Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies
Open accessAbstract
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.
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Statins may decrease the activity of the enzyme indoleamine 2,3-dioxygenase, which is induced by IFN-gamma, leading to the cleavage of tryptophan, a precursor of serotonin and melatonin, as well as the production of neurotoxic tryptophan catabolites.
“Furthermore, statins may decrease the activity of the enzyme indoleamine 2,3-dioxygenase [175], which is induced by IFN-γ, leading to the cleavage of the essential amino acid tryptophan, a precursor of serotonin and melatonin, as well as the production of neurotoxic tryptophan catabolites [176].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [176]
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References 143 · Cited by 221
Research works printed but not linked: 2
- Delgado PL Depression: the case for a monoamine deficiency J Clin Psychiatry 2006 61 7 11 10775018
- Laugeray A Launay JM Callebert J Surget A Belzung C Barone PR Evidence for a key role of the peripheral kynurenine pathway in the modulation of anxiety- and depression-like behaviours in mice: focus on individual differences Pharmacol Biochem Behav 2011 98 161 8 21167857
- Authors
- Réus, G. Z., Jansen, K., Titus, S., Carvalho, A. F., Gabbay, V., & Quevedo, J.
- Affiliations
- Universidade do Extremo Sul Catarinense (BR)
- Universidade Católica de Pelotas (BR)
- The University of Texas Health Science Center at Houston (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Réus, Gislaine Z.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 68
- Pages
- 316-328
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC4955923
- OpenAlex
- W1484783577
- Cited by
- 221
- References
- 143
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 26 · 2023: 13 · 2022: 30 · 2021: 25 · 2020: 21 · 2019: 25 · 2018: 21 · 2017: 14 · 2016: 16 · 2015: 5
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH095807, R01MH101479)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- kynurenine pathway, major depressive disorder, treatment-resistant depression, tryptophan degradation, inflammation, antidepressant targets, monoamine hypothesis, inflammatory mediators, newer antidepressants
- MeSH terms
- Animals, Major Depressive Disorder, Humans, Kynurenine, Metabolic Networks and Pathways
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