To investigate the association of depression with 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 the NHSII (1993-2015). Depression was defined according to the following composite definition: diagnosis by clinician, regular antidepressant use, or a 5-question Mental Health Inventory score of <60 using time-updated questionnaires during follow-up. Incident RA cases met research criteria by medical record review. Information on covariates, including smoking, diet, and body mass index, was obtained using questionnaires. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RA risk (overall and by serologic phenotype) according to depression status and 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 prior to diagnosis explained any associations.
Among 195,358 women, we identified 858 cases of incident RA (65% seropositive) over 3,087,556 person-years (median 17.9 years per participant). Compared to women without depression, those with depression had multivariable HRs as follows: 1.28 (95% CI 1.10-1.48) for all RA; 1.12 (95% CI 0.93-1.35) for seropositive RA; and 1.63 (95% CI 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 this finding was not explained by measured lifestyle factors prior to clinical presentation.