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。本项目选取慢性温和应激范式这一较成熟的抑郁症动物模型，构建该环境中小鼠全脑基因表达调控网络并进行生物学分析。项目将从文献报道在这一环境中存在差异表达的千余基因入手，通过转录因子结合位点分析、CpG岛分析、小RNA靶点分析、生物学通路分析等生物信息学手段构建与此环境相关的表达调控框架，并就其中的关键环节如热点基因的表达水平、热点转录因子活性等进行高通量分子生物学实验研究，最终构建受CMS环境驱动的表达调控网络，解释重症抑郁症中环境与遗传因素交互作用的部分生物学机制。

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.