title: Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: preliminary findings in healthy adults.
abstract: BACKGROUND
  A history of early adverse experiences is an important risk factor for adult psychopathology. Changes in stress sensitivity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the association between stress and risk for psychiatric disorders. Preclinical work in rodents has linked low levels of maternal care to increased methylation of the promoter region of the glucocorticoid receptor (GR) gene, as well as to exaggerated hormonal and behavioral responses to stress. Recent studies have begun to examine whether early-life stress leads to epigenetic modifications of the GR gene in humans.
  
  
  METHODS
  We examined the degree of methylation of a region of the promoter of the human GR gene (NR3C1) in leukocyte DNA from 99 healthy adults. Participants reported on their childhood experiences of parental behavior, parental death or desertion, and childhood maltreatment. On a separate day, participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, a standardized neuroendocrine challenge test.
  
  
  RESULTS
  Disruption or lack of adequate nurturing, as measured by parental loss, childhood maltreatment, and parental care, was associated with increased NR3C1 promoter methylation (p<.05). In addition, NR3C1 promoter methylation was linked to attenuated cortisol responses to the Dex/CRH test (p<.05).
  
  
  CONCLUSIONS
  These findings suggest that childhood maltreatment or adversity may lead to epigenetic modifications of the human GR gene. Alterations in methylation of this gene could underlie the associations between childhood adversity, alterations in stress reactivity, and risk for psychopathology.
authors.affiliation: Laboratory for Clinical Neuroscience, Mood Disorders Research Program, Butler Hospital, Providence, Rhode Island, United States of America. Audrey_Tyrka@Brown.edu
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Tyrka
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Price
authors.forename: Carmen
authors.initials: C
authors.lastname: Marsit
authors.forename: Oakland C
authors.initials: OC
authors.lastname: Walters
authors.forename: Linda L
authors.initials: LL
authors.lastname: Carpenter
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001483:Base Sequence; D002648:Child; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D006262:Health; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009452:Neuroendocrinology; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone