect in depressed adults. The present study will examine the influence two genetic polymorphisms on brain structure and neurocognitive function. These polymorphisms have been implicated in alterations in brain structure and function in healthy individuals and may serve as susceptibility genes for depression. Hypotheses: The short allele of the serotonin transporter promoter region and the catechol-O-methyltransferase val158met polymorphism will each be associated with alterations in brain structure and neurocognitive function in a cohort of 120 adults with recurrent Major Depressive Disorder and 120 adults with no psychiatric illness. As an exploratory hypothesis, we will examine genetic influences on brain structure and function that may be specific to the depressed cohort. Methods: This is a cross-sectional study wherein subjects will complete brain magnetic resonance imaging, neurocognitive testing, and provide a serum genetic sample. Image analysis and neurocognitive testing will focus on regions shown to be associated with these genetic polymorphisms: the amygdala, hippocampus, and dorsolateral prefrontal cortex. Both volumetric and diffusion tensor image analysis methods will be used. Relevance: This study addresses NIMH's mission of better understanding the underlying pathophysiology of depression, using translational research to incorporate methods across scientific disciplines. It is relevant to public health concerns given that depression is a common problem and its pathophysiological basis is poorly understood. The project will provide information on how genetic factors affect the brain and how this may differ for individuals with recurrent depression. A better identification of these differences will further our understanding of the pathophysiology of depression, allowing the development of more focused treatments.Project Narrative: This project will examine two genes, one involved with serotonin and the other with dopamine, and their effect on brain structure and function on people with and without depression. A better understanding of how genes affect the brain is critical as we better understand depression, a serious illness which results in significant disability and mortality. This study will advance our understanding of how genes affect the brain, which in turn will provide important information on the causes of depression.