OBJECTIVES:Prior research on the relationship between early adversity and adult chronic disease has often relied on retrospective reports of a limited range of exposures and has not considered childhood psychological distress as a mediator. We investigate whether distress in childhood is one pathway by which early social disadvantage leads to greater cardiometabolic risk in middle adulthood.METHODS:Data are from the 1958 British Birth Cohort study (sample n = 6027). We created an early social disadvantage index based on 16 exposures related to family and socioeconomic hardship from birth to age 7. Childhood psychological distress was ascertained from internalizing and externalizing symptoms at ages 7, 11, and 16 years. Cardiometabolic risk was assessed with a Z-standardized score derived from 9 immune, cardiovascular, and metabolic biomarkers measured at age 45. We used linear regression models and formal tests of mediation to assess relationships between disadvantage, distress, and subsequent cardiometabolic risk.RESULTS:Higher social disadvantage predicted increased adult cardiometabolic risk (β = 0.05; 95% CI = 0.03-0.07). Mediation analyses revealed a significant direct (path c’; β = 0.03; 95% CI = 0.01-0.05) and indirect (path ab; β = 0.02; 95% CI = 0.01-0.02) effect of social disadvantage on cardiometabolic risk, adjusting for potential confounders. Child psychological distress accounted for 37% (95% CI = 34-46%) of the observed association.CONCLUSIONS:Results suggest childhood distress may be one factor on the pathway linking early disadvantage to higher risk of developing cardiometabolic diseases. Such results may point to the importance of blocking the translation of psychosocial to biological risk during a potentially sensitive developmental window.