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

Abstract Background Depressive 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. Howev...

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Main Authors: Wenyan Li, Wanxin Wang, Wenjian Lai, Xiuwen Li, Liwan Zhu, Jingman Shi, Kayla M. Teopiz, Roger S. McIntyre, Lan Guo, Ciyong Lu
Format: Article
Language:English
Published: BMC 2022-11-01
Series:BMC Psychiatry
Subjects:
Online Access:https://doi.org/10.1186/s12888-022-04392-2
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author Wenyan Li
Wanxin Wang
Wenjian Lai
Xiuwen Li
Liwan Zhu
Jingman Shi
Kayla M. Teopiz
Roger S. McIntyre
Lan Guo
Ciyong Lu
author_facet Wenyan Li
Wanxin Wang
Wenjian Lai
Xiuwen Li
Liwan Zhu
Jingman Shi
Kayla M. Teopiz
Roger S. McIntyre
Lan Guo
Ciyong Lu
author_sort Wenyan Li
collection DOAJ
description Abstract Background Depressive 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. Methods This 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. Results The 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. Conclusion The 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.
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spelling doaj.art-be0c0e5ba31040fc81f79e705c17fd082022-12-22T02:48:33ZengBMCBMC Psychiatry1471-244X2022-11-0122111210.1186/s12888-022-04392-2The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control studyWenyan Li0Wanxin Wang1Wenjian Lai2Xiuwen Li3Liwan Zhu4Jingman Shi5Kayla M. Teopiz6Roger S. McIntyre7Lan Guo8Ciyong Lu9Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityMood Disorders Psychopharmacology Unit, University Health NetworkMood Disorders Psychopharmacology Unit, University Health NetworkDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen UniversityAbstract Background Depressive 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. Methods This 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. Results The 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. Conclusion The 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.https://doi.org/10.1186/s12888-022-04392-2Depressive symptomsFKBP5 DNA methylationSex differencesSocial-environmental factorsNested case-control study
spellingShingle Wenyan Li
Wanxin Wang
Wenjian Lai
Xiuwen Li
Liwan Zhu
Jingman Shi
Kayla M. Teopiz
Roger S. McIntyre
Lan Guo
Ciyong Lu
The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
BMC Psychiatry
Depressive symptoms
FKBP5 DNA methylation
Sex differences
Social-environmental factors
Nested case-control study
title The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
title_full The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
title_fullStr The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
title_full_unstemmed The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
title_short The association of FKBP5 gene methylation, adolescents’ sex, and depressive symptoms among Chinese adolescents: a nested case-control study
title_sort association of fkbp5 gene methylation adolescents sex and depressive symptoms among chinese adolescents a nested case control study
topic Depressive symptoms
FKBP5 DNA methylation
Sex differences
Social-environmental factors
Nested case-control study
url https://doi.org/10.1186/s12888-022-04392-2
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