基于影像遗传学的抑郁症自杀行为早期预测及其机制研究

Depression not only affects the individual's physical and mental health, social function, but also has a high suicide risk. Suicidal behavior in depression and its molecular mechanism has not yet been fully elucidated. Abnormalities of brain structure and function play an important role in the pathological mechanism, and the genetic background of these anomalies and its impact so far is not clear. Participants were 100 depression patients with suicidal behavior, severe depression without suicidal behavior patients ,100 healthy comparison subjects matched for age, gender, education, and ethnicity. The brain structure and resting functional magnetic resonance imaging in a 3.0 Tesla magnetic resonance scanner was performed, and the TPH2 gene polymorphism be analyzed respectively. Wholebrain voxel-based analysis was used to compare brain structure across the three groups, Reho and alff analysis were used to compare the brain function across the three groups, and analyze the correlation with TPH2 SNPs. The aim is to explore the characteristics of depression with suicidal behavior of brain structure and function; study the impact of THP2 gene polymorphisms on suicidal behavior; examine the susceptibility genes the regulatory role of specific brain structure and brain function, preliminary built from different genotypes to specific brain structures functional model and the corresponding suicidal risk relationship, then screening for depression suicidal risk imaging and gene early predictive indexes, for subsequent long-term follow-up study for neural network dynamic variation and gene imaging efficacy markers to lay the foundation.

抑郁症不仅影响着个体的身心健康、社会功能，而且有很高的自杀风险。抑郁症自杀行为其分子机制仍未完全阐明，大脑结构及功能的异常在其病理机制中起到重要作用，而遗传背景对这些异常的影响迄今尚不明确。本研究选择抑郁症自杀未遂者、重症抑郁症无自杀行为者及正常对照者，分别进行脑结构、静息态功能磁共振扫描和TPH2基因多态性分析。目的在于探讨抑郁症自杀行为者脑结构及功能改变特征；研究TPH2基因多态性对自杀行为的影响；考察抑郁症自杀行为易感基因对特定脑结构与脑功能的调控作用，初步建立从不同基因型到特定脑结构、功能模式及相应抑郁症自杀行为的对应关系；进而筛选抑郁症自杀风险的影像遗传学早期预测指标，为后续长期随访研究寻找神经网络动态变化特征以及基因-影像疗效标志奠定基础。

抑郁症不仅影响着个体的身心健康、社会功能，而且有很高的自杀风险。大脑功能的异常在抑郁症自杀行为病理机制中起到重要作用，但其对自杀行为的影响尚不明确。本研究选择抑郁症自杀未遂者(DES)、抑郁症无自杀行为者(DEN)及正常对照者(HC)，进行3D脑结构、静息态脑功能磁共振分析及TPH2候选基因多态性分析，探讨抑郁症自杀行为者脑结构、功能及基因改变特征。研究发现ALFF与ReHo两种不同原理的数据分析方法得到DES患者基本一致的脑功能改变空间分布模式：功能升高的区域主要位于背外侧前额叶、边缘系统及右侧尾状核，功能降低的脑区包括枕叶皮层、中央后回。额前-纹状体网络与自杀行为显著相关，右侧尾状核和左侧中央后回脑功能改变有可能作为抑郁症自杀严重程度评价的潜在生物学标记。基于VBM的脑结构分析显示，前额叶、颞叶及边缘系统脑灰质体积降低与抑郁症自杀行为相关，相关脑结构改变可能是抑郁症自杀行为发生的脑结构基础。这些基于无创影像学方法的发现，为抑郁症自杀的早期干预、治疗和预后评估提供了可能的科学依据。同时，THP2的基因多态性分析结果显示，与HC组比较，DES组rs5799061位点的基因型TT和等位基因DEL、T.DEL与抑郁症自杀行为有关，但该位点作为抑郁症自杀倾向的证据尚且还有争议，未来需要更大样本的进一步分析验证其可靠性。该项目共发表相关论文12篇，其中SCI7篇，中华系列论文3篇。