Major depressive disorder(MDD) is a common mental disorder that influenced by both environmental factors and genetic factors.Environmental factors may affect MDD through disturbing expression level of specfic genes and then inducing abnomal mental and behavior. The confused gene expression is regulated by a series of molecular processes that construct a regulatory network of MDD. Researching this network systematically will advance our understanding of biological mechanism of MDD and futhure advance the identification, prevention and treatment of MDD.This project expose BALB/c mice to the chronic mild stress paradigm(CMS,an animal model of depressive) to research gene expression regulatory network that affected by MDD related environmental factors.We will analyze more than 1 000 genes that show different expression levels after CMS(reported by published literature). By using bioinfomatic methods(such as transcription factor binding site prediction,CpG island analysis, microRNA target analysis and pathway analysis) and high-throughput molecular biological experiments, a CMS drived gene expression regulatory network will be built. By constructing and analyzing this network, we propose to explain biological mechanism of environmental-genetic interplay in MDD.
重症抑郁症是一种发病率较高的精神障碍，其发生发展受相关环境与遗传因素交互作用的影响。该作用的可能模式之一是环境因素通过影响基因表达调控机制扰乱特定基因的表达，进而出现病理现象。此过程中涉及的基因表达调控网络环节众多，对该网络的系统研究将促进对重症抑郁症生物学机制的理解，进而促进重症抑郁症早期鉴别、预防以及治疗措施的研究制定。本项目通过生物信息学方法及分子生物学方法，构建慢性应激环境下小鼠前额皮质基因表达调控网络，并分析这一网络在特定环境下的动态变化，为进一步研究重症抑郁症发生发展过程中环境与基因的交互作用（genetic X environment interaction）打下坚实基础。课题整体完成顺利，在项目初始规划基础上，网络分析的研究对象自重症抑郁症拓展到双极性情感障碍，阿尔茨海默症等其他应激相关疾病，同时所关注的动物模型也从小鼠拓展到大鼠。此外，在调控网络的构建中还延展性的开展了调控分析工具的开发研究。现在基于本课题的工作有五篇SCI文章发表。
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