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Methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), in maltreated and nonmaltreated children: Associations with behavioral undercontrol, emotional lability/negativity, and externalizing and internalizing symptoms

  • Dante Cicchetti (a1) (a2) and Elizabeth D. Handley (a2)


The present study examined the effect of various dimensions of child maltreatment (i.e., developmental timing of maltreatment, number of maltreatment subtypes, and chronicity of maltreatment) on methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), and investigated the associations between NR3C1 methylation and child outcomes. Participants included 534 children who attended a research summer camp program for school-aged maltreated (53.4%) and nonmaltreated (46.6%) children from low socioeconomic backgrounds. Results show that children with early onset maltreatment evidence significant hypermethylation compared to nonmaltreated children. Moreover, more maltreatment subtypes experienced and more chronic maltreatment are both related to greater NR3C1 hypermethylation. Findings also indicate that hypermethylation of NR3C1 is linked with a number of negative child outcomes including greater emotional lability–negativity, higher levels of ego undercontrol, more externalizing behavior, and greater depressive symptoms. Together, results highlight the role of methylation of NR3C1 in the effects of child maltreatment on the development of emotion dysregulation and psychopathology.


Corresponding author

Address correspondence and reprint requests to: Dante Cicchetti, Institute of Child Development, University of Minnesota, 51 East River Parkway, Minneapolis, MN 55455; E-mail:; or Elizabeth D. Handley, Mt. Hope Family Center, University of Rochester, 187 Edinburgh Street, Rochester, NY 14608; E-mail:


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We are grateful for the research support provided by the Emerald Foundation, Inc., and the Jacobs Foundation to Dante Cicchetti, and the National Institute of Mental Health (R01-MH83979 to D.C.).



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