Network beyond IDO in psychiatric disorders: Revisiting neurodegeneration hypothesis
Abstract
The involvement of immune system activation in the pathophysiology of certain psychiatric disorders is well documented. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of the indoleamine 2,3-dioxygenase (IDO) enzyme which is the first rate-limiting enzyme of the tryptophan degradation pathway, the kynurenine pathway. The increased tryptophan degradation could induce serotonin depletion and depressive mood. On the other hand, the downstream metabolites from this pathway, such as 3-hydroxykynurenine, quinolinic acid and kynurenic acid, are neuroactive metabolites which can modulate several neurotransmissions, such as glutamatergic, GABAergic, dopaminergic and noradrenergic neurotransmissions, which in turn induce changes in neuronal-glial network and neuropsychiatric consequences. In this issue, we have revised the previous 'neurodegeneration hypothesis,' which explained the involvement of cytokines and IDO pathway interaction in depression, with a further extended view related to the network beyond IDO, the network between immune molecules, tryptophan metabolites and different neurotransmitters, in depression and other major psychiatric disorders such as schizophrenia, bipolar disorder and childhood psychiatric disorders.
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According to the neurodegeneration hypothesis, acute psychological stress triggers tryptophan defects and mood swings; chronic stress increases proinflammatory cytokines; excessive proinflammatory cytokines activate IDO, accelerate tryptophan metabolism to kynurenine, decrease brain 5-HT, and aggravate depression in vulnerable individuals.
“According to this hypothesis, acute psychological stress triggers tryptophan defects and mood swings. To correct the 5-HT imbalance, 5-HT synthesis and receptor expression are modified. This is the first stage of coping with psychological stress. If the psychological stress is chronic, the levels of proinflammatory cytokines increase.”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [48]
The neurodegeneration hypothesis (cytokine-5-HT interaction) can explain individual differences in depression among the elderly and chronically ill.
“One hypothesis that can explain these differences is the neurodegeneration hypothesis: Cytokine-5-HT interaction[47,48].”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [48]
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- Authors
- Myint, A.-M., & Kim, Y.-K.
- Affiliations
- Maastricht University (NL)
- Korea University (KR)
- Corresponding author
- Myint, Aye-Mu
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 48
- Pages
- 304-313
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2033811826
- Cited by
- 230
- References
- 5
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 10 · 2023: 17 · 2022: 21 · 2021: 25 · 2020: 24 · 2019: 10 · 2018: 21 · 2017: 13 · 2016: 29 · 2015: 30 · 2014: 6
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- EU FP7 European Collaborative Research Project ‘MOODINFLAME’ (22963)
- EU FP7 IAAP/Marie Curie Project ‘Psych-AID’ (286334)
- Advanced Practical Diagnostics, Belgium
- Korea University
- Korea Health 21 R&D
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- indoleamine 2,3-dioxygenase, kynurenine pathway, tryptophan metabolism, neuroinflammation, inflammatory cytokines, depression, 3-hydroxykynurenine, quinolinic acid, kynurenic acid, neurotransmitter modulation, schizophrenia, bipolar disorder, child psychopathology
- MeSH terms
- Mental Disorders, Brain, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase
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