5-羟色胺受体系统参与脑代谢网络影响抑郁症复发的机制硏究

More than half of the patients with recurrent depression. There are no effective objective indicators for predicting recurrence for now. Serotonin system with the default mode network, salience network and cognitive control network in Depression are to play an important role in the development. But the current magnetic resonance studies of network tend to inconsistent results resting state and task state. Thus, it remains unclear of the role of these networks in depression. Abnormality of serotonin system is not directly used as an indicator of recurrence. Our preliminary work revealed that glucose metabolism, as one of the important ways to measure brain function can prove that the three networks involved in the depression. Besides, we indicated depression patient’s glucose metabolism brain network anomalies compared with controls. We will use 18F-FDG and 18F-MPPF5 serotonin receptor PET scans to analysis the three brain networks and to observe neurotransmitter receptors. Our study is of great significance to identity the different pattern of the onset and recurrence patients with brain dysfunction and mechanism. The study findings will help to provide new ideas for imaging biomarkers of depressive disorder recurrence by identifying for the pattern of recurrent patients.

半数以上的抑郁症患者出现复发，目前还无有效的客观指标来预判复发。5-羟色胺系统与默认网络、凸显网络和中央执行网络功能在抑郁症的发生发展过程中都着起重要作用。但是目前磁共振的网络研究往往出现静息态与任务态结果不一致的情况，从而不能明确这些网络在抑郁症中的作用。5-羟色胺系统的异常表现又不能直接作为复发的指标。我们前期工作发现葡萄糖代谢作为衡量脑功能的重要手段可以证明三大网络参与到抑郁症中。并且我们证明了抑郁症患者与正常人相比葡萄糖糖代谢全脑网络出现异常。我们将用18F-FDG及18F-MPPF5-羟色胺受体PET显像进行三大脑网络分析及递质受体的研究，探索首发与复发患者的脑功能异常及其疾病基础。寻找复发患者的特征性表现，为寻找判断抑郁症复发的影像学生物指标提供思路。

根据抑郁症患者以及正常对照的基线期多模态 PET（包括以葡萄糖代谢、5-羟色胺为靶点的 PET 显像和功能磁共振显像）和 MRI 数据，完成抑郁症患者相关脑代谢模式的建立和5-羟色胺特征的提取。我们发现抑郁症患者的壳核、屏状核、岛叶、额下回、缘上回葡萄糖代谢较正常对照组减低。并且根据功能静息态功能磁共振的研究结果发现葡萄糖代谢减少的脑区与功能连通性受损的脑区具有一定的相关性，如额下回、角回、距状沟、额中回。这些的关键脑区主要位于背外侧前额叶皮层(DLPFC)/顶叶、突显网络(SN)，它们分别是初级视觉皮层(V1)和语言网络的关键枢纽，是作为抑郁症发病机制和诊疗指导的重要靶点。继而，通过对帕金森病伴抑郁患者DBS治疗队列前后多模态影像学比较研究发现，其与抑郁症相似部分脑区异常表现，并且这些脑区在经过DBS治疗后得到了好转。提示DBS对这个环路有调节作用。将来有可能将该研究成果推广到DBS治疗难治性抑郁症患者，协助临床探索难治性抑郁症的诊疗新技术。