Genes and Alterations in Brain Structure and Function in Depression

描述(申请人提供)：越来越多的研究支持遗传对大脑结构和功能的影响。这项工作的大部分都是在健康成年人身上完成的。与此同时，对可能使个人易患抑郁症的遗传因素也进行了大量调查。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，但调查这些多态是否对抑郁症成年人有不同影响的研究有限。本研究将考察两种基因多态对脑结构和神经认知功能的影响。这些多态与健康个体大脑结构和功能的改变有关，并可能成为抑郁症的易感基因。假设：5-羟色胺转运体启动子区和儿茶酚-O-甲基转移酶Val158met多态的短等位基因将分别与120名复发性抑郁症成年人和120名没有精神疾病的成年人的脑结构和神经认知功能的改变有关。作为一个探索性假设，我们将检验基因对大脑结构和功能的影响，这可能是抑郁症患者特有的。方法：这是一项横断面研究，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集中在与这些基因多态相关的区域：杏仁核、海马体和背外侧前额叶皮质。将使用体积张量和扩散张量图像分析方法。相关性：这项研究阐述了NIMH更好地了解抑郁症潜在的病理生理学的使命，使用转化性研究来整合跨科学学科的方法。它与公共卫生问题有关，因为抑郁症是一个常见的问题，其病理生理学基础知之甚少。该项目将提供有关遗传因素如何影响大脑以及复发性抑郁症患者的不同之处的信息。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。项目说明： 该项目将研究两个基因，一个与5-羟色胺有关，另一个与多巴胺有关，以及它们对患有和不患有抑郁症的人的大脑结构和功能的影响。更好地了解基因如何影响大脑是至关重要的，因为我们更好地了解抑郁症，这是一种严重的疾病，会导致严重的残疾和死亡。这项研究将促进我们对基因如何影响大脑的理解，这反过来将为抑郁症的原因提供重要信息。

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.