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

Lookup NU author(s): Professor Caroline Relton

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Abstract

© 2019 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.

Publication metadata

Author(s): Dunn EC, Soare TW, Zhu Y, Simpkin AJ, Suderman MJ, Klengel T, Smith ADAC, Ressler KJ, Relton CL

Publication type: Article

Publication status: Published

Journal: Biological Psychiatry

Year: 2019

Volume: 85

Issue: 10

Pages: 838–849

Print publication date: 15/05/2019

Online publication date: 21/01/2019

Acceptance date: 16/12/2018

ISSN (print): 0006-3223

ISSN (electronic): 1873-2402

Publisher: Elsevier USA

URL: https://doi.org/10.1016/j.biopsych.2018.12.023

DOI: 10.1016/j.biopsych.2018.12.023

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