Cited by 118Child Abuse and TraumaEpigenetics and DNA MethylationStress Responses and Cortisol

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Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5)

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Tyrka, Audrey R., Ridout, Kathryn K., Parade, Stephanie H., Paquette, Alison, Marsit, Carmen J., Seifer, Ronald·2015·Development and Psychopathology

DOI 10.1017/s0954579415000991PMC PMC4870720

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Abstract

A growing body of evidence suggests that alterations of the stress response system may be a mechanism by which childhood maltreatment alters risk for psychopathology. FK506 binding protein 51 (FKBP5) binds to the glucocorticoid receptor and alters its ability to respond to stress signaling. The aim of the present study was to examine methylation of the FKBP5 gene (FKBP5), and the role of an FKBP5 genetic variant, in relation to childhood maltreatment in a sample of impoverished preschool-aged children. One hundred seventy-four families participated in this study, including 69 with child welfare documentation of moderate to severe maltreatment in the past 6 months. The children, who ranged in age from 3 to 5 years, 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 two sites in intron 7 of FKBP5 was measured via sodium bisulfite pyrosequencing. Maltreated children had significantly lower levels of methylation at both CpG sites (p < .05). Lifetime contextual stress exposure showed a trend for lower levels of methylation at one of the sites, and a trend for an interaction with the FKBP5 polymorphism. A composite adversity variable was associated with lower levels of methylation at one of the sites as well (p < .05). FKBP5 alters glucocorticoid receptor responsiveness, and FKBP5 gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.

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“…of adults with a history of early life stress show attenuated cortisol response to stress (Carpenter et al., 2007, 2009; Carpenter, Shattuck, Tyrka, Geracioti, & Price, 2011; Elzinga et al., 2008; Klaassens et al., 2009), suggesting that the physiologic effects of maltreatment are long lasting.”
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Self-citation
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Authors: Tyrka, A. R., Ridout, K. K., Parade, S. H., Paquette, A., Marsit, C. J., & Seifer, R.
Affiliations: Brown University (US)
Dartmouth College (US)
Corresponding author: Tyrka, Audrey R.
ORCID: Tyrka, Audrey R.
Ridout, Kathryn K.
Parade, Stephanie H.
Paquette, Alison
Marsit, Carmen J.
Seifer, Ronald
Venue: Development and Psychopathology
Publisher: Cambridge University Press (CUP)
Published: 2015-11
Volume: 27
Issue: 4pt2
Pages: 1637-1645
ISSN: 0954-5794 (ISSN-L)
1469-2198
DOI: 10.1017/s0954579415000991
PMC: PMC4870720
OpenAlex: W2163901153
Cited by: 118
References: 118
Citations by year: 2026: 6 · 2025: 15 · 2024: 10 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 16 · 2016: 7
FWCI: 14.07
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.cambridge.org/core/terms (unspecified, 3 d)
Locations: Development and Psychopathology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R25MH101076, R01MH083704)
Topics: Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: child abuse, FKBP5, DNA methylation, glucocorticoid receptor, epigenetics, contextual stress, adversity exposure, preschool children, child welfare, psychopathology risk, stress system
MeSH terms: Tacrolimus Binding Protein 5, Child Abuse, Child, Preschool, Female, Humans, Male, Polymorphism, Genetic, Poverty, Risk, Stress, Psychological, DNA Methylation, Tacrolimus Binding Proteins

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Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5)

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