Neurochemical and behavioral responses to inflammatory immune stressors

Activation of the inflammatory immune system has been associated with the development of psychological disorders such as major depressive disorder (MDD). In this regard, the release of pro-inflammatory cytokines (signaling molecules of the immune system) provokes a constellation of neurochemical and behavioral alterations, reminiscent of the effects of traditional stressors, which if sustained could influence psychological functioning. In animal models, exogenously administered cytokines, as well as bacterial endotoxins and viral analogues, induce a variety of behavioral disturbances collectively known as sickness behavior. Although it is difficult to differentiate the general malaise of sickness engendered by cytokines from the depressogenic effects, clinical studies have revealed increased levels of circulating cytokines and acute phase proteins in patients diagnosed with MDD. Furthermore, the incidence of MDD is increased in patients suffering from chronic inflammatory conditions, and immunotherapy used to treat chronic illnesses such as Hepatitis C was related to high levels of depression that could be attenuated by antidepressant treatment. Together, these findings indicate that activation of the inflammatory immune system may favor the evolution of psychological disturbances.