抑郁症自杀未遂者Gamma神经振荡动态谐振网络的脑磁源性影像研究

Suicide attempts in depression has serious harmfulness. In research fields, the neuropathological basis has been concerned and explored from the perspective of neuropsychology, molecular biological or neuroimaging techniques. GABAergic interneurons play a key role as generators and regulators of gamma oscillatory activity which can be detected from cellular design to macrocircuit function. Recently, It is the focus of studies in the pathological mechanism of suicide attemts in depression. The previous researches using magnetic resonance imaging (MRI) have found that the prefontal -striatal-temporal circuit has relationship with suicide idea in depression. The changes of brain activity in region extent, location and functional connection were characteristics and havecorrelation with clinical symptoms. However, instant functional changes of neural activity were related to mental disorder states, and even in the early stage of the illness detection. As the limitations of temporal and spatial resolutions, it is impossible to distinguish the order of instant neural activation. And there are no literature regarding it. The project will combine the MRI and Magnetoencephalography (MEG) to procure the magnetic source imaging (MSI) with high spatial and temporal resolutions. The tasks of this project include: to locate and verify the pathological circuit of suicide idea accurately, to discuss the spatial-temporal pattern and the biological neuroimaging features of the circuit; in addition, to observe the dynamic synchronous network of gamma rhythm activity of the loop in depressive patients with suicide attempts and discuss the further mechanism of suicide ideas in depression. The project is a study with original innovation, and it will be beneficial in providing facilitation for further researches on the pathogenesis of depression.

抑郁症自杀危害严重，其神经病理基础一直为研究者所关注，并从神经心理学、分子生物学或影像学等角度深入探讨。GABA中间型神经元是产生和调节gamma神经节律振荡的基础，能从微观到宏观不同尺度上评测，在抑郁症自杀病理研究中引起高度关注。前期磁共振（MRI）研究发现：与抑郁症自杀相关的“前额叶-纹状体-颞叶”环路改变，其在异常程度、范围和功能连接等方面有较为特征的变化。而瞬时脑动态神经振荡的谐振网络变化可能与疾病状态密切相关。但受时间分辨率限制，MRI研究未能准确测定，也未见其他文献报道。因此，本项目旨在发挥脑磁图（MEG）高时间分辨率的优点，结合高空间分辨率MRI形成磁源性影像（MSI），对抑郁症自杀相关的神经环路进行验证和精确定位，探讨其时空模式特性；通过对该环路gamma神经振荡动态谐振网络的研究，寻找与自杀相关的生物信息学标记。本研究具有源头创新性，可为深入探讨抑郁症病理机制提供帮助。

抑郁症与自杀密切相关，约 65%的抑郁症患者有自杀意念，60%的自杀者被诊断为抑郁症，抑郁症自杀危害严重，但是目前抑郁症自杀的发病机制仍不清晰。既往研究发现Gamma节律的产生与抑郁症自杀行为，自杀意念的抑郁症患者可能表现为“前额叶-纹状体-颞叶”环路的异常。本课题首先利用静息态功能磁共振技术对伴自杀抑郁患者进行研究，然后在此基础上使用磁源性影像技术进行验证及进一步探索。在伴自杀的抑郁患者研究发现前额叶边缘系统静息态功能磁共振存在异常。通过脑磁源性影像交叉频率耦合（CFC）测量α波段（8–13 Hz）调制皮质γ波段（30～48赫兹）。研究发现，右尾状核之间的α-γ相位振幅耦合（pac）显著降低。与低危险自杀组和健康对照组相比，高危自杀组的左丘脑较低，右尾状核和左丘脑之间耦合较弱，表明抑郁症自杀者的尾状核异常。围绕与自杀相关脑区主要与背外侧前额叶皮质（DLPFC）、尾状核和丘脑，所形成皮质-纹状体-丘脑皮质（CSTC）神经环路，发现CSTC回路的紊乱导致MDD患者自杀风险增加。通过动态拓扑验证了该分类算法在低γ波段的性能单个模式的特征。与α带和β带相比，在低频γ条件下，个体时空图的最佳鉴别准确率为91.01%。.本项目完成了研究计划制定的全部内容，发表论文41篇，其中SCI/SSCI 22篇，EI 3篇，影响因子总分71.827分，发表国际国内会议摘要73篇，获得江苏省新技术引进奖一等奖，江苏省科教强卫工程省市共建医学创新团队，项目主持人获江苏省第五期“333高层次人才培养工程”第二层中青年领军人才。本项目培养博士后2名，其中出站1人；培养博士研究生4名，毕业1人；培养硕士研究生4名，全部顺利毕业；继续加强研究团队建设。本研究具有源头创新性，探讨抑郁症自杀的生物学基础及与临床预后的关联性，并将基础研究的成果转化成实际为患者提供的诊断方法，从实验室到临床，做到更精确的预警与诊断、从而更及时的干预和治疗。