健康与遗传心理学研究室知识库

创伤后应激障碍(Posttraumatic stress disorder, PTSD)是个体暴露于重大的威胁性或灾难性应激事件后所出现的一种持续的严重的心理疾患，遗传易感性和环境因素在其发病机制中起重要作用。近年来，来自人类和动物的研究己初步证明，内源性大麻素及其受体通路可能是个体经历创伤事件后所出现的异常心理与生物应激反应的重要媒介，影响PTSD的发生发展过程，但是目前尚无研究系统而深入地探讨二者之间的关系。本研究从遗传与环境交互作用的视角出发，考察内源性大麻素受体基因((CNR1, rs806377位点)多态性及其与创伤暴露的交互作用和PTSD的发病及病情进展之间的关系，并探讨该关系背后可能的神经机制，从而系统探究内源性大麻素及其受体系统在PTSD发生发展中的作用。

本论文共包含三个研究。第一个研究旨在考察内源性大麻素受体基因多态性与PTSD总体症状及其各症状簇之间的关系。结果表明，在地震幸存者群体中，内源性大麻素受体基因多态性与创伤暴露的交互作用可以显著预测PTSD快感缺失症状簇。第二个研究旨在大脑结构的水平上探讨这一关系的神经机制。结果表明，在控制了创伤暴露水平之后，内源性大麻素受体基因型与PTSD组别在右侧眶额叶内侧皮层表面积、右侧眶额叶外侧皮层厚度、右侧额上回皮层表面积上具有显著交互作用。第三个研究使用潜类别混合模型(LGMM)纵向考察了内源性大麻素受体基因多态性与创伤暴露的交互作用和PTSD发展变化轨迹之间的关系。结果发现，在青少年群体中，PTSD的发展轨迹呈现三个组别，分别为低症状缓解组、中等症状持续组和高症状持续组，而内源性大麻素受体基因多态性与创伤暴露的交互作用可以显著预测这三个组别的分类。

总体来说，本研究发现，内源性大麻素受体基因多态性与创伤暴露的交互作用可以显著预测PTSD快感缺失症状簇的严重程度，右侧眶额叶和右侧额上回的灰质皮层结构损伤可能是这一关系的神经基础。此外，内源性大麻素受体基因多态性与创伤暴露的交互作用还可以显著预测PTSD的发展变化轨迹。本研究的一系列发现为证实内源性大麻素及其受体系统在PTSD的发生发展中的重要作用提供了证据，也有助于促进对PTSD病因和发病机制的理解，为未来PTSD的精确诊断与干预提供可能的生物标记与靶点。

Posttraumatic stress disorder (PTSD) is a complex and severe mental disorder triggered by exposure to an extraordinarily traumatic event. Many studies provided evidence supporting a genetic predisposition to PTSD. Human and animal studies suggest that the endocannabinoid receptor system may be an important mediators of abnormal stress responses following exposure to traumatic events, which implicates an important role of this system in the development of PTSD. This have dissertation focused on the associations between the endocannabinoid receptor gene (CNR 1，rs806377 genotype) x trauma exposure interaction and PTSD, and aimed to systematically investigate the role of the endocannabinoid receptor system in the occurrence and development of PTSD.

The studies were comprised of three sections. Section 1 investigated the associations between the CNRl genotype x trauma exposure interaction and PTSD symptoms. The results showed that the interaction was only associated with severity of the anhedonia symptom. Section 2 investigated the brain mechanism of that association above-mentioned. The results showed that CNRl genotype x PTSD group interaction was associated with the cerebral morphological abnormalities of the right orbitofrontal cortex (OFC) and the right superior frontal gyrus (SFG) . Section 3 intended to verify the relationships between the CNRl genotype x trauma exposure interaction and the trajectories of PTSD symptoms. First, PTSD symptoms were found to follow 3 trajectories. second, results further revealed that the interaction could predict the trajectories of PTSD symptoms.

In all, the findings of this dissertation suggest that the CNR1 genotype x trauma exposure interaction could predict PTSD anhedonia symptom. Abnormalities of morphology in the right orbitofrontal cortex (OFC) and the right superior frontal gyrus (SFG) maybe the neural mechanisms of this relationship. In addition, the CNR1 genotype x trauma exposm0e interaction was also associated with trajectories of PTSD symptoms. Findings from the series of studies are pertinent for further understanding of the underlying mechnism of PTSD, and may help to identify novel biomakers and potential therapeutic targets for PTSD.