The potential impact of sickness-motivated behavior on the expression of neuropsychiatric disturbances in systemic lupus erythematosus

Summary Activation of the peripheral immune system is often accompanied by changes in cognition, ingestive behavior, sleep pattern, and sexual drive; collectively referred to as sickness behavior. Mounting evidence suggests that sickness behavior may be a purposeful attempt on the part of an organism to conserve energy and thereby facilitate recuperation. Illnesses characterized by chronic, uncontrolled immune reactivity such as systemic lupus erythematosus are also frequently associated with impaired emotionality and cognition; which, unlike sickness behavior, are conventionally thought to emanate from fixed structural lesions of the brain. Clinical observations, however, indicate that the neuropsychiatric disturbances in lupus may wax and wane in intensity and suggest the hypothesis that sickness-motivated behavior may significantly influence the neuropsychiatric manifestations of systemic lupus erythematosus and, perhaps, those of other autoimmune diseases associated with neuroinflammation. The hypothesis that patients with systemic lupus erythematosus undergo a reorganization of their motivational priorities, which influences cognitive performance and emotional output, may be examined using validated behavior paradigms in autoimmune MRL-MpJ-Tnfrsf6lpr (MRL- lpr/lpr ) mice that spontaneously develop a lupus-like illness accompanied by disturbances in cognition and emotionality. Confirming that sickness-motivated behavior contributes to the aberrations in cognition and emotionality exhibited by an experimental model of systemic lupus erythematosus might have important therapeutic and prognostic implications by invoking the possibility that similar motivational effects may be influencing cognitive and/or emotional output in patients with neuropsychiatric lupus.