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

OBJECTIVE:This study tests whether childhood mental health symptoms, substance use and early adversity accelerate the rate of DNA methylation (DNAm) aging from adolescence to adulthood. METHOD:381 participants had DNAm assayed from blood in both adolescence (average age 13.9; SD 1.6 years) and adulthood (average age 25.9; SD 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 (ADHD, ODD, CD, anxiety, and depression) as well as 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 [SE] = 0.314 [0.127], P = .014), internalizing symptoms (b [SE] = 0.108 [0.049], p = .029), weekly cannabis use (b [SE] =1.665 [0.591], P = .005), and years of weekly cannabis use (b [SE] = 0.718 [0.283], P = .012). In models testing all individual variables simultaneously, the combined effect of the variables was equivalent to a potential 3.17 to 3.76 years difference 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 [SE] =0.126 [0.044], P = .005). CONCLUSION:Mental health symptoms and substance use accelerated DNA methylation aging into adulthood in a manner consistent with a shared risk mechanism.