The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study

BMC Psychiatry

Research

Wenyan Li¹  Liwan Zhu¹  Wenjian Lai¹  Jingman Shi¹  Wanxin Wang¹  Xiuwen Li¹  Lan Guo¹  Ciyong Lu¹  Kayla M. Teopiz²  Roger S. McIntyre³ 

[1] Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Rd 2, 510080, Guangzhou, China;Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada;Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada;Department of Pharmacology, University of Toronto, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;

关键词: Depressive symptoms;    FKBP5;    Sex differences;    Social-environmental factors;    Nested case-control study;   

DOI  :  10.1186/s12888-022-04392-2

 received in 2022-04-13, accepted in 2022-11-15,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDepressive symptoms among adolescents are a serious health concern around the world. Altered DNA methylation in the FK506 binding protein 5 (FKBP5) gene has been reported to regulate stress response, which has been reported to be closely associated with depressive symptoms. However, most of the contributing studies have been conducted among adults and relatively few studies have considered the effect of disparate social influences and sex differences on the DNA methylation of FKBP5 in persons with depressive symptoms. The present study aimed to test the associations of FKBP5 DNA methylation and depressive symptoms among adolescents and explore possible sex differences in the foregoing associations.MethodsThis study was conducted using a nested case-control design within a longitudinal cohort study from January 2019 to December 2019. Adolescents aged 12 to 17 years from 69 classes in 10 public high schools located in Guangdong province of China participated in this research. Students with persistent depressive symptoms that reported having depressive symptoms at both baseline and follow-up were treated as the case group, and those without depressive symptoms were randomly selected as the control group. Our study finally included 87 cases and 151 controls. Quantitative methylation analyses of the selected gene were carried out by MassARRAY platform System.ResultsThe overall DNA methylation trend of FKBP5 CpG sites in the case group was lower in comparison to the control group. Compared to healthy controls, lower methylation percentage of FKBP5-12 CpG 1 was observed in adolescents with persistent depressive symptoms after adjusting for covariates (case: 0.94 ± 2.00, control: 0.47 ± 0.92; F = 5.41, P = 0.021), although the statistical significance of the difference was lost after false discovery rate correction (q > 0.05). In addition, the hypomethylation of FKBP5-12 CpG 1 was approaching significance after adjustment for social-environmental factors (aOR = 0.77; P = 0.055), which indicated that no independent association was detected between hypomethylation of FKBP5 CpG sites and persistent depressive symptoms. Furthermore, in the present study, we were unable to identify sex differences in the association of FKBP5 gene methylation with depressive symptoms.ConclusionThe decreased methylation level of FKBP5 was observed in adolescents with persistent depressive symptoms, albeit non-significant after correction for multiple testing. Our results presented here are preliminary and underscore the complex gene-environment interactions relevant to the risk for depressive symptoms.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

12888_2022_4392_Article_IEq3.gif

12888_2022_4392_Article_IEq2.gif

12888_2022_4392_Article_IEq1.gif

Fig. 2

Fig. 1