Article Text

PRENATAL EXPOSURE TO MATERNAL DEPRESSION, NEONATAL METHYLATION OF HUMAN GLUCOCORTICOID RECEPTOR GENE (NR3C1) AND INFANT CORTISOL STRESS RESPONSES
  1. T F Oberlander1,
  2. J Weinberg2,
  3. M Papsdorf1,
  4. R E Grunau1,
  5. S Misri3,
  6. A M Devlin4
  1. 1Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
  2. 2Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
  3. 3Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
  4. 4Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada

Abstract

Objective Early variations in maternal care in animals leads to differences in hypothalamic-pituitary-adrenal (HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression. To examine this in humans, relationships between prenatal maternal mood and the methylation status of a CpG-rich region in the promoter and exon 1F of the human GR gene (NR3C1) in newborns and HPA stress reactivity at 3 months.

Methods Methylation status of a CpG-rich region of the NR3C1 gene, including exon 1F, in cord blood mononuclear cell DNA was quantified by bisulfite pyrosequencing in infants of depressed mothers treated with a serotonin reuptake inhibitor antidepressant (SRI) (n = 33), in infants of depressed non-treated mothers (n = 13), and in infants of non-depressed/non-treated mothers (n = 36). To study the functional implications of the newborn methylation NR3C1status, HPA function was assessed at 3 months using salivary cortisol obtained before and following a non-noxious stressor and at a late afternoon basal time.

Results Prenatal exposure to increased third trimester maternal depressed/anxious mood was associated with increased methylation of NR3C1 at a predicted NGFI-A binding site. Increased NR3C1 methylation at this site was also associated with increased salivary cortisol stress responses at 3 months, controlling for prenatal SRI exposure, postnatal age, and pre- and postnatal maternal mood.

Conclusions Methylation status of the human NR3C1 gene in newborns is sensitive to prenatal maternal mood, offering a potential epigenetic process that links antenatal maternal mood and altered HPA stress reactivity during infancy.

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