抑郁症脑神经环路功能的分子遗传机制研究

项目名称： 抑郁症脑神经环路功能的分子遗传机制研究

项目编号： No.91232711

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 马小红

作者单位： 四川大学

项目金额： 60万元

中文摘要： 抑郁症是临床常见的重性精神疾病之一，其高复发率和高自杀率对患者、家庭和社会都带来极大的负担。由于遗传和环境相互作用的复杂性，抑郁症的病因至今未明。本研究以患者、亲属和健康人为研究对象，针对抑郁症临床表现异质性高这一难题，将脑影像学研究所发现的神经环路异常作为疾病的表型之一，结合患者的神经认知功能和行为特质（如自杀），初步建立抑郁症多模态生物学表型指标。选取与这些神经环路功能表现有关的基因，根据HapMap计划所公布的标签SNP，系统分析抑郁症神经环路异常的分子遗传机制，将多模态生物学表型指标作为定性和定量疾病表型进行遗传统计分析。对于前述所发现的异常遗传表现，将在独立的大样本中进行验证，以期寻找到真正与抑郁症发病相关的遗传因素。本研究将脑影像学和分子遗传学研究技术结合，是目前国际上对复杂性疾病研究常用的方法之一，在中国人群中进行的系统分析，对明确抑郁症的分子遗传病因学机制具有重要作用。

中文关键词： 抑郁症；脑影像学；分子机制；；

英文摘要： Depression is a common clinical psychotic disease, its high recurrence rate and high suicide rate have caused great burden on patients, families and society. Due to the complex interaction of genetic and environmental factors, the etiology of depression is not so clear till now. This study will recruit patients with depression, patients’ relatives and healthy subjects. The difficulty in this study is that clinical manifestation of depression has high heterogeneity. We will use neural circuitry abnormalities which were found in brain imaging studies as the disease phenotype. Combined with neurocognitive and behavioral characteristics ( such as suicide behaviour), we will develop an initial multiple modal biological phenotypes of depression. For the genetic study, the related genes to the neural circuit function expression will be selected and all tagSNPs according to HapMap plan will be analyzed. We are going to explore the molecular genetic mechanisms of neural circuitry abnormalities in depression. The multi-modal biology phenotypes will be used as qualitative and quantitative disease traits in genetic statistical analysis. The abnormal genetic traints found in this study will be extend tested in the independent sample with relatively large sample size in order to find the real genetic factors associated with d

英文关键词： depression；brain image；molecular genetics；；