Rheumatoid arthritis and depression: an inflammatory perspective

The coexistence of immune-mediated inflammatory diseases with depression has long been recognised. Data that illustrate the intimate associations between peripheral and brain immune responses raise the possibility of shared pathophysiological mechanisms. These associations include the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotrophic factors, and measures of synaptic plasticity. The evidence supporting this association is accumulating and includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements in physical disease scores. In this Review, we assess this evidence in relation to rheumatoid arthritis and depression, with a focus on innate immune and molecular responses to inflammation, and discuss the challenges of assessing causation in this population, acknowledging the difficulty of assessing the confounding and contributory effects of pain and fatigue. We also discuss how future clinical and preclinical research might improve diagnosis of depression in people with rheumatoid arthritis and shed light on mechanisms that could be substrates for therapeutic interventions.