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Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

Published online by Cambridge University Press:  22 November 2017

Justin Parent ,
Stephanie H. Parade ,
Laura E. Laumann ,
Kathryn K. Ridout ,
Bao-Zhu Yang ,
Carmen J. Marsit ,
Ronald Seifer  and
Audrey R. Tyrka
Justin Parent
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital Florida International University
Stephanie H. Parade
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Laura E. Laumann
Affiliation:
Butler Hospital
Kathryn K. Ridout
Affiliation:
Brown University Alpert Medical School Butler Hospital
Bao-Zhu Yang
Affiliation:
Yale University School of Medicine
Carmen J. Marsit
Affiliation:
Emory University
Ronald Seifer
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Audrey R. Tyrka*
Affiliation:
Brown University Alpert Medical School Butler Hospital
*
Address correspondence and reprint requests to: Audrey R. Tyrka, Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02903; E-mail: audrey_tyrka@brown.edu.
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Abstract

Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus–pituitary–adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3–5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.

Type
Special Issue Articles
Information
Development and Psychopathology , Volume 29 , Special Issue 5: Biological and Behavioral Effects of Early Adversity on Multiple Levels of Development , December 2017 , pp. 1635 - 1648
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

This research was supported by Grant R01 MH083704 (to A.R.T.) and R25 MH101076 (K.K.R.) from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIMH. We are grateful to the children and families who participated in this study, and we thank Hasbro Children's Hospital, Rhode Island Head Start, and the Rhode Island Department of Children, Youth, and Families for assisting in recruitment of study participants. We also thank Brittney Josefson and the numerous other research assistants who contributed to this project, and Asi Polly Gobin for data management. Isolation of DNA and genotyping were done in the laboratory of Joel Gelernter, MD, and we are grateful to Dr. Gelernter and his staff for their contribution.

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