The Association Between Autoimmune Rheumatic Diseases and Depression: A Two-Sample Bidirectional Mendelian Randomization.

Background: Although prior observational studies have indicated an association between depression and autoimmune rheumatic diseases (ARDs), the underlying causal relationship remains unclear.

Methods: A two-sample bidirectional Mendelian randomization (MR) study was conducted to explore the causal link between depression and ARDs. Genetic data for both depression and ARDs were obtained from publicly available genetic datasets. Instrumental variables were chosen as independent single-nucleotide polymorphisms (SNPs) linked to each condition. The main analysis employed the random-effects inverse-variance weighted (IVW) method, supplemented by MR-Egger regression and the weighted median approach to strengthen the robustness of the findings.

Results: The IVW analysis identified a significant link between depression and a heightened risk of several ARDs: Sjögren's syndrome (OR = 1.546, p < .001), fibromyalgia syndrome (OR = 5.000, p < .001), psoriasis (OR = 1.185, p = .009), and psoriatic arthritis (OR = 1.333, p = .01). No association was found for rheumatoid arthritis, systemic lupus erythematosus, rheumatic polymyalgia, systemic sclerosis, gout, polymyositis, or Behçet's disease. These results were consistent across the MR-Egger and weighted median analyses. The reverse MR analysis found no significant causal effect of any ARD on depression risk.

Conclusions: In conclusion, this MR study suggests that individuals with depression are at high risk for certain ARDs, highlighting the importance of timely screening, early detection, and intervention. Additional studies are required to elucidate the exact connection and mechanisms linking depression with particular ARDs.