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      Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links with Internalizing Behavior Problems

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          Abstract

          Accumulating evidence suggests that early adversity is linked to methylation of the glucocorticoid receptor gene NR3C1, which is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis. Yet no prior work has considered the contribution of methylation of NR3C1 to emerging behavior problems and psychopathology in childhood. The current study examined links between methylation of NR3C1 and behavior problems in preschoolers. Data were drawn from a sample of preschoolers with early adversity (n=171). Children ranged in age from 3 to 5 years, were racially and ethnically diverse, and nearly all qualified for public assistance. Seventy-one children had child welfare documentation of moderate-severe maltreatment in the past six months. Structured record review and interviews in the home were used to assess early adversity. Parents reported on child internalizing and externalizing behavior problems. Methylation of NR3C1 at exons 1 D, 1 F, and 1 H were measured via sodium bisulfite pyrosequencing from saliva DNA. Methylation of NR3C1 at exons 1 D and 1 F was positively associated with internalizing ( r = .21, p < .01 and r = .23, p < .01 respectively), but not externalizing, behavior problems. Furthermore, NR3C1 methylation mediated effects of early adversity on internalizing behavior problems. These results suggest that methylation of NR3C1 contributes to psychopathology in young children, and NR3C1 methylation from saliva DNA is salient to behavioral outcomes.

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          Author and article information

          Journal
          0372725
          2917
          Child Dev
          Child Dev
          Child development
          0009-3920
          1467-8624
          25 November 2015
          January 2016
          01 January 2017
          : 87
          : 1
          : 86-97
          Affiliations
          [a ]Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, East Providence, RI, USA
          [b ]Bradley/Hasbro Children’s Research Center, E. P. Bradley Hospital, East Providence, RI, USA
          [c ]Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA
          [d ]Department of Pharmacology and Toxicology, Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
          Author notes
          Article
          PMC4869528 PMC4869528 4869528 nihpa740000
          10.1111/cdev.12484
          4869528
          26822445
          d09ab009-ce11-4ae7-a007-3b5c3270b1a9
          History
          Categories
          Article

          internalizing problems,preschool,glucocorticoid receptor,methylation,adversity

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