@article {443, title = {Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses.}, journal = {Epigenetics}, volume = {3}, year = {2008}, month = {2008 Mar-Apr}, pages = {97-106}, abstract = {

BACKGROUND: In animal models, variations in early maternal care are associated with 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.

OBJECTIVE: To study this in humans, relationships between prenatal exposure to 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 age three months were examined.

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.

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

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

}, keywords = {Adult, Antidepressive Agents, Second-Generation, Base Sequence, CpG Islands, Depression, DNA Methylation, Exons, Female, Fetal Blood, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Infant, Leukocytes, Mononuclear, Molecular Sequence Data, Mothers, Pituitary-Adrenal System, Pregnancy, Pregnancy Complications, Promoter Regions, Genetic, Receptors, Glucocorticoid, Serotonin Uptake Inhibitors}, issn = {1559-2308}, author = {Oberlander, Tim F and Weinberg, Joanne and Papsdorf, Michael and Grunau, Ruth and Misri, Shaila and Devlin, Angela M} }