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Children under the age of 3 may be especially vulnerable to DNA methylation changes related to early adversity—changes that could have long-term consequences for their mental health, according to a new longitudinal study.

The findings of this report, "Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study," are currently available online and will appear in the May 15 print issue of Biological Psychiatry.

The primary goal of this study was to test the hypothesis that children have particularly sensitive development periods when life adversity is associated with more significant changes in DNA methylation.

"Very early appears to be a sensitive period when exposure to adversity predicts differential DNA methylation patterns," the authors wrote. This study focuses on seven early-life stressors that are associated with altered gene expression at 38 DNA methylation sites at which adverse childhood experiences (ACEs) appear to be associated with changes in methylation.

Previous studies on both humans and animals have shown that early-life adversity can have a long-lasting impact on gene expression. Additionally, these studies identified that differences in DNA methylation appear to play a vital role in enhancing or silencing gene expression. DNA methylation during the first years of life seems to change epigenetic profiles in ways that may be associated with increased risks.

"One of the major unanswered questions in child psychiatry has been, 'How do the stressors children experience in the world make them more vulnerable to mental health problems in the future?'" Erin Dunn of the Psychiatric and Neurodevelopmental Unit in the Massachusetts General Hospital Center for Genomic Medicine said in a statement. "These findings suggest that the first three years of life may be an especially important period for shaping biological processes that ultimately give rise to mental health conditions. If these results are replicated, they imply that prioritizing policies and interventions to children who experienced adversity during those years may help reduce the long-term risk for problems like ."

Below are seven early-life stressors that may relate to DNA methylation, as noted by Dunn et al.:

Abuse by a parent or other . A mother's mental illness. Living in a single-adult household. Family instability. Family financial . Neighborhood disadvantage or poverty. Physical or by anyone.

Of these seven factors, neighborhood disadvantage or poverty appeared to have the greatest association with DNA methylation, followed by family financial stress, physical or sexual abuse, and living in a single adult household.

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For this longitudinal study, the researchers tracked each participant's exposure to various stressors during specific stages of development. As mentioned, Dunn and colleagues found that childhood adversity before the age of 3 had a more significant association with DNA methylation than early-life adversity between 3-to-5 years of age or between the ages of 5 and 7.

Although experiencing stressors very early in childhood had the most significant relationship with DNA methylation, at older ages were also predictive, according to the researchers.

The data used for this study came from a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children. ALSPAC is a UK-based birth cohort study that has been tracking the psychological and physical well-being of families in the Bristol area since the early 1990s.

The new study has some limitations. In particular, the sample size is relatively small. Future studies with larger groups of participants are needed to fully understand how early-life adversity influences DNA methylation, and how these changes may influence long-term psychiatric outcomes.

"Our results need to be replicated by other investigators, and we also need to determine whether these changes in DNA methylation patterns are associated with subsequent mental health problems," Dunn said. "Only then will we be able to really understand the links between childhood adversity, DNA methylation, and the risk of mental health problems; and that understanding could guide us to better ways of preventing those problems from developing."

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