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Robert Dantzer"Inflammation and depression"

Abstract :


In the field of depression, inflammation-associated depression stands up as an exception since its causal factors are obvious and it is easy to mimic in an animal model.
In addition, quasi-experimental studies can be carried out in patients who are treated chronically with recombinant cytokines for a medical condition since these patients can be studied longitudinally before, during and after stimulation of the immune system. These clinical studies have revealed that depression is a late phenomenon that develops over a background of early appearing sickness.
Incorporation of this feature in animal models of inflammation-associated depression has allowed the demonstration that alterations of brain serotoninergic neurotransmission do not play a major role in the pathogenesis. This is in contrast to the activation of the tryptotphan degrading enzyme indoleamine 2,3-dioxygenase that generates potentially neurotoxic kynurenine metabolites such as 3-hydroxy kynurenine and quinolinic acid. Although the relative importance of peripherally versus centrally produced kynurenine and the cellular source of production of this compound remain to be determined, these findings provide new targets for the treatment of inflammation-associated depression that could be extended to other psychiatric conditions mediated by activation of neuroimmune mechanisms.

Selected publications

Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, Spivey JR, Saito K, Miller AH. (2010). CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry.
O'Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW, Dantzer R. (2009). Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci. 29(13): 4200-4209.
O'Connor JC, Lawson MA, André C, Moreau M, Lestage J, Castanon N, Kelley KW, Dantzer R (2009). Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry. 14(5):

Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 9(1): 46-56. Review.

Guillaume Ferreira du groupe Psynugen. INRA 1286 - CNRS 5226