Objective. An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA. Methods. In total, 218 RA outpatients completed self-administered questionnaires, using the Beck Depression Inventory II to measure depressive symptoms and a visual analog scale to quantify their perceived pain. Functional disability and CRP level were also measured. Results. Depression scores were mildly and positively correlated with the CRP level (r ؍ 0.46, P < 0.001). Both the depression score (standardized  ؍ 0.35, P < 0.001) and the CRP level (standardized  ؍ 0.35, P < 0.001) were significantly associated with pain, even after adjustment for clinical covariates in regression analysis. In logistic analysis, the combined effects on the risk of severe pain (pain score in the upper tertile) increased with depression scores and CRP levels linearly. Conclusion. Depression severity and inflammation were associated with each other and appeared to have independent effects on perceived pain. Therefore, a clinical approach that takes into account both the body and the mind could have benefits and could enable optimal pain control.
INTRODUCTIONRheumatoid arthritis (RA) is a chronic autoimmune disorder causing inflammation of the joints and surrounding tissues (1). Patients with RA experience pain, stiffness, swelling, and deterioration of joints. Severe chronic pain accompanied by progressive joint destruction, disability, and disfigurement is known to increase the risk of experiencing emotional disturbances (2). Indeed, depression is common among patients with RA (3,4); these patients are twice as likely to be depressed as people in the general population (5).The association between systemic inflammation and depression has recently attracted attention (6 -8). Depression could promote inflammation by fostering poor health practices, dysregulation of hormonal systems, and susceptibility to atherogenic infections (9,10). Alternatively, it has been suggested that systemic inflammation might induce depressive symptoms by activating the immune-brain pathway (11,12). Various inflammation markers have been reported to have positive associations with depression. C-reactive protein (CRP) is a nonspecific acute-phase protein synthesized in the liver in response to stimulation from interleukin-6 (IL-6) and IL-1. According to a recent review (8), CRP and its precursors IL-6 and IL-1 are the most intensively examined inflammation markers in relation to depression, and a positive association has been confirmed consistently in community and clinical samples. Associations between depression and leukocytosis, increased CD4:CD8 ratios, reduced proliferative response to mitogen, and reduced natural killer cell cytotoxity were also suggested in an earlier meta-analysis (13,14).To date, the asso...
