Dataset Information

Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders.

ABSTRACT: Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the FKBP5 gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood FKBP5 mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation status (assessed via target bisulfite sequencing) of 105 CpGs at the FKBP5 locus using data from the general population-based Study of Health in Pomerania (SHIP) (N = 203). Both direct and interaction effects with the rs1360780 single-nucleotide polymorphism were investigated. Nominally significant associations of main effects on methylation of a single CpG site were observed at intron 3, intron 7, and the 3'-end of the gene. Additionally, methylation at two clusters at the 3'-end and intron 7 were nominally associated with childhood maltreatment × rs1360780 and depressive symptoms × rs1360780, respectively. The results add to the understanding of molecular mechanisms underlying the emergence of depression and could aid the development of personalised depression therapy and drug development.

SUBMITTER: Großmann NL

PROVIDER: S-EPMC10855893 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders.

Großmann Nora L NL Weihs Antoine A Kühn Luise L Sauer Susann S Röh Simone S Wiechmann Tobias T Rex-Haffner Monika M Völzke Henry H Völker Uwe U Binder Elisabeth B EB Teumer Alexander A Homuth Georg G Klinger-König Johanna J Grabe Hans J HJ

International journal of molecular sciences 20240125 3

Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the <i>FKBP5</i> gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood <i>FKBP5</i> mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation sta ...[more]

PMID: 38338761

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Project description: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.

Dataset Information

Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders.

Publications

Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders.

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