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