ReviewWorld journal of psychiatry2023
Kynurenine pathway of tryptophan metabolism in pathophysiology and therapy of major depressive disorder.
Review in World journal of psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Design, Synthesis, and Biological Evaluation of Novel Morpholine-Coumarin Derivatives for Inflammation-Associated Depression.Biomolecules · 2026Article
- Nutritional Interventions for Perimenopausal Anxiety and Depression Targeting Tryptophan and GABA Pathways: A Narrative Review.Nutrients · 2026Review
- Systemic inflammation and mental health: A J-shaped dose-response pattern in depression based on NHANES 2005 to 2018.Medicine · 2026Article
- Review
- Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms.Translational psychiatry · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Review
- NADPH alleviates LPS-induced neuropathology and depression-like behaviors by suppressing microglial inflammatory response.Translational psychiatry · 2025Article
- Review
- Gut-brain-immune axis implications for mental health and disease.Molecular and cellular biochemistry · 2025Review
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Unlocking the potential of the 3-hydroxykynurenine/kynurenic acid ratio: a promising biomarker in adolescent major depressive disorder.European archives of psychiatry and clinical neuroscience · 2025Article
- Genome-wide interaction association analysis identifies interactive effects of childhood maltreatment and kynurenine pathway on depression.Nature communications · 2025Article
- IDO and TDO inhibitors in cancer immunotherapy: mechanisms, clinical development, and future directions.Frontiers in pharmacology · 2025Review
- Comparing plasma levels and ratios of tryptophan, serotonin, kynurenine and quinolinic acid between patients with bipolar disorder and healthy controls: impact of depressive episode or post-traumatic stress disorder symptoms.Frontiers in psychiatry · 2025Article
- Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder.PloS one · 2025Article
- Depression, stress, and tryptophan metabolism through the kynurenine pathway: treatment strategies from the perspective of Chinese herbal medicine.Metabolic brain disease · 2024Review
- The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Research fronts and researchers ofWorld journal of psychiatry · 2024Article
- Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavior Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotonin deficiency in major depressive disorder (MDD) has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan (Trp)-degrading enzyme, liver Trp 2,3-dioxygenase (TDO), by cortisol, leading to decreased Trp availability to the brain for serotonin synthesis. Subsequently, the serotonin deficiency was proposed to involve induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase (IDO) by proinflammatory cytokines, with inflammation being the underlying cause. Recent evidence, however, challenges this latter concept, as not all MDD patients are immune-activated and, when present, inflammation is mild and/or transient. A wide range of antidepressant drugs inhibit the activity of liver TDO and bind specifically to the enzyme, but not to IDO. IDO induction is not a major event in MDD, but, when it occurs, its metabolic consequences may be masked and overridden by upregulation of kynurenine monooxygenase (KMO), the gateway to production of modulators of immune and neuronal functions. KMO appears to be activated in MDD by certain proinflammatory cytokines and antidepressants with anti-inflammatory properties may block this activation. We demonstrate the ability of the antidepressant ketamine to dock (bind) to KMO. The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation. Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.
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