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Cited by 128Child Abuse and TraumaEpigenetics and DNA MethylationStress Responses and Cortisol

Epigenetic modifications of the glucocorticoid receptor gene are associated with the vulnerability to psychopathology in childhood maltreatment

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Radtke, K M, Schauer, M, Gunter, H M, Ruf-Leuschner, M, Sill, J, Meyer, A, Elbert, T·2015·Translational Psychiatry
DOI 10.1038/tp.2015.63PMC PMC4471294
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Abstract

Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic-pituitary-adrenal axis--in particular, the glucocorticoid receptor (hGR) gene--stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.

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  • A CpG island in NR3C1 exon 1F is the only genomic region with a significant positive correlation between the degree of methylation and the number of childhood adversities and with BPD and MDD symptoms.

    “highlighting a CpG island in exon 1 F as the only genomic region with a significant positive correlation between the degree of methylation and the number of childhood adversities on the one hand and with BPD and MDD symptoms on the other hand (Radtke et al., 2015)”

    From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Radtke et al., 2015

    The Results section reports that methylation at cg17860381 in exon 1F was significantly positively correlated with childhood adversities and BPD symptoms. Its positive correlation with depression symptoms only approached statistical significance; a different CpG site, cg26464411, had a statistically significant correlation with depression symptoms. Thus the claim overstates the exon 1F finding for MDD symptoms. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • In a prediction model, the number of experienced childhood adversities, a combined principal component of NR3C1 exon 1 and 2 methylation, and their interaction all had significant predictive potential for future psychopathology.

    “the number of experienced childhood adversities, a combined principal component of NR3C1 exon 1 and 2 methylation and their interaction, all had significant predictive potential”

    From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Radtke et al., 2015

    The Results section (‘Relationship between hGR methylation, childhood abuse and psychological ill-health’; page unavailable) reports that childhood-adversity count, a principal component of hGR methylation, and their interaction were all significant predictors of psychological ill-health. The principal component comprised nine CpG sites, not a specified combination of exon 1 and 2 methylation. The paper assessed psychological health at the time of the study; it did not test prediction of future psychopathology. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • When evaluating the effect of childhood adversity and exon 1F methylation alone on the development of BPD symptoms, only significant main effects, but no interaction effect, were found.

    “when evaluating the effect of childhood adversity and exon 1 F methylation alone on the development of BPD symptoms, only significant main effects, yet no interaction effect, were found”

    From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Radtke et al., 2015

  • NR3C1 methylation is associated with an increased number of childhood adversities.

    “↑ NR3C1 methylation associated with increased number of childhood adversities”

    From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Radtke et al., 2015

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Research works printed but not linked: 1

  1. Teicher MH Parigger A Modified Adverse Childhood Experience Scale, version 0.9; inspired by the ACE Scale Neuner F Elbert Teds). A Short-Term Intervention for Traumatic Stressvol. 2. Huber Publishers & Hogrefe: Cambridge, MA, USA/Göttingen, Germany 2011

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Authors
Radtke, K. M., Schauer, M., Gunter, H. M., Ruf-Leuschner, M., Sill, J., Meyer, A., & Elbert, T.
Affiliations
University of Konstanz (DE)
Corresponding author
Radtke, K M
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2015-05-26
Volume
5
Issue
5
Pages
e571-e571
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2015.63
PMC
PMC4471294
OpenAlex
W1520957638
Cited by
128
References
56
Citations by year
2026: 6 · 2025: 7 · 2024: 7 · 2023: 13 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 24 · 2018: 16 · 2017: 13 · 2016: 12 · 2015: 3
FWCI
18.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KOPS (University of Konstanz) (submittedVersion, cc-by)
Funders
  • Medical Research Council (MR/K001744/1)
  • Biotechnology and Biological Sciences Research Council (BBS/E/D/20310000)
  • Natural Environment Research Council (NBAF010003)
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
glucocorticoid receptor, DNA methylation, child abuse, early life stress, borderline personality disorder, psychopathology, hypothalamic-pituitary-adrenal axis, lymphocytes, epigenetic vulnerability
MeSH terms
Adolescent, Anxiety, Mental Disorders, Borderline Personality Disorder, Child, Child Abuse, Depression, Female, Humans, Male, Receptors, Glucocorticoid, Cohort Studies, DNA Methylation, Attention Deficit and Disruptive Behavior Disorders, Genetic Predisposition to Disease, Epigenesis, Genetic, Adult Survivors of Child Abuse, Young Adult, Gene-Environment Interaction

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