Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults

Dev Psychopathol. 2016 Nov;28(4pt2):1319-1331. doi: 10.1017/S0954579416000870. Epub 2016 Oct 3.


Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus-pituitary-adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects. We present recent evidence related to epigenetic regulation of genes involved in hypothalamus-pituitary-adrenal axis regulation, namely, the glucocorticoid receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506 binding protein 51 gene (FKBP5), after childhood adversity and associations with risk for psychiatric disorders. Implications for the development of interventions and future research are discussed.

Publication types

  • Review

MeSH terms

  • Adult
  • Child
  • Child Abuse / psychology*
  • Epigenesis, Genetic / genetics*
  • Female
  • Glucocorticoids / physiology*
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Mental Disorders / genetics
  • Mental Disorders / psychology
  • Pituitary-Adrenal System / physiopathology*
  • Receptors, Glucocorticoid / genetics*
  • Risk Factors
  • Signal Transduction / genetics*
  • Social Environment
  • Stress, Psychological / complications*
  • Stress, Psychological / psychology
  • Tacrolimus Binding Proteins / genetics


  • Glucocorticoids
  • NR3C1 protein, human
  • Receptors, Glucocorticoid
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5