title: Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies.
abstract: Treatment-resistant depression affects up to 20% of individuals suffering from major depressive disorder (MDD). The medications currently available to treat depression, including serotonin re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), fail to produce adequate remission of depressive symptoms for a large number of patients. The monoamine hypothesis upon which these medications are predicated should be expanded and revised as research elucidates alternative mechanisms of depression and effective methods to treat the underlying pathologic consequences. Research into the role of tryptophan degradation and the kynurenine pathway in the setting of inflammation has brought new insight into potential etiologies of MDD. Further investigation into the connection between inflammatory mediators, tryptophan degradation, and MDD can provide many targets for novel antidepressant therapies. Thus, this review will highlight the role of the kynurenine pathway in the pathophysiology of depression, as well as a novel therapeutic target to classic and new modulators to treat depression based on findings from preclinical and clinical studies.
authors.affiliation: Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil. Electronic address: gislaine.z.reus@uth.tmc.edu.
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.affiliation: Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA; Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, Brazil.
authors.forename: Karen
authors.initials: K
authors.lastname: Jansen
authors.affiliation: Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Titus
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Vilma
authors.initials: V
authors.lastname: Gabbay
authors.affiliation: Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*
chemical_list: D007737:Kynurenine
keywords: Depression; Indoleamine 2,3–dioxygenase; Inflammation; Kynurenine pathway; Tryptophan