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Current Immunology Reviews (Discontinued)


ISSN (Print): 1573-3955
ISSN (Online): 1875-631X

The Concept of Depression as a Dysfunction of the Immune System

Author(s): Brian E. Leonard

Volume 6, Issue 3, 2010

Page: [205 - 212] Pages: 8

DOI: 10.2174/157339510791823835

Price: $65


Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis and the immune system, acts as a trigger for anxiety and depression. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids, as occurs in chronically stressful situations and in depression, contribute to the behavioural changes associated with depression. A defect in serotonergic function is associated with hypercortisolaemia and the increase in proinflammatory cytokines that accompany depression. Glucocorticoids and proinflammatory cytokines enhance the conversion of tryptophan to kynurenine. In addition to the resulting decrease in the synthesis of brain serotonin, this leads to the formation of neurotoxins such as the glutamate agonist quinolinic acid and contributes to the increase in apoptosis of astrocytes, oligodendroglia and neurons. The importance of the inflammation hypothesis of depression lies in raising the possibility which psychotropic drugs that have a central anti-inflammatory action might provide a new generation of antidepressants.

Keywords: Proinflammatory cytokines, inflammation, glucocorticoids, serotonin, tryptophan-kynurenine pathway

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