| ObjectivesTo describe the prevalence of chronotype and depressive symptoms and examine the associations between chronotype and depressive symptoms in college students.The biological indicator dim light melatonin onset（DLMO）was adopted to verify the association of chronotype and depressive symptoms.Furthermore,the moderating effect of clock gene DNA methylation on the longitudinal association between chronotype and depressive symptoms in college students were explored.MethodsFrom April to May 2019,the cluster random sampling method was adopted to select one medical university in Hefei City,Anhui Province and one comprehensive normal university in Shangrao City,Jiangxi Province.All freshmen from two majors at each university were selected to complete a questionnaire survey.A total of 1 179questionnaires were sent out,1 151 were returned and 1 135 were valid.The effective questionnaire rate was 98.6%.College students completed the electronic anonymous questionnaire by using mobile phones to scan the quick response code.The survey included basic information and characteristics,chronotype,depressive symptoms,sleep quality and physical activity level.At baseline,chronotype,sleep quality and physical activity level were assessed by the MEQ-5,PSQI and IPAQ-SF,respectively;depressive symptoms was assessed by the PHQ-9.At the same time,saliva samples were collected from the subjects at 5 time points（21:00,22:00,23:00,24:00,1:00）under dim light conditions.A total of 709 saliva samples were collected.The level of melatonin in human saliva was determined by ELISA,thus calculating the DLMO.According to the principle of informed consent,students were organized to go to the nearest third-class hospital for medical examination,including height,weight,waist circumference,routine blood tests,blood pressure and liver function.A total of 744 blood samples were collected.Methy Target TMwas used to detect the clock gene DNA methylation（ARNTL,CLOCK,CRY1,CRY2,CSNK1D,CSNK1E,NPAS2,NR1D1,PER1,PER2,PER3）.Based on the baseline survey,1 135 college students were followed up from May to June 2020,with a follow-up of 1 100（35 were lost to follow-up,with a loss to follow-up rate of 3.1%）.Statistical analysis was performed using SPSS version 23.0.Categonomic variables were represented as rates（%）.The chi-square test was performed to assess differences between groups.Nonnormally distributed data was compared using nonparametric tests.A binary logistic regression model was established to analyse the association of chronotype and depressive symptoms after controlling for learning burden,residential background,parental education level,physical health status,family economic conditions,sleep quality and physical activity level.Generalized linear model was established to analyse the association of DLMO and depressive symptoms and to perform moderating effects analysis by using the PROCESS plug-in in SPSS software.The inspection level wasα=0.05.ResultsAt baseline,the prevalence of the morning type,intermediate type,and evening type chronotypes were 18.4%,71.1%,and 10.5%,respectively.The prevalence of depressive symptoms was 42.6%.A binary logistic regression model was used to analyse the association between chronotype and depressive symptoms,and morning type was set as the reference.The model 1（OR=2.45,95%CI:1.55～3.89）and model 2（OR=1.97,95%CI:1.20～3.24）showed a positive association between evening type and depressive symptoms（P<0.001）.According to gender stratified analysis,this association（crude OR=3.76,95%CI:2.06～6.87;adjusting OR=3.06,95%CI:1.60～5.84）only remained for female college students（P<0.001）.The generalized linear model was used to analyse the association between chronotype and DLMO.The results showed that there was a negative association between chronotype and DLMO（β=-0.040,P<0.05）.According to gender stratified analysis,this association only remained for female college students（β=-0.070,P<0.05）.The generalized linear model was used to analyse the association between DLMO and depressive symptoms.The results were not statistically significant,either in overall sample or stratified by gender.At follow-up,the prevalence of depressive symptoms was 24.3%.A binary logistic regression model was used to analyse the longitudinal association between baseline chronotype and depressive symptoms,and morning type was set as the reference.The model 1 and model 2 showed a positive association between evening type and 1 years later depressive symptoms,but there was no statistically significant difference.According to gender stratified analysis,this association（crude OR=2.44,95%CI:1.29～4.59;adjusting OR=2.04,95%CI:1.05～3.97）only remained for female college students（P<0.001）.The generalized linear model was used to analyse the longitudinal association between DLMO and depressive symptoms.The results were not statistically significant,either in overall sample or stratified by gender.Moderated mediation analysis revealed that the DNA methylation of ARNTL and PER1 genes significantly moderated the longitudinal association of chronotype and depressive symptoms（β=-48.975,P<0.05;β=-49.046,P<0.05）.After stratified by sex,the DNA methylation of ARNTL,CSNK1D,NPAS2,PER1 and CSNK1E genes significantly moderated the longitudinal association of chronotype and depressive symptoms in female college students（β=-60.415,P<0.05;β=-11.911,P<0.05;β=-5.468,P<0.05;β=-54.934,P<0.05;β=54.811,P<0.05）.However,in male college students,the DNA methylation levels of the 11 clock genes showed no moderating effect in the longitudinal association of chronotype and depressive symptoms.ConclusionsCollege students’evening-type chronotype and depressive symptoms showed a positive and sex-specific association.Among female college students,the baseline evening-type chronotype had positive predictive effects on 1 years later depressive symptoms.Furthermore,clock gene DNA methylation played a moderating effect on the longitudinal association of baseline chronotype with depressive symptoms,gender-stratified analyses indicated that female drove these associations. |
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