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Early-life stress not linked to changes in DNA methylation

Epigenetic changes seen in DNA methylation were not linked to victimization stress levels in young people, according to an epidemiological analysis published in The American Journal of Psychiatry.

“Although a substantial body of research has accumulated linking early-life adversity to differences in DNA methylation, methods and results are heterogeneous and nonoverlapping,” Sarah J. Marzi, PhD, from the Blizard Institute, Queen Mary University of London, and colleagues wrote. “Observational studies have struggled to disentangle the effects of stress exposure from confounding effects of other toxins (eg, tobacco smoking) and a host of other environmental (eg, poverty) and genetic factors known to be correlated with stress exposure. More investigation of the link between stress exposure and DNA methylation is needed.”

Using data from the Environmental Risk (E-Risk) Longitudinal Twin Study, researchers examined the link between early-life victimization and whole-blood DNA methylation among 2,232 British twins. At ages 5, 7, 10, 12 and 18 years, they conducted home visits and assessed childhood physical, sexual and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-bullying; and crime. At age 18, they assessed teen victimization from age 12 to 18 years via interview-administered questionnaire.

Epigenetic analyses showed that multiple types of childhood and teenage victimization had few significant associations with variation in DNA methylation at age 18 years. Although victimized teens were more likely to smoke tobacco and to have smoked more pack-years, which can affect DNA methylation, when researchers added smoking pack-years as a covariate, it did not remain significantly associated with victimization. According to Marzi and colleagues, methylation associations identified for victimization overlapped with those detected for tobacco smoking, making it hard to separate biological effects of psychosocial influences from those for health behaviors linked to victimization. Furthermore, the few methylation associations identified for victimization did not replicate across different specifications of victimization stress.

“Our conclusion is not that DNA methylation is unimportant. Rather, it is that observational studies using free-ranging humans, relying on peripheral tissue, and using currently available high-throughput technologies appear to yield weak and inconsistent evidence on the epigenetics of early-life stress,” Marzi and colleagues wrote. “We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to nonhuman experimental models in uncovering how stress gets under the skin in humans.” – by Savannah Demko

Disclosures: Marzi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.