TNF-α基因多态性调节抑郁障碍认知功能损害的脑网络机制研究

项目名称： TNF-α基因多态性调节抑郁障碍认知功能损害的脑网络机制研究

项目编号： No.91232719

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： 方贻儒

作者单位： 上海市精神卫生中心

项目金额： 70万元

中文摘要： 认知功能损害是抑郁障碍三大临床症状群之一，影响患者社会功能和疾病预后。课题组前期研究发现，抑郁障碍存在工作记忆损害；全基因组表达谱芯片筛查则见细胞因子-细胞因子通路在抑郁障碍中存在显著差异表达，尤以TNF-α基因的差异最为显著。由此假设TNF-α基因多态性通过影响TNF基因的转录活性调节TNF水平，损害海马及其相关记忆环路神经元的可塑性和认知过程中的工作记忆水平，阻碍MDD患者社会功能恢复。本课题将应用成套神经心理测试工具以及基于MRI的多模态脑影像学技术和分子影像学方法进一步探索TNF-α基因多态性对情绪与认知功能影响的脑网络依赖效应，比较TNF不同基因型对于工作记忆和海马相关记忆环路的影响；应用不同机制抗抑郁药物验证TNF-α与抑郁障碍认知功能脑网络的联系。预期将会对工作记忆损害是否为抑郁障碍的内表型提供参考依据，为TNF-α介导的抑郁障碍认知功能损害的脑网络依赖效应提出理论假设。

中文关键词： 抑郁障碍；TNF；工作记忆；MRI；海马

英文摘要： Cognitive function impairments, which influence rehabilitation of social function and disease prognosis, is one of the three major clinical syndromes in major depressive disorder (MDD). But unfortunately, this was still poorly understood in clinical practice up to now. Our previous studies found that, cognitive function impairments do exist in patients with MDD. On the other side, cytokines-cytokines pathways in MDD were significantly differentially expressed, especially the TNF-α gene. Thus, we suppose that TNF-α gene polymorphism may influence TNF gene transcription activities and regulate the level of TNF. High TNF level may damage the neuronal plasticity in central nervous system, so as to impair working memory and hinder the recovery of social function in patients with MDD. In current study, neuropsychological test battery, MRI based multi-modality brain image technology and molecularimaging will be used to further explore the impacts of TNF-α gene polymorphism on mood and cognitive function in brain, and to compare the impacts of different TNF genotypes on working memory and hippocampal related memory circuits. Different pharmacological mechanism antidepressants will be used to treat the patients with MDD in current study to verify the relationship between TNF-α and cognitive function of brain network link

英文关键词： major depressive disorder；TNF；working memory；MRI；hippocampus