Epigenetic age across development in children and adolescents with ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition, though symptoms vary both within and between people in the population. We aimed to investigate trajectories of individual biological aging through the change in residuals of DNA methylation age estimates (EpiAge) regressed on chronological age (EpiAge Gap) in children and adolescents with and without ADHD.

Three well-established epigenetic clocks (PedBE, Horvath, and Skin & blood) were used to estimate EpiAge in 293 saliva samples from 169 participants (91 with ADHD symptoms) from the Neuroimaging of the Children's Attention Project (NICAP). Participants attended single (cross-sectional sample, n = 75) or multiple (2-3) waves of assessment (longitudinal sample, n = 94). We compared EpiAge Gap between ADHD and control groups cross-sectionally and longitudinally, and replicated these findings in a second pediatric cohort from the Oregon ADHD-1000 cohort.

Across all three clocks, EpiAge Gap was comparable between ADHD and controls from the cross-sectional sample, and was a null finding for our longitudinal analysis of change in EpiAge Gap, after FDR correction (pFDR=0.24). Both cross-sectional and longitudinal findings were consistent in the replication cohort.

This study found no strong evidence of differential epigenetic aging in developing children and adolescents with or without ADHD. Larger cohort studies, which utilize estimates over a prolonged duration, crossing both early and later developmental periods, would further our understanding of biological age in ADHD.