Kynurenine Pathway Dynamics in Depression and Mood Disorders
Summary
The kynurenine pathway is the principal route of tryptophan catabolism, generating metabolites that exert divergent effects on neural function and immune regulation. In depression and related mood disorders, chronic low-grade inflammation activates indoleamine 2,3-dioxygenase, shifting tryptophan degradation from serotonin synthesis towards kynurenine and its downstream products. An imbalance between neuroprotective metabolites such as kynurenic acid and neurotoxic species such as quinolinic acid contributes to glutamatergic dysregulation, impaired neurogenesis and synaptic plasticity. Sex differences, genetic polymorphisms and environmental factors further modulate pathway enzyme expression and metabolite ratios, influencing symptom severity, suicidal risk and treatment response. Peripheral kynurenine metabolites correlate with central measures of brain structure, notably hippocampal and amygdalar volumes, and with metabolic disturbances such as elevated body mass index. Therapeutic strategies aimed at restoring pathway balance—through enzyme inhibitors, receptor antagonists or adjunctive anti-inflammatory agents—hold promise for personalised interventions in mood disorders.
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Kynurenine Pathway Dynamics in Depression and Mood Disorders publication trend
The graph below shows the total number of articles in kynurenine pathway dynamics in depression and mood disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Kynurenine pathway (KP): The enzymatic cascade converting tryptophan into neuroactive metabolites such as kynurenic acid and quinolinic acid.
Indoleamine 2,3-dioxygenase (IDO): The rate-limiting enzyme that initiates tryptophan degradation along the kynurenine pathway under inflammatory conditions.
Kynurenic acid (KYNA): A neuroprotective metabolite that antagonises NMDA and α7-nicotinic receptors.
Quinolinic acid (QUIN): A neurotoxic metabolite and NMDA receptor agonist implicated in excitotoxicity.
Kynurenine 3-monooxygenase (KMO): An enzyme favouring the conversion of kynurenine to 3-hydroxykynurenine, promoting neurotoxic branch activity.
References
- Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression. Neuropsychopharmacology (2023).
- 1-Methyltryptophan treatment ameliorates high-fat diet-induced depression in mice through reversing changes in perineuronal nets. Translational Psychiatry (2024).
- Tryptophan Metabolism in Depression: A Narrative Review with a Focus on Serotonin and Kynurenine Pathways. International Journal of Molecular Sciences (2022).
- Peripheral and central kynurenine pathway abnormalities in major depression. Brain Behavior and Immunity (2022).
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