Intra-individual methylomics detects the impact of early-life adversity

Abstract

Genetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an 'epigenetic signature' of earlylife experiences. Here, we employed a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular-metabolic enzymes, ion channels and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate related transcription factors, indicating their potential upregulation. Thus, intraindividual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth and function.

The Developmental Origins of Opioid Use Disorder and Its Comorbidities

“…The risk factors for OUD are numerous and complex, and genetics (Kreek et al, 2012;Crist et al, 2019;Jiang et al, 2019), drug availability (Volkow et al, 2011;Wright et al, 2014), and environmental factors such as early life adversity (ELA; Dube et al, 2003;Sinha, 2008;Kreek et al, 2012) all play a role. ELA related to poverty, trauma and chaotic environment affects over 30% of children in the U.S. (American Psychological Association, 2018).…”