Journal Article Annotations
2024, 4th Quarter
Annotations by Zachary Harvanek, MD, PhD
January, 2025
The finding:
In this study, the authors found that, in a study of Syrian children, exposure to war was associated with differential methylation, but not at sites that had been previously linked to childhood trauma. Sex-specific analyses revealed differentially-methylated regions that had previously been associated with aging, gulf war illness, and neuronal development. Further analyses investigating epigenetic aging found no differences after correction for multiple comparisons, with nominal associations suggesting war exposure was associated with decreased epigenetic age in some clocks.
Strength and weaknesses:
Strengths of this study include a large sample size, detailed assessment of war exposure using the War Events Questionnaire, and analyses of multiple clocks (including pediatric-specific clocks) for associations with war. A notable limitation of the study is the use of salivary DNA for epigenetic clock analyses, whereas DNA from blood samples is considered to be the gold standard, as well as the larger percentage of children who had experienced any war exposure (97%), which could limit the potential comparison group.
Relevance:
These findings suggest that war exposure may have distinct impacts on DNA methylation, which may be separate from general childhood trauma. The authors suggest that the nominal age deceleration may be associated with delayed development in adolescents exposed to war, although notably they do not have specific data on development in their study.
The finding:
In this study, the authors examine the relationship between multiple factors (including psychiatric symptoms) and epigenetic aging, as measured seemingly by their own, newly developed clock. The authors suggest that there is a “lagged” effect of depressive symptoms, whereby depression does not cause immediate age acceleration, but instead depression now leads to accelerated age at a later timepoint. Notably, this lagging association between depression and epigenetic age remained significant even after correcting for BMI, smoking, cannabis, and alcohol use.
Strength and weaknesses:
The longitudinal design of this study, with epigenetic age measured in both childhood and adulthood, was a clear strength of this study, as was the attempt to adjust for potential confounding factors (e.g., BMI, smoking, substance use). A notable difference in this paper is that they did not use traditional methylation array platforms, but instead sequencing-based DNA methylation data, which led to them feeling it was necessary to develop their own clock. This does lead to a limitation of external validity, as this clock has not been clearly established and linked to health concerns yet.
Relevance:
These findings suggest that depressive symptoms may have lasting effects later in life. While the authors did not assess for treatment of psychiatric symptoms, it would be reasonable to hypothesize that, if depressive symptoms have a lagged effect on epigenetic aging, then prompt treatment may be able to mitigate some of those effects (though of course, more studies would be needed to demonstrate this).