Background Depression is common among patients with rheumatoid arthritis (RA) and is associated with adverse clinical outcomes. Vitamin D deficiency (VDD) is also prevalent in patients with RA and has been linked to depressive symptoms in cross-sectional studies; however, longitudinal data on its association with incident depression are limited. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (2010–2024). Adults with RA and serum 25-hydroxyvitamin D levels were identified and classified as having VDD (20 ng/mL) or sufficient vitamin D levels (≥30 ng/mL). After 1:1 propensity score matching for demographics, comorbidities, medications, and laboratory variables, 18,339 patients were included in each group. A 180-day landmark period was applied to strengthen the temporal ordering. The primary outcome was the incidence of depression. The secondary outcomes included antidepressant use, suicide-related events, and all-cause mortality. Negative and positive control outcomes were also examined. Results Compared with sufficient vitamin D levels, VDD was associated with a higher risk of incident depression (HR 1.64, 95% CI 1.50–1.78; p 0.001). Similar patterns were observed for antidepressant use (HR 1.46, p 0.001), suicide-related events (HR 1.62, p = 0.045), and all-cause mortality (HR 1.40, p 0.001). The negative control outcome was not significantly associated with VDD, whereas the positive control outcome showed the expected association. The findings were generally consistent across sensitivity, subgroup (sex-based), and exposure-gradient analyses. Conclusion Among patients with RA, VDD was associated with a higher long-term risk of incident depression. These findings support a possible association between vitamin D status and depression risk in this population; however, a causal inference cannot be established from this observational study.
Lan et al. (Thu,) studied this question.