手机依赖及体力活动不足的独立和联合作用效应对大学生抑郁的影响：生物钟相关基因作用机制研究

Problematic mobile phone use (PMPU) and physical inactivity are both risk factors of depression among college students, the synergistic effect is possible existed when the two factors combined. However, previous studies were mainly cross-sectional study, which were difficult to reveal the directionality of PMPU and physical inactivity and depression; therefore, prospective cohort study should be launched for verification and be revealed with its potential mechanism. Preliminary researches showed that sleep insufficiency and disorders were the mediating factors in the correlation between PMPU and physical inactivity and depression, and clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. Thereby we hypothesize that circadian clock related genes are possible biological basis is deduced. This research combines cross-sectional study with prospective cohort study to mutually test the impacts that circadian clock genes expression and their DNA methylation exert on the independent and combined effect of PMPU and physical inactivity on depression among college students; and to expound the causality based on the nested case-control design. The current research can respectively answer the following questions: the independent and combined effects of PMPU and physical inactivity and depression among college students; and then expound the possible biological mechanism of the effects from the perspective of circadian clock genes and their DNA methylation. This research hopes to reveal the biological mechanism of the combined effects of PMPU and physical inactivity on depression among college student on new perspectives, and to provide evidence for the mental health intervention among college students.

手机依赖和体力活动不足均是大学生抑郁的危险因素，二者共存的健康影响可能存在协同效应。既往多为横断面研究，难以揭示手机依赖和体力活动不足与抑郁的方向性，需要队列研究加以验证，且潜在机制有待揭示。前期研究发现睡眠不足或睡眠障碍是手机依赖、体力活动不足与大学生抑郁关联的中介因素，而生物钟基因在生物节律的形成及调节睡眠稳态中起重要作用，推论生物钟相关基因表达是其生物学基础之一。研究采用横断面与前瞻性队列研究验证生物钟相关基因表达及其DNA甲基化在联结手机依赖、体力活动不足与大学生抑郁关联中的作用，并基于巣式病例对照研究来阐明因果关系。研究可分别回答手机依赖、体力活动不足单独和共存对大学生抑郁的独立及联合作用效应强度，并从生物钟相关基因表达及DNA甲基化水平的改变来解释该作用的可能生物学机制。研究可望从新的视角揭示手机依赖、体力活动不足共存对大学生抑郁影响的生物学机制，为大学生心理健康干预提供依据。

研究依托项目负责人建立的大学生行为与健康队列，目前该队列已经完成基线调查和4次随访，研究对象配合度高，生物样本采集及实验室检测标准严格，是一个成熟系统的研究队列。. 本研究主要发现大学生中等强度和大强度体力活动水平与抑郁症状呈负向关联，手机依赖行为与大学生抑郁症状呈正向关联，且大学生体力活动不足和手机依赖对抑郁症状存在相乘交互作用。此外，本研究还发现在不同基线体力活动水平分组中CRY1、CRY2、CSNK1D、CSNK1E、PER1、PER3生物钟基因DNA甲基化水平存在差异，不同抑郁分组CRY1基因DNA甲基化水平存在差异。部分生物钟基因（PER3、NPAS2、CLOCK、CRY1、CRY2、CSNK1E）DNA甲基化水平在体力活动、手机依赖与抑郁症状的关联中具有调节效应。. 综上，本研究确立了手机依赖及体力活动不足独立与共存行为与大学生抑郁的关联，揭示了生物钟相关基因DNA甲基化在联接上述关联中的作用机制，可为大学生抑郁的早期干预提供循证依据。. 本课题共发表标注基金的论文29篇，其中SCI论文11篇，累计影响因子为51.81；中文核心期刊论文18篇。共培养2名博士研究生和1名硕士研究生毕业，在读硕士研究生4名。课题组成员中3人获评副高职称，2人获评中级职称，研究现场主要合作者晋升副高职称1人。