We investigated the association of depression with the subsequent risk of rheumatoid arthritis (RA) by serologic phenotype. 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 four years to lower the possibility that depressive symptoms due to early RA symptoms before diagnosis explained any associations.
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).
Indicators of depression, specifically antidepressant use, were associated with subsequent increased risk for seronegative RA, and measured lifestyle factors did not explain this finding before clinical presentation.