Accelerated aging mediates the association between rheumatoid arthritis and depression severity

BACKGROUND: This study aimed to investigate the associations among phenotypic age acceleration (PAA), the prevalence of rheumatoid arthritis (RA), and depression severity and to examine the potential mediating role of PAA in the RA-depression relationship. METHODS: A retrospective cohort analysis was conducted using data from adult participants in the National Health and Nutrition Examination Survey (2005-2010). Participants with RA were identified on the basis of self-report of RA in personal interviews. Depression was assessed via the Patient Health Questionnaire-9 (PHQ-9). PAA was calculated with 9 clinical biomarkers and chronological age, with a relatively high RAA value indicating the acceleration of aging. Survey-weighted logistic regression models were used to explore the relationship between the prevalence of RA and PAA and the correlation between PAA and depression. Mediation analysis was employed to quantify the indirect effect of RA on depression through PAA. RESULTS: A total of 9834 adults aged over 20 years were included. RA prevalence was positively associated with greater PAA (β = 1.60, 95 % confidence interval (CI): 0.86-2.35, P = 0.0002) and depression severity (β = 1.57, 95 % CI: 1.09-2.05, P < 0.0001). Additionally, PAA was correlated with depression severity (β = 0.04, 95 % CI: 0.02-0.06; P = 0.0001). Mediation analysis revealed that PAA significantly mediated the association between RA and depressive severity, explaining 2.26-5.57 % (all p < 0.001) of the total effect. CONCLUSIONS: Individuals with RA exhibited accelerated biological aging, as represented by increased PAA, which partially mediated the relationship between RA and depression severity in this population.