Cited by 315Epigenetics and DNA MethylationChild Abuse and TraumaMaternal Mental Health During Pregnancy and Postpartum

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Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study

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Dunn, Erin C., Soare, Thomas W., Zhu, Yiwen, Simpkin, Andrew J., Suderman, Matthew J., Klengel, Torsten, Smith, Andrew D.A.C., Ressler, Kerry J., Relton, Caroline L.·2019·Biological Psychiatry

DOI 10.1016/j.biopsych.2018.12.023PMC PMC6552666

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Abstract

Background Exposure to early-life adversity is known to predict DNA methylation (DNAm) patterns that may be related to psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure.Methods Using a two-stage structured life course modeling approach, we tested the hypothesis that there are sensitive periods when adversity induces greater DNAm changes. We tested this hypothesis in relation to two alternatives: an accumulation hypothesis, in which the effect of adversity increases with the number of occasions exposed, regardless of timing; and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomic Studies, a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (n = 691-774).Results After covariate adjustment and multiple testing correction, we identified 38 CpG sites that were differentially methylated at 7 years of age following exposure to adversity. Most loci (n = 35) were predicted by the timing of adversity, namely exposures before 3 years of age. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard epigenome-wide association study of lifetime exposure (vs. no exposure) failed to detect these associations.Conclusions The developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Very early childhood appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed versus unexposed to early-life adversity may dilute observed effects.

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Authors: Dunn, E. C., Soare, T. W., Zhu, Y., Simpkin, A. J., Suderman, M. J., Klengel, T., Smith, A. D. A. C., Ressler, K. J., & Relton, C. L.
Affiliations: Broad Institute (US)
Massachusetts General Hospital (US)
University of Bristol (GB)
Harvard University (US)
University of the West of England (GB)
Corresponding author: Dunn, Erin C.
ORCID: Dunn, Erin C.
Soare, Thomas W.
Zhu, Yiwen
Simpkin, Andrew J.
Suderman, Matthew J.
Klengel, Torsten
Smith, Andrew D.A.C.
Ressler, Kerry J.
Relton, Caroline L.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2019-05
Volume: 85
Issue: 10
Pages: 838-849
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2018.12.023
PMC: PMC6552666
OpenAlex: W2950440677
Cited by: 315
References: 92
Citations by year: 2026: 25 · 2025: 35 · 2024: 36 · 2023: 41 · 2022: 36 · 2021: 39 · 2020: 80 · 2019: 20
FWCI: 14.48
Type: journal article
Language: en
Open access: green
doi.org
Licence: cc-by-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biological Psychiatry (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
UWE Research Repository (UWE Bristol) (acceptedVersion, cc-by-nc-nd)
Explore Bristol Research (acceptedVersion, cc-by-nc-nd)
UWE Research Repository (UWE Bristol) (submittedVersion, cc-by-nc-nd)
GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Bristol Research (University of Bristol) (submittedVersion, cc-by-nc-nd)
Newcastle University ePrints (Newcastle Univesity)
Funders: Medical Research Council
National Center for Research Resources
Biotechnology and Biological Sciences Research Council (BB/I025263/1, BBI025751/1, MC_UU_12013/2, MC_UU_12013/8)
National Center for Advancing Translational Sciences
Economic and Social Research Council
Harvard University
University of Bristol
Harvard Catalyst
Wellcome Trust (102215/2/13/2)
National Institutes of Health (K01MH102403, R01MH113930, UL1 TR001102)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Keywords: childhood adversity, DNA methylation, sensitive period, early childhood, differentially methylated CpG sites, mother-child pairs, epigenome-wide association study, psychiatric risk
MeSH terms: Adverse Childhood Experiences, Epigenome, Child, Child, Preschool, Female, Humans, Infant, Longitudinal Studies, Male, Parent-Child Relations, Prospective Studies, Time Factors, CpG Islands, DNA Methylation, Epigenesis, Genetic

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Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study

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