Inflammation-Associated Depression: From Serotonin to Kynurenine

By Robert Dantzer, Jason C. O'Connor, M. Lawson, Keith W. Kelley. Psychoneuroendocrinology, 2010

701 citations recorded by the source corpus.

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.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/da15b6e1b13cef6c65cb8211f1d5d6dbb4d20049

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In Behavioral Neuroscience

In Biological Psychiatry

Citations in the corpus

Inflammation: depression fans the flames and feasts on the heat. (2015, background): “Thiswell-establishedpathwaypromotes depression by simultaneously slowing serotonin production and enhancing levels of kynurenine, a tryptophan metabolite (22).”
Depression as a microglial disease. (2015, background): “, LPS, CpG, HIV Tat protein, and Bacillus Calmette–Guérin (BCG)] [21,125,126]), as well as by psychological stress and glucocorticoids [127] (Figure 2).”
Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications (2013, background): “Although alterations in 5-HT metabolism may not be the primary mediator of many behavioral symptoms resulting from cytokine-induced IDO activity (Dantzer et al., 2011, Maes et al., 2011), the 5-HT transporter (5-HTT) may serve as a biological substrate by which cytokines can affect 5-HT…”