Kynurenine pathway in major depression: Evidence of impaired neuroprotection
Abstract
The neurodegeneration hypothesis proposed major depression as a consequence of the imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway. To test the hypothesis, plasma tryptophan and kynurenine pathway metabolites were studied in 58 patients with major depression and 189 normal controls. The mean tryptophan breakdown index was higher (p=0.036), and mean kynurenic acid concentration and mean neuroprotective ratios were lower, in depressed patients (p=0.003 and 0.003, respectively). In receiver operating characteristic analysis, the kynurenic acid concentrations and the neuroprotective ratio showed clear discrimination between depressed patients and controls with area under the curve 79% and 76.3% respectively. The neuroprotective ratio did not change after treatment in those with repeated episodes of depression but it increased significantly (p=0.044) in those with first episodes. The results suggested that the reduction in neuroprotective markers, which indicated an impaired neuroprotection, might play an important role in pathophysiology of major depression.
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In a recent study, patients with depression showed a significantly higher tryptophan breakdown index and lower kynurenic acid concentration level compared with the normal population.
“In a recent study[49], patients with depression showed a significantly higher tryptophan breakdown index and lower kynurenic acid concentration level compared with those in the normal population.”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [49]
Neurodegeneration in brain regions including the hippocampus and frontal lobe results in cognitive and memory impairments, inhibits brain strategies that might cope with stress, and induces depression or treatment-resistant depression.
“Neurodegeneration in brain regions including the hippocampus and frontal lobe results in cognitive and memory impairments. As a result, the neurodegeneration process inhibits all of the brain strategies that might cope with the stress, which induces depression or treatment-resistant depression.”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [49]
These findings imply that patients with depression exhibit decreased levels of neuroprotection markers, which supports the neurodegeneration hypothesis.
“These findings imply that patients with depression exhibit decreased levels of neuroprotection markers, which supports the neurodegeneration hypothesis.”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [49]
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Self-citation
- Authors
- Myint, A.-M., Kim, Y. K., Verkerk, R., Scharpé, S., Steinbusch, H., & Leonard, B.
- Affiliations
- University of Antwerp (BE)
- Korea University Medical Center (KR)
- Maastricht University (NL)
- Corresponding author
- Myint, Aye-Mu
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 98
- Issue
- 1-2
- Pages
- 143-151
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2115430420
- Cited by
- 527
- References
- 70
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 25 · 2023: 16 · 2022: 28 · 2021: 34 · 2020: 36 · 2019: 34 · 2018: 36 · 2017: 23 · 2016: 38 · 2015: 47 · 2014: 22 · 2013: 33 · 2012: 29
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universiteit Antwerpen
- 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, neuroprotection, neurodegeneration, tryptophan metabolism, kynurenic acid, plasma biomarkers, first-episode depression, depression pathophysiology
- MeSH terms
- Adult, Depressive Disorder, Female, Humans, Kynurenine, Male, Middle Aged, Psychiatric Status Rating Scales, Tryptophan, Neuroprotective Agents
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