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Change in FK506 binding protein 5 (FKBP5) methylation over time among preschoolers with adversity

Published online by Cambridge University Press:  22 November 2017

Stephanie H. Parade ,
Justin Parent ,
Kantoniony Rabemananjara ,
Ronald Seifer ,
Carmen J. Marsit ,
Bao-Zhu Yang ,
Huiping Zhang  and
Audrey R. Tyrka
Stephanie H. Parade*
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Justin Parent
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital Florida International University
Kantoniony Rabemananjara
Affiliation:
E. P. Bradley Hospital
Ronald Seifer
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Carmen J. Marsit
Affiliation:
Emory University
Bao-Zhu Yang
Affiliation:
Yale University School of Medicine
Huiping Zhang
Affiliation:
Boston University School of Medicine
Audrey R. Tyrka
Affiliation:
Brown University Alpert Medical School Butler Hospital
*
Address correspondence and reprint requests to: Stephanie H. Parade, Bradley Research Center, E. P. Bradley Hospital, 1011 Veterans Memorial Parkway, East Providence, RI 02915; E-mail: Stephanie_Parade@Brown.edu.
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Abstract

FK506 binding protein 5 (FKBP5) alters stress response system functioning, and childhood maltreatment is associated with methylation of the FKBP5 gene. Yet it is unknown if maltreatment contributes to change in FKBP5 methylation over time. The current study draws upon a sample of 231 preschoolers, including 123 with child welfare documentation of moderate to severe maltreatment in the past 6 months, to understand if maltreatment contributes to change in FKBP5 methylation over a 6-month period. Review of child protection records and semistructured interviews in the home were used to assess maltreatment and exposure to other contextual stressors, as well as service utilization. Methylation of FKBP5 at two CpG sites in intron 7 was measured from saliva DNA at the time of initial study enrollment, and 6 months following enrollment. Child maltreatment was associated with change in FKBP5 methylation over time, but only when children were exposed to high levels of other contextual stressors. Service utilization was associated with increases in methylation over time, but only among children with the FKPB5 rs1360780 protective CC genotype. Methylation of FKBP5 is sensitive to stress exposure and may be a mechanism linking early adversity to long-term health and developmental outcomes.

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. 1627 - 1634
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

This research was supported by Grant R01 MH083704 awarded to the last author 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 the genotyping array 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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