Background/Purpose: The underlying risk factors for the development of Rheumatoid Arthritis (RA) remain poorly understood; however, prospective studies have demonstrated that individuals with elevated Tumor Necrosis Factor alpha (TNFα), a pro-inflammatory cytokine, are at increased risk of subsequently developing RA. It remains unknown whether elevated TNFα by means of a different disease process can subsequently increase the risk of developing RA. Recently, major depressive disorder (MDD) has been identified to have a direct effect on cytokines, including increased serum concentrations of TNFα relative to healthy controls independent of underlying inflammatory disease. Based on this, our hypothesis is that exposure to MDD may increase the risk of subsequently developing RA. In this study using a large population-based cohort, we assessed if patients with MDD were at increased risk of subsequently developing RA compared to the general population without MDD.

Methods: A retrospective cohort study was conducted using The Health Improvement Network (THIN) Database between the years 1986-2012 for up to 26 years of follow-up. The MDD cohort comprised patients with a diagnostic (Read) code for MDD and the remainder of patients formed the referent cohort. Both cohorts were followed until patients developed RA or were censored. Cox proportional hazards models were used to determine the risk of developing RA among patients with MDD, as reported using Hazard Ratios (HRs) and 95% confidence intervals (CIs) (α=0.05). A backward elimination procedure was used to determine the presence of effect modification (using a Wald test) or confounding by age or sex.

Results: A cohort of 403,932 patients with MDD and a referent cohort of 5,339,399 patients without MDD were identified in THIN. A total of 2,192 (0.54%) patients with MDD developed RA, and 24,021 (0.45%) patients without MDD developed RA over this period. Cox proportional hazards models identified a confounding effect by sex and a significant interaction by age (p<0.0001), whereby younger patients with MDD (age<40) had a 42% increased risk of developing RA (sex-adjusted HR=1.42, 95%CI: 1.31 – 1.53). In older patients (age>40), the risk of developing RA among those with MDD was lower but demonstrated a 14% increased risk (sex-adjusted HR=1.14, 95%CI: 1.08-1.21).

Conclusion: MDD was found to be a risk factor for the development of RA. This risk was highest among younger patients with MDD, and the risk was only somewhat increased among older patients with MDD. These results provide support the hypothesis that MDD may be associated with the development of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/depression-as-a-risk-factor-for-the-development-of-rheumatoid-arthritis-a-population-based-cohort-study/