Prospective study of the association between chronotypes and depressive symptoms in Chinese university students: Moderating effects of PER1 gene DNA methylation

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

Acknowledgments

We acknowledge all the participants who participated in this project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Designed the experiments: Xiaoyan Wu, Fangbiao Tao. Conducted the experiments: Yajuan Yang, Shuman Tao. Analyzed the data: Yuxuan Cao, Tingting Li. Contributed materials: Liwei Zou, Panfeng Zhou, Yang Xie. Wrote the essay: Tingting Li.

Data availability statement

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

Ethical approval and consent to participate

The Ethics Committee of Anhui Medical University approved this study (NO: 20170291). Written informed consent was obtained from all participants.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number:82173542, 82373592, 82073578]; Grants for Scientific Research Level Improvement Plan from Anhui Medical University [2022×kjT004].