Cytokines sing the blues: inflammation and the pathogenesis of depression.
Journal: 2006/November - Trends in Immunology
ISSN: 1471-4906
Increasing amounts of data suggest that inflammatory responses have an important role in the pathophysiology of depression. Depressed patients have been found to have higher levels of proinflammatory cytokines, acute phase proteins, chemokines and cellular adhesion molecules. In addition, therapeutic administration of the cytokine interferon-alpha leads to depression in up to 50% of patients. Moreover, proinflammatory cytokines have been found to interact with many of the pathophysiological domains that characterize depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior. Stress, which can precipitate depression, can also promote inflammatory responses through effects on sympathetic and parasympathetic nervous system pathways. Finally, depression might be a behavioral byproduct of early adaptive advantages conferred by genes that promote inflammation. These findings suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.
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Trends Immunol 27(1): 24-31

Cytokines sing the blues: inflammation and the pathogenesis of depression

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle, Suite 4000, Atlanta, GA 30322, USA
Corresponding author: Miller, A.H. (ude.yrome@20llima).


Increasing amounts of data suggest that inflammatory responses have an important role in the pathophysiology of depression. Depressed patients have been found to have higher levels of proinflammatory cytokines, acute phase proteins, chemokines and cellular adhesion molecules. In addition, therapeutic administration of the cytokine interferon-α leads to depression in up to 50% of patients. Moreover, proinflammatory cytokines have been found to interact with many of the pathophysiological domains that characterize depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior. Stress, which can precipitate depression, can also promote inflammatory responses through effects on sympathetic and parasympathetic nervous system pathways. Finally, depression might be a behavioral byproduct of early adaptive advantages conferred by genes that promote inflammation. These findings suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.


So much is lost from the lives of people who suffer with major depression that it was perhaps natural for initial discoveries regarding mood disorders and immunity to focus on yet another loss – in this case, diminished functioning of the humoral and cellular arms of the acquired immune response [1]. Nevertheless, data amassed over the past 15 years have led to a dramatic paradigm shift in which the early focus on immunosuppression has been subsumed within, and supplanted by, an increasing recognition that depressive disorders might be best characterized as conditions of immune activation, especially hyperactivity of innate immune inflammatory responses. This profound change in our view of depression and immunity has not occurred in isolation but rather is part of a larger scientific movement built around an increasing appreciation that inflammatory processes are central to the pathogenesis of several modern maladies, including cardiovascular disease, diabetes and cancer [24]. Indeed, much of the recent work linking depression with inflammation has been prompted by the search for potential shared etiological mechanisms that might explain the striking co-morbidity between these medical illnesses and major depression [5].

Evolutionary imperatives for the depression–inflammation link


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