Associations of depression and anxiety symptoms in childhood and adolescence with epigenetic aging

Background: Childhood anxiety and depression symptoms are potential risk factors for accelerated biological aging. In child and adolescent twins, we tested whether these symptoms were associated with DNA methylation (DNAm) aging, a measure of biological aging. Methods: 276 twins (135 pairs, 6 singletons) had DNAm assayed from saliva in middle childhood (mean = 7.8 years). Residuals of five different DNAm age estimates regressed on chronological age were used to indicate accelerated aging. Anxiety and depression symptoms were assessed in middle childhood and early adolescence using the Child Behavior Checklist. Mixed effect regression was used to examine potential relationships between anxiety or depression symptoms, and accelerated DNAm age. MZ twin difference analysis was then utilized to determine if associations were environmentally-driven or due to genetic or shared-environment confounding. Results: Anxiety and depression symptoms were not associated with accelerated DNAm aging in middle childhood. In early adolescence, only the Wu clock was significant and indicated that each one symptom increase in anxiety symptoms had an associated age acceleration of 0.03 years (similar to 0.4 months; p = 0.019). MZ twin difference analysis revealed non-significant within-pair effects, suggesting genetic and shared environmental influences. Limitations: Sample is predominantly male and white. Generalizability to other populations may be limited. Conclusion: Accelerated DNAm aging of the Wu clock in middle childhood is associated with anxiety, but not depression, symptoms in early adolescence. Further, this association may be the result of shared genetic and environmental influences. Accelerated DNAm aging may serve as an early risk factor or predictor of later anxiety symptoms.