Childhood psychiatric symptoms may be associated with advanced biological aging. This study examined whether epigenetic age acceleration (EAA) associates with internalizing and externalizing symptoms that were prospectively collected across childhood in a longitudinal cohort study. At age 6 buccal epithelial cells from 148 children (69 girls) were collected to survey genome-wide DNA methylation. EAA was estimated using the Horvath clock. Internalizing symptoms at ages 2.5 and 4 years significantly predicted higher EAA at age 6, which in turn was significantly associated with internalizing symptoms at ages 6–۱۰ years. Similar trends for externalizing symptoms did not reach statistical significance. These findings indicate advanced biological aging in relation to child mental health and may help better identify those at risk for lasting impairments associated with internalizing disorders.

۱٫ Introduction

Common mental health disorders, such as anxiety and depression, result in chronic human suffering and come at a large economic cost (Whiteford et al., 2013). As psychiatric symptoms often have their origins early in life (Reef, Diamantopoulou, van Meurs, Verhulst, & van der Ende, 2009), early indicators of childhood psychiatric symptoms are of high importance. Recent studies show that depressive symptoms in childhood and adolescence may be associated with advanced physical aging, such as early pubertal and adrenarcheal timing (Copeland, Worthman, Shanahan, Costello, & Angold, 2019; Ellis et al., 2019; Lewis et al., 2018), possibly due to early life adversity (Gur et al., 2019). Here we examine whether an indicator of advanced biological aging based on genomic DNA methylation, i.e., epigenetic age acceleration (EAA), is associated with childhood psychiatric symptoms.