title: Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood.
abstract: BACKGROUND
  The methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene.
  
  
  METHODS
  We examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells.
  
  
  RESULTS
  Univariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8% (p = 0.023) during T1. Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9% and PVE:9.0%; Fear of delivery T2: PVE:8.0%, Fear of integrity T2: PVE:6.0% and STAI T2: PVE:5.9%) - (F12.13: PC PRAQ T1: PVE:6.9%, fear of integrity T2: PVE:6.0% and fear of delivery T2: PVE:8.0%)] and cortisol (F38.39: PVE:8.9%) in T2.
  
  
  CONCLUSIONS
  These data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.
authors.affiliation: Department of Psychiatry, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. titia.hompes@uz.kuleuven.be
authors.forename: Titia
authors.initials: T
authors.lastname: Hompes
authors.forename: Benedetta
authors.initials: B
authors.lastname: Izzi
authors.forename: Edith
authors.initials: E
authors.lastname: Gellens
authors.forename: Maarten
authors.initials: M
authors.lastname: Morreels
authors.forename: Steffen
authors.initials: S
authors.lastname: Fieuws
authors.forename: Anne
authors.initials: A
authors.lastname: Pexsters
authors.forename: Ganel
authors.initials: G
authors.lastname: Schops
authors.forename: Myriam
authors.initials: M
authors.lastname: Dom
authors.forename: Rieta
authors.initials: R
authors.lastname: Van Bree
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.forename: Johan
authors.initials: J
authors.lastname: Verhaeghe
authors.forename: Bernard
authors.initials: B
authors.lastname: Spitz
authors.forename: Koen
authors.initials: K
authors.lastname: Demyttenaere
authors.forename: Vivette
authors.initials: V
authors.lastname: Glover
authors.forename: Bea
authors.initials: B
authors.lastname: Van den Bergh
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.forename: Stephan
authors.initials: S
authors.lastname: Claes
mesh_terms: D000328:Adult; D001007:Anxiety / Q000097:blood / Q000235:genetics / Q000523:psychology; D019540:Area Under Curve; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004644:Emotions / Q000502:physiology*; D057890:Epigenomics; D005060:Europe; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012463:Saliva / Q000378:metabolism; D011795:Surveys and Questionnaires
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone