The DOI matches its Crossref record; 92 of the 92 references it cites were found in a registry or an index.
Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study
Open accessPublished version of a preprint
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Early life is a special period characterized by a high level of plasticity and fast development (76).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [76]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“recent clinical studies demonstrate that the developmental timing of childhood adversity, with sensitive periods before three years of age, explains more variability in DNA methylation than the accumulation or recency of exposure.39”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [39]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Epigenetics can regulate neuronal plasticity and memory consolidation.38–41”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [39]
Experimental — accuracy not yet measuredIn the citing paper
“Time since adversity can moderate the magnitude of epigenetic change,53 while repeated or varied sources of adversity may accumulate to produce larger epigenetic responses.54,55”
From The role of epigenetics in psychological resilience (2021) · cites this paper as [53]
In the citing paper
“It has been suggested that the timing of adversity explains more variability in DNA methylation than the accumulation or recency of exposure [216].”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [216]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587
Efron, B., Hastie, T., Johnstone, I., & Tibshirani, R. (2004) · The Annals of Statistics · doi:10.1214/009053604000000067 · Cited by 9,357
Child abuse: Adolescent records vs. adult recall
Femina, D. D., Yeager, C. A., & Lewis, D. O. (1990) · Child Abuse & Neglect · doi:10.1016/0145-2134(90)90033-p · Cited by 8,820
Burden and consequences of child maltreatment in high-income countries
Gilbert, R., Widom, C. S., Browne, K., Fergusson, D., Webb, E., & Janson, S. (2009) · The Lancet · doi:10.1016/s0140-6736(08)61706-7 · Cited by 3,876
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
Ben-Shlomo, Y. (2002) · International Journal of Epidemiology · doi:10.1093/ije/31.2.285 · Cited by 3,038
Boyd, A., Golding, J., Macleod, J., Lawlor, D. A., Fraser, A., Henderson, J., Molloy, L., Ness, A., Ring, S., & Davey Smith, G. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dys064 · Cited by 2,996
Hammen, C. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143938 · Cited by 2,979
Risky families: Family social environments and the mental and physical health of offspring
Repetti, R. L., Taylor, S. E., & Seeman, T. E. (2002) · Psychological Bulletin · doi:10.1037/0033-2909.128.2.330 · Cited by 2,884
Research works printed but not linked: 1
- Widom, 2007, Child abuse and neglect: Potential derailment from normal developmental pathways, NYS Psychologist, 19, 2
Cited by
Sorted by citations
Nelson, C. A., & Gabard-Durnam, L. J. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.01.002 · Cited by 501
Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma
Jiang, S., Postovit, L., Cattaneo, A., Binder, E. B., & Aitchison, K. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00808 · Cited by 288
Biological embedding of experience: a primer on epigenetics
Aristizabal, M. J., Anreiter, I., Halldorsdottir, T., Odgers, C. L., McDade, T. W., Goldenberg, A., Mostafavi, S., Kobor, M. S., Binder, E. B., Sokolowski, M. B., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820838116 · Cited by 268
Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246
Lees, B., Mewton, L. R., Jacobus, J., Valadez, E. A., Stapinski, L. A., Teesson, M., Tapert, S. F., & Squeglia, L. M. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.20010086 · Cited by 198
Metadata
- 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
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 85
- Issue
- 10
- Pages
- 838-849
- ISSN
- 0006-3223 (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
