创伤后应激障碍恐惧消退异常的脑机制研究

Recently, impaired fear extinction and related neurobiological mechanisms in posttraumatic stress disorder have become a research focus and it provides theoretical foundation to the use of exposure therapy. By applying behavioral procedure, whole night polysomnography, and magnetic resonance imaging to assess patients with posttraumatic stress disorder, trauma-exposed controls without posttraumatic stress disorder, and non-traumatised healthy controls，this study would investigate the brain mechanisms of impaired fear extinction in posttraumatic stress disorder and explore the role of sleep in consolidation of fear extinction. In specific, the aims of this proposal were: (1) to evaluate the extinction of conditioned physiologic responses to aversive stimuli and related influencing factor in posttraumatic stress disorder (e.g., genetics, cognition and neuropsychological factors, and sleep); (2) to examine the relationships among the brain anatomical alterations, functioning characteristics and abnormal fear extinction in posttraumatic stress disorder; (3) to explore the effects of sleep on memory for conditioned fear and fear extinction in posttraumatic stress disorder. This research has great importance for furthering understanding of neural mechanisms of impaired fear extinction in posttraumatic stress disorder, clarifying the role of sleep in fear extinction, and developing more effective prevention and intervention methods.

恐惧消退是当前创伤后应激障碍研究领域的重要前言课题，创伤后应激障碍恐惧消退异常的神经生物学机制是临床暴露疗法的理论基础。本项目以创伤后应激障碍患者、经历创伤暴露未患病人群及未经历过创伤暴露的健康人群为被试，综合采用行为实验法、多导睡眠监测技术和磁共振成像技术，考察创伤后应激障碍恐惧消退异常的脑机制及睡眠在其中的作用。主要的研究问题包括：（1）创伤后应激障碍恐惧消退异常状况及影响因素；（2）创伤后应激障碍恐惧消退异常的大脑结构基础和脑功能特征；（3）睡眠对创伤后应激障碍恐惧消退作用的脑机制。本项目研究不仅可以极大地丰富恐惧消退在风险性因子和创伤后应激障碍中介作用机制研究，改进创伤后应激障碍恐惧消退异常脑机制模型，探索睡眠对正常人群和创伤后应激障碍恐惧消退作用机制，而且可以为临床工作者采取恰当的治疗方法促进患者康复提供某些科学依据。

创伤后应激障碍（post-traumatic stress disorder，PTSD）是由创伤性事件导致的严重精神障碍，表现为再现、回避、负性的情绪和认知、髙警觉性等症状。心理治疗是PTSD主要的治疗手段，恐惧消退机制是暴露疗法等心理治疗的理论基础。恐惧消退异常状况及其机制是PTSD研究领域核心问题之一。本项目对经历地震灾害学生、社区群众和监狱在押服刑犯人等不同人群进行大规模的调查，识别出了PTSD的主要危险性因素，筛查出可能的PTSD研究被试，进而从行为学、分子遗传学和影像学等层面考查恐惧消退个体差异的影响因素、PTSD恐惧消退异常状况及神经生物学机制。我们的初步结果发现睡眠在PTSD发生、发展和维持中具有重要作用，BDNF基因型、睡眠和童年经历可解释恐惧消退的个体差异，海马、杏仁核和内侧前额叶神经环路结构和功能状况是恐惧消退异常的脑机制。本研究的系列发现有助于了解PTSD病因、病理机制，完善预防和治疗PTSD的方案。