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Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children

Published online by Cambridge University Press:  06 May 2015

Audrey R. Tyrka ,
Stephanie H. Parade ,
Nicole M. Eslinger ,
Carmen J. Marsit ,
Corina Lesseur ,
David A. Armstrong ,
Noah S. Philip ,
Brittney Josefson  and
Ronald Seifer
Audrey R. Tyrka*
Affiliation:
Butler Hospital Brown University Alpert Medical School
Stephanie H. Parade
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Nicole M. Eslinger
Affiliation:
Butler Hospital
Carmen J. Marsit
Affiliation:
Geisel School of Medicine at Dartmouth
Corina Lesseur
Affiliation:
Geisel School of Medicine at Dartmouth
David A. Armstrong
Affiliation:
Geisel School of Medicine at Dartmouth
Noah S. Philip
Affiliation:
Butler Hospital Brown University Alpert Medical School
Brittney Josefson
Affiliation:
E. P. Bradley Hospital
Ronald Seifer
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
*
Address correspondence and reprint requests to: Audrey R. Tyrka, Butler Hospital, 345 Blackstone Boulevard, Providence, RI 02906; E-mail: Audrey_Tyrka@brown.edu.
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Abstract

Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic–pituitary–adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n = 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.

Type
Regular Articles
Information
Development and Psychopathology , Volume 27 , Special Issue 2: Neural Plasticity, Sensitive Periods, and Psychopathology , May 2015 , pp. 577 - 585
Copyright
Copyright © Cambridge University Press 2015 

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