Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression

JOURNAL OF AFFECTIVE DISORDERS

卷:206

Article

Bustamante, Angela C.¹  Aiello, Allison E.²  Galea, Sandro³  Ratanatharathorn, Andrew⁴  Noronha, Carol⁵  Wildman, Derek E.^6,7  Uddin, Monica^1,7,8 

[1] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA

[2] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA

[3] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA

[4] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA

[5] Wayne State Univ, Detroit, MI 48201 USA

[6] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA

[7] Univ Illinois, Carl R Woese Inst Genom Biol, Champaign, IL 61801 USA

[8] Univ Illinois, Dept Psychol, 603 E Daniel St, Champaign, IL 61820 USA

关键词: Development;    Epigenetics;    Gene expression;    Childhood maltreatment;    Depression;   

DOI  :  10.1016/j.jad.2016.07.038

来源: Elsevier

【 摘 要 】

Introduction: Altered DNA methylation (DNAm) levels of hypothalamic-pituitary-adrenal (HPA) axis genes has been associated with exposure to childhood maltreatment (CM) and depression; however, it is unknown whether CM and depression have joint and potentially interacting effects on the glucocorticoid receptor (NR3C1) DNAm. We investigated the impact of CM and lifetime major depressive disorder (MDD) on NR3C1 DNAm and gene expression (GE) in 147 adult participants from the Detroit Neighborhood Health Study. Methods: NR3C1 promoter region DNAm was assessed via pyrosequencing using whole blood-derived DNA. Quantitative RT-PCR assays measured GE from leukocyte-derived RNA. Linear regression models were used to examine the relationship among CM, MDD, and DNAm. Results: Both CM and MDD were significant predictors of NR3C1 DNAm: CM was associated with an increase in DNAm in an EGR1 transcription factor binding site (TFBS), whereas MDD was associated with a decrease in DNAm downstream of the TFBS. No significant CM-MDD interactions were observed. CM alone was associated with significantly lower NR3C1 GE. Limitations: Our report of CM is a retrospective self-report of abuse, which may introduce recall bias. DNAm was measured in whole blood and may not reflect brain-derived DNAm levels. Conclusions: CM and MDD are both associated with altered DNAm levels in the NR3C1 promoter region, however the location and direction of effects differ between the two exposures, and the functional effects, as measured by GE, appear to be limited to CM exposure alone. CM exposure may be biologically embedded in this key HPA axis gene.

【 授权许可】

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