The DOI matches its Crossref record; 118 of the 118 references it cites were found in a registry or an index.
Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5)
Open accessAbstract
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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“Polygenic scores for Environmental Sensitivity have been shown to moderate the beneficial outcomes of cognitive behavioural therapy on anxiety symptoms,89 and genome-wide and single locus variation in the SCL6A4 gene the impact of good parenting quality on youth psychopathology.89,90”
From The role of epigenetics in psychological resilience (2021) · cites this paper as [89]
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Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 5,429 · cited 1×
“Excessive activation of the HPA axis over time or in response to extreme stress may result in downregulation of this system (Fries, Hesse, Hellhammer, & Hellhammer, 2005; Heim, Ehlert, & Hellhammer, 2000; McEwen, 2007; Pryce et al., 2005; Tyrka et al., 2008).”
BackgroundStress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621
Norman, R. E., Byambaa, M., De, R., Butchart, A., Scott, J., & Vos, T. (2012) · PLoS Medicine · doi:10.1371/journal.pmed.1001349 · Cited by 3,387
Heim, C. (2000) · JAMA · doi:10.1001/jama.284.5.592 · Cited by 1,968
Stability and flexibility of epigenetic gene regulation in mammalian development
Reik, W. (2007) · Nature · doi:10.1038/nature05918 · Cited by 1,963 · cited 2×
“be the most stable form of epigenetic alteration (Reik, 2007).”
BackgroundThe potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders
Heim, C., Ehlert, U., & Hellhammer, D. H. (2000) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(99)00035-9 · Cited by 1,688
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Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., Pace, T. W. W., Mercer, K. B., Mayberg, H. S., Bradley, B., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3275 · Cited by 1,447
Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons
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Research works printed but not linked: 1
- Barnett, 1993, Child abuse, child development, and social policy, 7
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Matosin, N., Halldorsdottir, T., & Binder, E. B. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.01.021 · Cited by 226
Argentieri, M. A., Nagarajan, S., Seddighzadeh, B., Baccarelli, A., & Shields, A. E. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.03.044 · Cited by 199
Parade, S. H., Huffhines, L. P., Daniels, T. E., Stroud, L. R., Nugent, N. R., & Tyrka, A. R. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01207-y · Cited by 192
Self-citationChildhood maltreatment and DNA methylation: A systematic review
Cecil, C. A. M., Zhang, Y., & Nolte, T. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.019 · Cited by 186
Epigenetic programming by stress and glucocorticoids along the human lifespan
Zannas, A. S., & Chrousos, G. P. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.35 · Cited by 158
Metadata
- 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
- 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
- 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
- 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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