Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Inflammation, Serotonin and Major Depression

Author(s): Mario Catena-Dell’Osso, Francesco Rotella, Adriana Dell’Osso, Andrea Fagiolini and Donatella Marazziti

Affiliation: Department of Clinical and Experimental Medicine, University of Pisavia Roma, 67 I-56100 Pisa, Italy.

Keywords: Cytokines, Indoleamine 2, 3 dioxygenase (IDO), inflammation, major depressive disorder (MDD), serotonin (5- HT), stress, tryptophan catabolites along the IDO pathway (TRYCATs).

Abstract:

The understanding of the neurobiological processes leading to major depressive disorder (MDD) is an active field of research in the scientific community. For years, the alteration of monoamine neurotransmission, in particular serotonin (5-HT), has been considered the most significant pathophysiological mechanism of the disorder. However, biological data supporting the postulated MDD-related monoamine alterations have been inconclusive, and the use of monoaminergic antidepressants has not yielded the expected results. In the last few years, it has been demonstrated that inflammatory pathways have a significant role in the pathophysiology of MDD. According to the cytokine hypothesis, the disorder would be due to a stress-related increased production of cytokines, including interleukins, tumor necrosis factor-α and interferon- α and γ. These, in turns, would cause the activation of the indoleamine 2,3 dioxygenase (IDO), with subsequent production of tryptophan (TRP) catabolites along the IDO pathway (TRYCATs) and decreased availability of TRP and 5-HT. Besides monoamines, other molecular mechanisms, as those within the inflammatory pathways, should be taken into account in the attempt to clarify the pathophysiology of MDD and to improve its treatment.

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Article Details

VOLUME: 14
ISSUE: 5
Page: [571 - 577]
Pages: 7
DOI: 10.2174/13894501113149990154