FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study

Angela C. Bustamante, Allison E. Aiello, Guia Guffanti, Sandro Galea, Derek E. Wildman, Monica Uddin

Research output: Research - peer-reviewArticle

Abstract

Exposure to childhood maltreatment increases the risk of developing mental illness later in life. Childhood maltreatment and depression have both been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis—a key regulator of the body's stress response. Additionally, HPA axis dysregulation has been implicated in the etiology of a range of mental illnesses. A substantial body of work has shown history of childhood maltreatment alters DNA methylation levels within key HPA axis genes. We therefore investigated whether one of these key genes, FKBP5 mediates the relationship between childhood maltreatment and depression, and assessed FKBP5 DNA methylation and gene expression within 112 adults from the Detroit Neighborhood Health Study (DNHS). DNA methylation was assessed in 4 regions, including the upstream promoter, downstream promoter, and two glucocorticoid response elements (GREs) via pyrosequencing using whole blood derived DNA; Taqman assays measured relative RNA expression from leukocytes. Mediation analyses were conducted using sequential linear regression. Childhood maltreatment was significantly associated with depression symptom severity (FDR < 0.006), but was not a significant predictor of DNA methylation in any of the four loci examined. FKBP5 showed elevated expression levels in participants with vs. without a history of depression (p < 0.001); no significant difference in gene expression levels was observed in relation to childhood maltreatment (p > 0.05). Our results suggest DNA methylation does not mediate the childhood maltreatment-depression association in the DNHS.

LanguageEnglish (US)
Pages39-48
Number of pages10
JournalJournal of Psychiatric Research
Volume96
DOIs
StatePublished - Jan 1 2018

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DNA Methylation
Health
Gene Expression
Genes
Response Elements
Glucocorticoids
Linear Models
Leukocytes
RNA
DNA

Keywords

  • Childhood maltreatment
  • Epigenetics
  • Gene expression
  • Major depressive disorder
  • Mediation

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study. / Bustamante, Angela C.; Aiello, Allison E.; Guffanti, Guia; Galea, Sandro; Wildman, Derek E.; Uddin, Monica.

In: Journal of Psychiatric Research, Vol. 96, 01.01.2018, p. 39-48.

Research output: Research - peer-reviewArticle

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