title: The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior.
abstract: Exposure to maternal mood disorder in utero may program infant neurobehavior via DNA methylation of the glucocorticoid receptor (NR3C1) and 11β-hydroxysteroid dehydrogenase type 2 ( 11β-HSD-2), two placental genes that have been implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA) axis. We tested the relations among prenatal exposure to maternal depression or anxiety, methylation of exon 1F of NR3C1 and 11β-HSD-2, and newborn neurobehavior. Controlling for relevant covariates, infants whose mothers reported depression during pregnancy and showed greater methylation of placental NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than infants whose mothers did not report depression. On the other hand, infants whose mothers reported anxiety during pregnancy and showed greater methylation of placental 11β-HSD-2 CpG4 were more hypotonic compared with infants of mothers who did not report anxiety during pregnancy. Our results support the fetal programming hypothesis and suggest that fetal adjustments to cues from the intrauterine environment, in this case an environment that could be characterized by increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.
authors.affiliation: Brown Center for the Study of Children at Risk; Department of Pediatrics; Women & Infants Hospital of Rhode Island; Providence, RI USA; Department of Psychiatry; Warren Alpert Medical School of Brown University; Providence, RI USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Conradt
authors.affiliation: Brown Center for the Study of Children at Risk; Department of Pediatrics; Women & Infants Hospital of Rhode Island; Providence, RI USA; Department of Psychiatry; Warren Alpert Medical School of Brown University; Providence, RI USA; Department of Pediatrics; Warren Alpert Medical School of Brown University; Providence, RI USA.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Lester
authors.affiliation: Department of Community and Family Medicine; Section of Biostatistics and Epidemiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Appleton
authors.affiliation: Department of Community and Family Medicine; Section of Biostatistics and Epidemiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Armstrong
authors.affiliation: Department of Community and Family Medicine; Section of Biostatistics and Epidemiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001007:Anxiety / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D003863:Depression / Q000235:genetics / Q000378:metabolism; D005260:Female; D047109:Fetal Development; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D018730:Infant Behavior; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone
keywords: DNA methylation; maternal anxiety; maternal depression; newborn neurobehavior