Depression and immunity: inflammation and depressive symptoms in multiple sclerosis.
There is strong evidence that depression involves alterations in multiple aspects of immunity that may contribute to the development or exacerbation of a number of medical disorders and also may play a role in the pathophysiology of depressive symptoms. Accordingly, aggressive management of depressive disorders in medically ill populations or individuals at risk for disease may improve disease outcome or prevent disease development. On the other hand, in light of data suggesting that immune processes may interact with the pathophysiologic pathways known to contribute to depression, novel approaches to the treatment of depression may target relevant aspects of the immune response. Taken together, the data provide compelling evidence that a psychoimmunologic frame of reference may have profound implications regarding the consequences and treatment of depression. In addition, this approach may be used to investigate the possibility that peripheral and central production of cytokines may account for neuropsychiatric symptoms in inflammatory diseases. This article summarizes evidence for a cytokine-mediated pathogenesis of depression and fatigue in MS. The effects of central inflammatory processes may account for some of the behavioral symptoms seen in patients who have MS that cannot be explained by psychosocial factors or CNS damage. This immune-mediated hypothesis is supported by indirect evidence from experimental and clinical studies of the effect of cytokines on behavior, which have found that both peripheral and central cytokines may cause depressive symptoms. Emerging clinical data from patients who have MS support an association of central inflammation (as measured by MRI) and inflammatory markers with depressive symptoms and fatigue. Based on the literature reviewed in this article, subtypes of MS fatigue and depression may exist that are caused by different pathogenetic mechanisms, including inflammation and CNS damage as well as psychosocial factors or predisposition. The existence of these subtypes could have important clinical implications. For example, an inflammatory depression may require different therapeutic approaches than a reactive depression in MS. Future research should aim to characterize these subtypes better with the goal of optimizing treatment.
Gold
Stefan M
SM
Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience, 300 Medical Plaza, Suite 3109, Los Angeles, CA 90095, USA. sgold@mednet.ucla.edu
Irwin
Michael R
MR
D000818:Animals; D001921:Brain / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000276:immunology* / Q000523:psychology; D003865:Major Depressive Disorder / Q000276:immunology* / Q000523:psychology; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000276:immunology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000523:psychology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011598:Psychoneuroimmunology; D012307:Risk Factors; D012803:Sick Role
D016207:Cytokines