Article

Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Biological psychiatry (Impact Factor: 10.26). 02/2009; 65(9):732-41. DOI: 10.1016/j.biopsych.2008.11.029
Source: PubMed

ABSTRACT

Recognition that inflammation may represent a common mechanism of disease has been extended to include neuropsychiatric disorders including major depression. Patients with major depression have been found to exhibit increased peripheral blood inflammatory biomarkers, including inflammatory cytokines, which have been shown to access the brain and interact with virtually every pathophysiologic domain known to be involved in depression, including neurotransmitter metabolism, neuroendocrine function, and neural plasticity. Indeed, activation of inflammatory pathways within the brain is believed to contribute to a confluence of decreased neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity and loss of glial elements, consistent with neuropathologic findings that characterize depressive disorders. Further instantiating the link between inflammation and depression are data demonstrating that psychosocial stress, a well-known precipitant of mood disorders, is capable of stimulating inflammatory signaling molecules, including nuclear factor kappa B, in part, through activation of sympathetic nervous system outflow pathways. Interestingly, depressed patients with increased inflammatory biomarkers have been found to be more likely to exhibit treatment resistance, and in several studies, antidepressant therapy has been associated with decreased inflammatory responses. Finally, preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication. Translational implications of these findings include the unique opportunity to identify relevant patient populations, apply immune-targeted therapies, and monitor therapeutic efficacy at the level of the immune system in addition to behavior.

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Article: Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

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    • "NF-κB, p38 MAPK, and signal transducer and activator of transcription 5 (STAT5) are major mediators of pro-inflammatory cytokines, which inhibit GR function (Pace et al., 2007). The relationship between pro-inflammatory cytokines and GR resistance was initially investigated in patients with inflammatory diseases (Pace and Miller, 2009). Glucocorticoid receptor signaling was inhibited by IL-1β in patients with inflammatory bowel syndrome who did not respond to glucocorticoid treatment. "
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