Joint Effects of Adverse Childhood Experiences and Genetic Burden of Depression on Multiple Depressive Symptoms

Adverse childhood experiences (ACEs) and genetic burden of depression are key factors influencing depression, but their joint effects remain unclear. This study explores the joint effects on depressive symptoms and examines the mediating role of ACEs. This study was based on data from the prospective cohort Health and Retirement Study (HRS), in which 6204 adults of European ancestry aged 50 years and older were analysed. ACEs were measured using the Psychosocial and Lifestyle Questionnaire (PLQ), and genetic burden was assessed via polygenic risk scores (PRS). Depressive symptoms (total, cognitive-affective, somatic) were evaluated with the Centre for Epidemiological Studies Depression Scale (CES-D). Multivariate Cox regression models were used to assess independent and joint effects, and mediation analysis tested whether genetic burden increased depression risk through ACEs. ACEs were associated with higher risks of total (HR = 1.305, 95% CI: 1.174, 1.451), somatic (1.337, 1.206-1.482), and cognitive-affective (1.247, 1.114-1.395) depressive symptoms. Increased genetic burden was also associated with elevated risks of total (HR = 1.088, 95% CI: 1.033, 1.147) and somatic (1.089, 1.035-1.147) depressive symptoms. Compared to those with no ACEs and low genetic burden, individuals with ACEs and high genetic burden had significantly higher risks of depressive symptoms (total: 60%, somatic: 63%, cognitive-affective: 43%). ACEs mediated the link between genetic burden and somatic symptoms. Both ACEs and genetic burden of depression are associated with an increased risk of depressive symptoms, and their joint effects significantly increase the risk of all types of depressive symptoms. Furthermore, genetic burden also indirectly elevates the risk of somatic depressive symptoms by influencing ACEs.