抑郁症是当今世界发病率最高的脑部精神疾病之一，也是当今社会导致自杀的主要原因。目前抑郁症的发病机制仍不明确。全基因组高通量测序分析抑郁症病人并没有发现有效的易感基因信息。抑郁症的诊断仅仅依靠“问卷调查” 手段，尚未有客观的影像和生化标记物。我们在前期工作中开发了基于整合串联质谱和磁共振波谱法分析的新一代靶向代谢组学方法。我们前期研究还发现抑郁症模型大鼠海马和血液代谢与正常组之间具有显著差异。据此，我们提出了抑郁症的本质可能是一种脑功能、脑连接和脑代谢异常的代谢疾病的假说。本课题拟在前期工作基础上，建立慢性应激抑郁症大鼠模型。运用新一代靶向代谢组学技术、磁共振波谱和静息态功能磁共振成像对模型易感脑区从脑代谢和脑功能连接两个方面进行深入系统研究。本研究旨在揭示抑郁症脑代谢和脑连接异常机理，发现早期诊断抑郁症的影像和生化标记物，为抑郁症的早期诊断提供科学依据。

Major depression disorder is one of the most common mental diseases and the leading cause for suicide. So far, the pathological mechanisms of depression are still not clear. Whole genome sequencing failed to identify useful genetic factors in the patients with depression. The current diagnosis of depression is mainly based on “questionnaire”. There is still lack of objective neuroimaging and biochemical markers for depression. In our previous studies, we established the next-generation targeted metabolomic approach based on the integration of LC-MS/MS and 1HMRS. We also showed that there was a significant difference on the hippocampal metabolism between the depression-like rats and controls. Therefore, we hypothesized that depression is a metabolic disorder caused by the abnormal metabolism and connectivity in brain. The objective of this study is to investigate the abnormal connectivity and metabolism in the susceptible brain regions of depression. We will first generate a chronic mild stress model of depression in rats. The metabolism, function and fiber connection of susceptible brain regions will then be systematically studied using next-generation targeted metabolomics, 1H-MRS and resting state fMRI. In summary, our study will provide a scientific basis for the early diagnosis of depression.