倒班所致睡眠问题的变化转归及其机制

The incidence and prognosis of sleep disorders have been a hot topic in the field of health psychology and sleep medicine. Although most people can return to normal sleep after experiencing acute sleep problems, some individuals will develop persistent or chronic sleep disorders and even psychosomatic diseases. Many studies have demonstrated that sleep problems are caused by multiple genetic and environmental factors, but little is known about the transition mechanism from acute to persistent or chronic sleep disorders. There is growing evidence that gastrointestinal microbiota can regulate individual’s emotion, behavior, physical and mental status through the brain-gut axis and that life stress can alter microbiota in the gut. Our preliminary study has shown that gastrointestinal microbiota plays an important role in the transition from acute to chronic insomnia. Based on our previous work, the current project is proposed to investigate the consequences and mechanisms of sleep problems associated with shift work. In the proposed study, psychosocial and biological mechanisms and the interaction between genetic and environmental factors will be examined. In addition to environmental factors and life stress, the proposed study will specifically investigate the relationship between intestinal microenvironment (intestinal flora and related inflammatory factors, etc.) and incidence and consequences of sleep problems associated with shift work. This study will provide new evidence and/or pathways between psychosocial stress, sleep and health and may have important implications for intervention and prevention of sleep problems and for health promotion in shift workers.

睡眠障碍的发生与预后，一直是健康心理学和睡眠医学研究的热点。经历急性睡眠问题后，多数人能够较快恢复正常睡眠，有的人却迁延转化为慢性睡眠障碍，甚至引起心身疾病。众多证据肯定睡眠障碍发展进程与遗传有关，但其传递机制不明确；已有证据显示肠道菌群可通过脑-肠轴调控宿主的行为和身心状态，而个体应激对其共生的微生物有明确影响，我们的前期研究也显示肠道菌群在急性失眠向慢性失眠转化过程中有显著的作用。本项目拟在前期工作基础上，对已经入组的倒班所致睡眠问题的不同变化转归类型进行长时程追踪，进一步探讨其长时程的转化迁延规律及影响其变化转归的心理社会机制、遗传与环境交互作用机制。在关注外部环境与生活事件影响的同时，重点考察体内的肠道微环境（肠道菌群及其相关炎症因子等）与睡眠问题变化转归的关系。本研究将为理解心理应激机制和职业心理保健提供新思路，也为更深入的睡眠医学研究提供新视角。

人们在倒班工作或者昼夜节律紊乱以后，大多会出现一些急性的睡眠问题，但多数人会逐渐适应或者在停止倒班以后睡眠问题就会恢复，少部分人的暂时性的急性睡眠问题会转变为睡眠障碍。本项目在影响失眠发展的心理社会因素以及肠道微环境、炎症细胞因子及认知功能方面取得了进展。.对于失眠障碍的病理机制部分，采用16S rDNA测序方法分析被试肠道微生物群落结构特点，并分析与失眠障碍发展进程有关的关键微生物。采用酶联免疫方法检测被试血浆炎症因子IL-1β，IL-6，TNF-α水平。对于失眠患者的认知功能，采用注意网络测验（attention network test, ANT）检测被试注意网络功能；采用情绪记忆范式检测被试记忆功能。利用生物信息学分析的方法探索与失眠障碍发展进程有关的关键微生物与炎症因子、认知功能之间的相互作用关系。.通过多元追踪测评和回归分析发现，情绪调节困难，抑郁情绪是急性失眠障碍与慢性失眠障碍共同的危险性因素，神经质人格特性是慢性失眠的重要危险性因素。失眠患者确实存在肠道微生态失调，Lachnospira & Bacteroides，Faecalibacterium & Blautia可能分别是与急性/慢性失眠有关的关键功能菌。失眠患者的肠道菌群失调，可能通过引起体内的炎症反应，进而导致失眠患者认知功能受损。失眠障碍对个体认知功能有显著影响，表现在执行控制网络功能下降。失眠障碍患者对正性和中性情绪刺激倾向于负向评价，并且随着失眠病程延长该倾向加重，而对负性情绪刺激的记忆编码却完整保留。失眠诊断功能菌可能通过影响失眠患者体内IL-1β水平，从而对失眠患者执行控制网络效率产生影响。.新冠疫情后，我们敏锐地意识到，居家隔离人群往往生活节律紊乱，睡眠问题严重，容易引发系列心理健康问题。在本项目原有研究计划基础上，于疫情爆发期、控制转折期、常态化防控期对居家隔离大学生人群展开了生活节律和睡眠问题及其所致系列心理健康问题变化转归的追踪研究。这部分研究已得到国内外同行高度关注，有三篇报告已经成为了ESI高被引论文。特别是撰写了系列资政报告，被教育部等国家部委综合采用。