The Impact of Childhood Mental Health and Substance Use on Methylation Aging Into Adulthood.

Objective: To test whether childhood mental health symptoms, substance use, and early adversity accelerate the rate of DNA methylation (DNAm) aging from adolescence to adulthood.

Method: DNAm was assayed from blood samples in 381 participants in both adolescence (mean [SD] age = 13.9 [1.6] years) and adulthood (mean [SD] age = 25.9 [2.7] years). Structured diagnostic interviews were completed with participants and their parents at multiple childhood observations (1,950 total) to assess symptoms of common mental health disorders (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, anxiety, and depression) and common types of substance use (alcohol, cannabis, nicotine) and early adversities.

Results: Neither childhood mental health symptoms nor substance use variables were associated with DNAm aging cross-sectionally. In contrast, the following mental health symptoms and substance variables were associated with accelerated DNAm aging from adolescence to adulthood: depressive symptoms (b = 0.314, SE = 0.127, p = .014), internalizing symptoms (b = 0.108, SE = 0.049, p = .029), weekly cannabis use (b =1.665, SE = 0.591, p = .005), and years of weekly cannabis use (b = 0.718, SE = 0.283, p = .012). In models testing all individual variables simultaneously, the combined effect of the variables was equivalent to a potential difference of 3.17 to 3.76 years in DNAm aging. A final model tested a variable assessing cumulative exposure to mental health symptoms, substance use, and early adversities. This cumulative variable was strongly associated with accelerated aging (b = 0.126, SE = 0.044, p = .005).

Conclusion: Mental health symptoms and substance use accelerated DNAm aging into adulthood in a manner consistent with a shared risk mechanism.

Plain Language Summary: Using data from 381 participants in the Great Smoky Mountains Study, the authors examined whether childhood mental health symptoms, substance use, and early adversity accelerate biological aging, as measured by DNA methylation age, from adolescence to adulthood. Depressive symptoms and cannabis use were found to significantly accelerate biological aging. Models that tested the combined effect of mental health symptoms, substance use, and early adversity demonstrated that there was a shared effect across these types of childhood problems on accelerated aging.