Skip to Main Content


It is easy to think about rheumatologic illnesses, including chronic inflammatory and arthritic conditions such as rheumatoid arthritis (RA), as disorders that primarily affect the musculoskeletal and immune systems. But these rheumatologic disorders have prominent neuropsychiatric symptoms and many other confounding and complicating factors. Pain, systemic inflammation, disability, fatigue, sleep disruption, and treatment effects—all of these accompany rheumatologic conditions, and are associated with depression in and of themselves.

Although some rheumatologic illnesses—most notably systemic lupus erythematosus—directly cause neuropsychiatric symptoms, the depression occurring in most of these patients is multifactorial. This chapter reviews the diagnosis and treatment of depression when it occurs in the context of a rheumatologic disease. It includes an initial discussion of the role of two salient factors common to rheumatologic disease in general—systemic inflammation and corticosteroid treatment—and then turns to the specific diseases whose association with depression has been studied: systemic lupus, RA, scleroderma, and fibromyalgia.


The relationship of depression to inflammatory processes has long been a subject of investigation.1 Significant associations were discovered between inflammation and depression, including epidemiologic observations (the high female to male ratio, and lower rates of depression in cultures with diets rich in fish) and biological associations (e.g., between symptoms of depression and pro-inflammatory cytokines). Although there is strong evidence of a link between depression and inflammation, the precise mechanisms remain elusive.

Depression is substantially more prevalent in patients with rheumatologic illnesses than in the general population,2 and depression is highly correlated with disease-related morbidity within this population. Compared to other major medical comorbidities, patients with rheumatologic illness exhibit the strongest correlation between depression and lower quality of life measurements.3 Depression also appears to predict work disability more strongly in this population than among patients without a rheumatic illness.4

The link between depression and rheumatologic illnesses likely includes both psychological and biological components. Restricted independence, higher medical burden, and patients' concerns about appearance (e.g., skin lesions or musculoskeletal deformities) have all been associated with depression in these patients.5,6

What is known about the biological link between depression and systemic inflammation remains limited, but some associations have been demonstrated in research studies (Chapters 1 and 2). Healthy test subjects given an endotoxin (which promotes systemic inflammation as manifested by a rise in body temperature and in pro-inflammatory cytokines) (Table 10-1) develop depressed mood, anxiety, and memory impairment.7 Patients with existing major depression have higher concentrations of TNFa and IL-6 even without stimulation by an endotoxin.8

TABLE 10-1Proinflammatory Cytokines Studied in Depression

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.