基于DRD2基因的创伤后应激障碍影像遗传学研究

The abnormalities of brain structure and function may play an important role in the pathological mechanism of post-traumatic stress disorder (PTSD), and the genetic background of these anomalies is not clear. One of the obstacles encountered is that PTSD have also been confounded by psychiatric comorbidity, most particularly depression, and traditional behavioral measurement may cover up the potential impact of gene due to subjective factors. Based on the constructed psychological crisis intervention and service network in Hainan province, we choose PTSD patients with and without comorbid of depression and healthy controls, all participants will have brain structure (VBM-based 3D brain structures, DTI) and resting state functional magnetic resonance examination (amplitude of low frequency fluctuation and intrinsic connectivity network analysis). Take these abnormalities of brain structure and function as endophenotypes, relational analysis with the dopamine D2 receptor (DRD2) gene polymorphism. The objective of this study is to investigate the similarities and differences of altered brain structure and function characteristics in PTSD with and without comorbid of depression;to investigate susceptibility gene specific regulation on brain structure, function of PTSD. We will initially establish the corresponding relationship from the DRD2 of different genotype to specific brain structure, function model and behavior level; and then screen early PTSD-specific imaging genetics target.This project can provides new scientific evidence for partly understanding the molecular mechanism of PTSD and PTSD comorbidity.

创伤后应激障碍（PTSD）患者有不同程度的脑结构、功能的病理性损害，而遗传背景对这些异常的影响尚不明确，其障碍之一是PTSD常有抑郁等共病干扰，而传统的行为学测量受主观影响、常会掩盖潜在的基因影响。本研究在前期已构建的海南省心理危机干预及服务网络基础上，选择单纯PTSD、PTSD共病抑郁及正常对照者，以脑结构（基于VBM的3D脑结构分析、DTI）、静息态功能磁共振为内表型，与多巴胺D2受体（DRD2）单核苷酸多态性（SNPs）进行关联分析。目的在于探讨PTSD与PTSD共病抑郁患者脑结构、功能改变共性与差异；考察易感基因DRD2对PTSD特定脑结构、功能的调控作用，初步建立从DRD2不同基因型到特定脑结构、功能模式及行为水平的对应关系；进而筛选PTSD特异的影像遗传学早期识别靶标，本项目可一定程度上为理解PTSD及其共病的分子机制提供新的科学证据。

创伤后应激障碍（post-traumatic stress disorder，PTSD）是由军事战争、自然灾害、交通事故等创伤事件引起的一种常见精神疾病。临床上，PTSD以创伤经历再体验、回避、负性的情绪和认知、高警觉性等四大症状群为特征。尽管PTSD症状严重影响了患者的生活质量，目前该疾病的神经学基础尚未完全阐明。本研究采用静息态功能磁共振技术（分别从杏仁核的功能连接和效应连接、静息态网络内和网络间连接、大尺度功能连接网络的角度）及全基因组关联分析对威马逊台风经历者及未经历台风正常人的脑功能及遗传学数据进行了分析比较，发现PTSD及创伤均可引起杏仁核功能连接、效应连接、静息态脑网络及全脑功能连接网络的功能改变。结果表明除默认网络、执行控制网络及突显网络的异常外，PTSD患者还存在感觉运动网络的脑功能改变。具体来讲，内侧前额叶对杏仁核的较强抑制作用、海马与中央后回间较强功能连接及较高的壳核节点连接强度代表较强的情绪调控、信息整合及奖赏加工能力，是PTSD发病的保护因素。楔前叶的功能改变具有相对PTSD相对特异性，可能与PTSD患者的自我参照加工受损有关。创伤可导致颞上回及岛叶等脑区的功能连接改变，但PTSD可能促进创伤引起的脑功能损害。基因分析发现DRD2 中位于PTSD组的rs521861位点的基因型CG、G、C与创伤对照和健康对照组比较均有明显差异（P<0.01），提示rs521861在PTSD的发生中可能发挥了重要作用。上述发现可能揭示了创伤后应激障碍的病理基础并为其早期干预保护、预后评估提供无创、定量手段。