Kynurenine pathway metabolites as biomarkers in major depressive disorder
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Abstract
The kynurenine pathway (KP) is the main route of tryptophan (TRP) degradation and an important axis of neuroimmune communication. This narrative review summarises clinical and preclinical evidence supporting KP metabolites as candidate biomarkers in major depressive disorder (MDD), with emphasis on KP imbalance and NAD⁺ homeostasis. Inflammation-driven activation of indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO), and kynurenine-3-monooxygenase (KMO) can divert flux toward the neurotoxic branch, increasing quinolinic acid (QA) and 3-hydroxykynurenine (3-HK) and reducing kynurenic acid (KYNA) formation. This pattern has been linked to higher symptom burden, phenotype-specific signals (including painful symptoms and suicidality), and impaired neuronal energetics [1, 2, 3]. QA-related excitotoxicity and oxidative stress may converge with NAD⁺ depletion and increased NAD⁺ consumption under cellular stress, amplifying metabolic vulnerability [3, 4]. We propose that KP dysregulation and NAD⁺ deficiency constitute a clinically relevant metabolic–energetic axis in MDD and that biomarker-stratified modulation of KP enzymes and/or NAD⁺ support warrants further translational study [4].
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References
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