Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study

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.

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 (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced 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 Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=691-774).

Results: After covariate adjustment and multiple testing correction, we identified 38 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=35) were predicted by the timing of adversity, namely exposures before age 3. Neither the
accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS 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 vs. unexposed to “early life” adversity may dilute observed effects.

• Journal Article Type: Article
• Acceptance Date: Dec 16, 2018
• Online Publication Date: Jan 21, 2019
• Publication Date: May 15, 2019
• Deposit Date: Jan 16, 2019
• Publicly Available Date: Jan 22, 2020
• Journal: Biological Psychiatry
• Print ISSN: 0006-3223
• Electronic ISSN: 1873-2402
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 85
• Issue: 10
• Pages: 838-849
• DOI: https://doi.org/10.1016/j.biopsych.2018.12.023
• Keywords: epigenetics, DNA methylation, childhood adversity, sensitive periods children, longitudinal
• Public URL: https://uwe-repository.worktribe.com/output/853533
• Publisher URL: https://doi.org/10.1016/j.biopsych.2018.12.023
• Additional Information: Additional Information : This is the author's accepted manuscript. The final published version is available here: https://doi.org/10.1016/j.biopsych.2018.12.023.
• Contract Date: Jan 16, 2019