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）是个体暴露在异乎寻常的威胁性或灾难性应激事件后出现的一种持续而严重的心理疾患。遗传因素在PTSD 的发病过程中起到重要作用。人类和动物的研究显示催产素及其受体通路可能是个体经历严重创伤性事件后，出现异常心理与生物应激反应的重要介体，提示其在 PTSD 的发生和发展中可能具有重要的作用，但是目前尚无研究系统而深入地探讨二者的关系。本研究以遗传与环境交互作用的视角，聚焦于催产素受体基因（OXTR，rs1042778 位点变异）与创伤暴露的交互作用和PTSD 的关系，系统的探讨催产素受体系统在PTSD 发生、发展、转化和共病中的作用。
本论文共包含四个部分的研究。第一部分包含三个研究，旨在考察催产素受体基因与创伤暴露的交互作用和PTSD 症状的关系。研究1 分析催产素受体基因与创伤暴露的交互作用和PTSD 总体症状的关系，结果表明在女性样本中，催产素受体基因与创伤暴露的交互作用可以（边缘）显著预测PTSD 总体症状，在男性样本中预测关系不显著。研究2 探讨在该样本中，PTSD 的维度结构及跨性别的稳定性。结果发现，在不同性别中，7 维混合模型均能最好的拟合数据，同时该模型在不同性别中测量恒等。研究3 在研究2 的基础上，进一步分析了催产素受体基因与创伤暴露的交互作用，和PTSD 的7 个异质性症状簇的关系。分析结果发现，在女性中，交互作用可以显著预测闯入和外化行为症状簇，对其他症状簇无显著预测。在男性样本中预测关系不显著。
第二部分包含两个研究，旨在考察催产素受体基因与创伤暴露的交互作用和PTSD 发展变化的关系。研究4 使用潜在类别增长模型（LCGA）分析了不同性别中四个时间点的发展轨迹。结果发现，在女性中，发展轨迹呈现三个组别（低症状缓解组、中等症状缓解组和高症状组）。在男性中，呈现两个组别（低症状缓解组和持续中等症状组）。研究5 进一步分析了催产素受体基因与创伤暴露的交互作用对组别的预测，结果发现交互作用不能显著预测组别。
第三部分包含两个研究，旨在考察催产素受体基因与创伤暴露的交互作用和PTSD 症状转化的关系。研究6 使用潜在转化分析（LTA）的方法，分析了两个时间点间个体组别的转化。结果发现，在两个时间点中，PTSD 症状的三个组别能够最好的拟合数据，个体在不同时间点组别不是完全稳定的，会出现量的变化。研究7 进一步分析了催产素受体基因与创伤暴露的交互作用对组别转化的预测，结果发现交互作用不能显著预测个体组别的转化。
第四部分包含两个研究，旨在考察交互作用和PTSD-抑郁症状合并模式的关系。研究8 使用潜在剖面分析（LPA）的方法，分析了PTSD 和抑郁症状合并的模式。结果发现，女性样本中，PTSD 和抑郁症状的合并模式呈现为三条平行的曲线，在男性样本中，PTSD 和抑郁症状的合并模式呈现为两条平行的曲线。研究9 进一步分析了催产素受体基因与创伤暴露的交互作用对症状合并模式组别的预测，结果发现交互作用不能显著预测症状合并的组别。
总的来看，本研究发现，在女性中，催产素受体基因与创伤暴露的交互作用可以预测PTSD 总体症状以及闯入/外化行为症状簇，但是在男性中不能显著预测。同时，交互作用对于PTSD 的发展变化、转化以及PTSD-抑郁共病没有显著的预测作用。本研究的系列发现有助于阐释催产素受体系统在PTSD 发生、发展中的作用，促进对PTSD 发病机制的理解，并可为临床实践提供针对该疾患的生物标记与干预靶点。

Posttraumatic stress disorder (PTSD) is a complex and severe mental disorder triggered by exposure to an extraordinarily traumatic event. Many studies have provided evidence supporting a genetic predisposition to PTSD. Human and animal studies suggest that the oxytocin-oxytocin 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 dissertation focused on the associations between the oxytocin receptor gene (OXTR， rs1042778 genotype) x trauma exposure interaction and PTSD, and aimed to systematically investigate the role of the oxytocin receptor system in the occurrence, development, transition and comorbidity of PTSD.
The studies were comprised of four sections. Section 1 contained three studies to investigate the associations between the rs1042778 genotype x trauma exposure interaction and PTSD symptoms. Study 1 aimed to examine the association between interaction and total PTSD symptoms. The results showed that the interaction was associated with total PTSD symptoms in females, but not in males. Study 2 investigated the dimensionality underlying DSM-5 PTSD symptoms, and examining the stability of PTSD symptom structure across gender. Confirmatory factor analyses revealed that the seven-factor hybrid PTSD model provided the best fit to the data for both females and males. Moreover, measurement equivalence of this model held across gender. On the basis of Study 2, Study 3 showed that the interaction was only associated with severity of the intrusion and externalizing behaviors symptoms in females.
Two studies in Section 2 intended to verify the relationships between the rs1042778 genotype x trauma exposure interaction and the trajectories of PTSD symptoms. In Study 4, PTSD symptoms were found to follow 3 trajectories in females, and 2 trajectories in males. Study 5 further revealed that the interaction could not predict the trajectories of PTSD symptoms both in females and males.
Section 3 includes two studies focused on the effect of interaction on the transition of PTSD symptom profiles. Study 6 aimed to determine the population-based profiles of posttraumatic stress disorder (PTSD) symptomatology and the longitudinal patterns of transitions across these profiles. Latent profile analyses (LPA) identified three classes at each time point. Latent transition analysis (LTA) revealed notable movement between classes over time. In Study 7, it was found that the interaction was not associated with the transition.
Finally, two studies in Section 4 were conducted with the goal to examine the relationships between the rs1042778 genotype x trauma exposure interaction and patterns of co-occurring PTSD and depression symptoms. Study 8 showed that a 3-class solution in females and a 2-class solution in males fit the data best. According to Study 9, the interaction was not associated with patterns of co-occurring PTSD and depression symptoms.
In all, the findings of this dissertation suggest that the rs1042778 genotype x trauma exposure interaction could predict total PTSD symptoms and the intrusion/externalizing behaviors symptoms in females. However, it was not associated with trajectories, transition and comorbidity 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.