Dimensions of childhood adversity differentially affect biological aging in major depression

Adverse childhood experiences have been consistently linked with physical and mental health disorders in adulthood that may be mediated, in part, via the effects of such exposures on biological aging. Using recently developed "epigenetic clocks", which provide an estimate of biological age, several studies have demonstrated a link between the cumulative exposure to childhood adversities and accelerated epigenetic aging. However, not all childhood adversities are equivalent and less is known about how distinct dimensions of childhood adversity relate to epigenetic aging metrics. Using two measures of childhood adversity exposure, we assess how the dimensions of Maltreatment and Household Dysfunction relate to epigenetic aging using two "second-generation" clocks, GrimAge and PhenoAge, in a cohort of unmedicated somatically healthy adults with moderate to severe major depression (n = 82). Our results demonstrate that the dimension of Maltreatment is associated with epigenetic age acceleration (EAA) using the PhenoAge but not the GrimAge clock. This association was observed using both the Childhood Trauma questionnaire (CTQ; β = 0.272, p = 0.013) and the Adverse Childhood Experiences (ACEs) questionnaire (β = 0.307, p = 0.005) and remained significant when adjusting for exposure to the dimension of Household Dysfunction (β = 0.322, p = 0.009). In contrast, the dimension of Household Dysfunction is associated with epigenetic age deceleration (β = -0.194, p = 0.083) which achieved significance after adjusting for exposure to the dimension of Maltreatment (β = -0.304, p = 0.022). This study is the first to investigate these effects among individuals with Major Depressive Disorder and suggests that these dimensions of adversity may be associated with disease via distinct biological mechanisms.