DNA methylation age has been used in recent studies as an epigenetic marker of accelerated cellular aging, whose contribution to the brain structural changes was lately acknowledged. We aimed to characterize the association of epigenetic age (i.e. estimated DNA methylation age) and its acceleration with surface area, cortical thickness, and volume in healthy young adults. Using the multi-tissue method (Horvath S. DNA methylation age of human tissues and cell types. 2013. Genome Biol 14), epigenetic age was computed with saliva sample. Epigenetic age acceleration was derived from residuals after adjusting epigenetic age for chronological age. Multiple regression models were computed for 148 brain regions for surface area, cortical thickness, and volume using epigenetic age or accelerated epigenetic age as a predictor and controlling for sex. Epigenetic age was associated with surface area reduction of the left insula. It was also associated with cortical thinning and volume reduction in multiple regions, with prominent changes of cortical thickness in the left temporal regions and of volume in the bilateral orbital gyri. Finally, accelerated epigenetic age was negatively associated with right cuneus gyrus volume. Our findings suggest that understanding the mechanisms of epigenetic age acceleration in young individuals may yield valuable insights into the relationship between epigenetic aging and the cortical change and on the early development of neurocognitive pathology among young adults.

Despite the importance of child-caregiver interactions in child development, the association between parenting stress and the brain development of children remains unclear. We investigated how parenting stress relates to neural connectivity in the white matter structures and whether it has any associations with volume of thalamic subfields in 47 typically developing children (24 girls, mean age: 8.96 years old). While parents completed the Parenting Stress Index (PSI), children underwent diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI) scanning. The six PSI subscales reflecting child characteristics were negatively associated with the mean fractional anisotropy values of the bilateral anterior thalamic radiations (ATRs), bridging thalamus to the prefrontal cortex. Our exploratory analysis on thalamic subfields disclosed significant negative associations between the six PSI subscales and the volume of the right reuniens nuclei (MV-re) that is situated in the medial ventral thalamus and mediates interaction between the hippocampus and the prefrontal cortex. Considering a reduced white matter integrity in bilateral ATRs and smaller MV-re volume, parenting stress stemming from child-related features may reflect inefficient exchange of information via thalamocortical circuits in the developing brain. Our findings indicate the significance of interactions in child-caregiver dyads in brain development and particularly, thalamic structures.