The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis

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Reduced mental health (MH) is prevalent in rheumatoid arthritis (RA). Although longitudinal studies are limited, there is evidence that depression is associated with worse disease outcomes. We evaluated reciprocal relationships between MH, RA severity, and genetic risks for depression for 2 years in a well-characterized cohort of RA patients.


We evaluated 520 early RA patients previously enrolled to two clinical trials. MH was measured using the short form-36 MH domain and mental component summary scores (MCS). MCS/MH associations over 2 years with disease activity (disease activity score on a 28-joint count), disability (health assessment questionnaire), pain visual analog scale scores, and a weighted genetic risk score for depression were tested using linear mixed-effects and regression models.


Poorer MH was associated with worse RA outcomes. Lower MCS scores (indicating worse MH) were seen in patients with a greater genetic risk for depression (weighted genetic risk score: coefficient = −1.21, p = .013). Lower baseline MCS was associated with lower 2-year improvements in disease activity score on a 28-joint count (coefficient = −0.02, p < .001), pain (coefficient = −0.33, p < .001), and health assessment questionnaire (coefficient = −0.01, p = .006). Baseline MCS was associated with changes in the swollen joint count (coefficient = −0.09, p < .001) and patient global assessment (coefficient = −0.28, p < .001) but not the tender joint count (p = .983) and erythrocyte sedimentation rate (p = .973). Only baseline pain visual analog scale (coefficient = −0.07, p = .002) was associated with 2-year changes in MCS.


Reduced baseline MH was associated with lower improvements in disease activity, disability, and pain for 2 years, supporting current national guidelines recommending screening for depression in RA. Pain had a bidirectional relationship with MH. Depression genetic risk had a significant association with MH.

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