Depression and subsequent risk for incident rheumatoid arthritis among women

OBJECTIVE We investigated the association of depression with subsequent risk of rheumatoid arthritis (RA) by serologic phenotype. METHODS We performed a cohort study using pooled data from the Nurses' Health Study (NHS, 1992-2014) and NHSII (1993-2015). Depression was defined using a composite definition: clinician diagnosis, regular antidepressant use, or Mental Health Inventory-5 score <60 by time-updated questionnaires during follow-up. Incident RA cases met research criteria by medical review. Covariates, including smoking, diet, and body mass index, were obtained by questionnaires. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for RA (overall and by serologic phenotype) according to depression status, adjusted for potential confounders. All analyses included a time separation between assessments of depression and the window for RA risk of at least 4 years to lower the possibility that depressive symptoms due to early RA symptoms prior to diagnosis explained any associations. RESULTS Among 195,358 women, we identified 858 incident RA cases (65% seropositive) over 3,087,556 person-years (median 17.9 years/participant). Compared to women without depression, those with depression had multivariable HRs (95%CIs) of: 1.28(1.10-1.48) for all RA; 1.12(0.93-1.35) for seropositive RA; and 1.63(1.27-2.09) for seronegative RA. When analyzing components of the composite depression exposure variable, regular antidepressant use was not associated with subsequent seropositive RA (HR 1.21, 95%CI 0.97-1.49) and was associated with seronegative RA (HR 1.75, 95%CI 1.32-2.32). CONCLUSION Indicators of depression, specifically antidepressant use, were associated with subsequent increased risk for seronegative RA, and this finding was not explained by measured lifestyle factors prior to clinical presentation.