Mental health across the lifecourse as predictors of epigenetic aging from a longitudinal birth cohort in the United States

Poor mental health has been linked with an increased risk of accelerated aging. This study examines associations between indicators of poor mental health across the life course and markers of epigenetic aging among 274 participants from the Child Health and Development Studies (CHDS) Disparities (DISPAR) Study. The sample included those with complete data on indicators of mental health in childhood (age 9-11) (sadness/isolated and anxious/fearful) and adulthood (age 50) (psychological distress and depressive symptoms). Epigenetic age acceleration (in blood) was estimated using two generations of epigenetic clocks and one DNA methylation biomarker in adulthood (DunedinPACE). We used path analysis to evaluate both direct and indirect effects of child mental health and epigenetic aging with mediation through adult mental health. Among menopausal females, higher psychological distress in adulthood was associated with greater epigenetic aging through PhenoAge Acceleration [Beta (95 % CI)] [0.27 (0.001,0.53)]. Higher depressive symptoms was associated with lower epigenetic aging through GrimAge Acceleration among menopausal females [-0.30 (-0.51,-0.09)] and through PhenoAge [-0.35 (-0.61,-0.10)]. Higher sadness/isolated scores in childhood were associated with higher epigenetic aging through PhenoAge Acceleration among males [0.20 (0.03,0.38)]. No indirect effects were found. Overall, we found sex and time-period differences in how mental health measures are associated with epigenetic age.