PER1基因DNA甲基化在大学生睡眠时型与抑郁症状的关联中具有负向调节作用

Prospective study of the association between chronotypes and depressive symptoms in Chinese university students:

moderating effects of PER1 gene DNA methylation

中国大学生睡眠时型与抑郁症状关联的前瞻性研究:PER1基因DNA甲基化的调节作用

Author: Tingting Li, Yuxuan Cao, Panfeng Zhou, Yang Xie, Shuman Tao, Liwei Zou, Yajuan Yang, Fangbiao Tao, Xiaoyan Wu

Source: Chronobiology international

DOI: 10.1080/07420528.2024.2337891.

Abstract

Most studies have shown a link between chronotypes and mental health and have identified evening chronotypes (E-types) as a potential risk for depressive symptoms. However, the mechanisms behind this association remain unknown. Abnormal expression of the PER1 gene was not only associated with circadian rhythm disturbance, but also closely related to mental illness. Therefore, this study aimed to examine the association of chronotype with depressive symptoms, and further explore the moderating effects of the PER1 gene DNA methylation on chronotypes and depressive symptoms in Chinese university students. In a stratified cluster sampling design, chronotype and depressive symptoms were assessed in 1 042 university students from 2 universities in a two-year prospective survey from April 2019 to October 2020. The survey was conducted once every 6 months, corresponding to the time points in April 2019 (T0), October 2019 (T1), April 2020 (T2), and October 2020 (T3). At T0, the Morning and Evening Questionnaire 5 (MEQ-5) was adopted to assess chronotype. At T0-T3, the Patient Health Questionnaire 9 (PHQ-9) was adopted to investigate depressive symptoms. Meanwhile, at T0, participants were subjected to a health check-up trip in the hospital, and blood samples were taken from the students to measure the PER1 gene DNA methylation levels. Binary logistic regression was used to analyze the association of chronotypes with depressive symptoms. The depression/total depression group was coded as 1, while the remaining participants was defined as one group, and was coded as 0. The PROCESS plug-in of SPSS software was used to analyze the moderating effects of PER1 gene DNA methylation on the association of chronotype with depressive symptoms. After adjusting for covariates, the results indicated that T0 E-types were positively correlated with T0-T3 depression/total depression in female university students. Furthermore, the PER1 gene DNA methylation has negative moderating effects between T0 chronotype and T3 depressive symptoms and has a sex difference. This study can provide more favorable scientific value for the prevention and control of depression in university students.

Keywords: Chronotypes; Depressive symptoms; DNA methylation; Moderating effects

摘要

大多数研究表明，睡眠时型与心理健康之间存在联系，并将夜晚型睡眠时型确定为抑郁症状的潜在风险。然而，这种关联背后的机制尚不清楚。PER1基因的异常表达不仅与昼夜节律紊乱有关，还与精神疾病密切相关。因此，本研究旨在探讨中国大学生睡眠时型与抑郁症状的关联，进一步探讨PER1基因DNA甲基化在睡眠时型与抑郁症状关联中的调节作用。本研究采用分层整群抽样设计，于2019年4月至2020年10月对来自中国两所大学的1042名大学生进行了为期两年的前瞻性调查，以评估他们的睡眠时型和抑郁症状。调查每6个月进行一次，时间点分别为2019年4月(T0)、2019年10月(T1)、2020年4月(T2)和2020年10月(T3)。在T0时，使用清晨型与夜晚型量表—5项（Morning and Evening Questionnaire 5，MEQ-5）评价大学生睡眠时型。在T0-T3时，采用患者健康问卷—9项（Patient Health Questionnaire 9，PHQ-9）评价大学生抑郁症状。同时，在T0时，参与者在医院接受了一次健康检查，提供了血液样本以测量PER1基因DNA甲基化水平。本研究采用二元logistic回归模型分析睡眠时型与抑郁症状的关联。其中，抑郁/总抑郁组被编码为1，而其余参与者被定义为一组，编码为0。还采用SPSS软件中的PROCESS插件分析PER1基因DNA甲基化在睡眠时型与抑郁症状关联中的调节作用。调整混杂因素后，结果显示T0夜晚型睡眠时型与T0-T3抑郁/总抑郁只在女大学生中呈正向关联。此外，本研究还发现PER1基因DNA甲基化在T0睡眠时型与T3抑郁症状之间具有负向调节作用，且存在性别差异。本研究可为大学生抑郁的防治提供更有利的科学价值。