The new ‘5-HT’ hypothesis of depression: Cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression

@article{Maes2011TheN,
  title={The new ‘5-HT’ hypothesis of depression: Cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression},
  author={Michael Maes and Brian E. Leonard and Aye Mu Myint and Marta Kubera and Robert Verkerk},
  journal={Progress in Neuro-Psychopharmacology and Biological Psychiatry},
  year={2011},
  volume={35},
  pages={702-721}
}
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520 Citations
Highly Influential Citations
46
Background Citations
222
Methods Citations
4
Results Citations
9

520 Citations

Somatization, but not depression, is characterized by disorders in the tryptophan catabolite (TRYCAT) pathway, indicating increased indoleamine 2,3-dioxygenase and lowered kynurenine aminotransferase activity.
TLDR
Somatization is characterized by increased IDO activity and disorders in KAT activity and an increased neurotoxic potential, and the TRYCAT pathway may play a role in the pathophysiology of somatizing and "psychosomatic" symptoms.
Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression
Schizophrenia is primed for an increased expression of depression through activation of immuno-inflammatory, oxidative and nitrosative stress, and tryptophan catabolite pathways
Activation of Brain Indoleamine-2,3-dioxygenase Contributes to Depressive-Like Behavior Induced by an Intracerebroventricular Injection of Streptozotocin in Mice
TLDR
Evidence that IDO plays a critical role in mediating inflammation-induced depression is provided and the notion that neuroinflammation and the kynurenine pathway are important targets for novel therapeutic drugs for depression is supported.
Indoleamine-2,3-Dioxygenase/Kynurenine Pathway as a Potential Pharmacological Target to Treat Depression Associated with Diabetes
TLDR
The hypothesis that neuroinflammation in the HIP followed by IDO activation with a consequent decrease in the 5-HT levels can be a possible pathophysiological mechanism that links depression to diabetes is supported.
Poly I:C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression
IDO chronic immune activation and tryptophan metabolic pathway: A potential pathophysiological link between depression and obesity
Indoleamine-2,3-dioxygenase mediates neurobehavioral alterations induced by an intracerebroventricular injection of amyloid-β1-42 peptide in mice
Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine.
  • Hai-Quyen TranE. Shin Hyoung‐Chun Kim
  • Biology, Psychology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2019
Plasma indoleamine-2,3-dioxygenase (IDO) is increased in drug-naïve major depressed patients and treatment with sertraline and ketoprofen normalizes IDO in association with pro-inflammatory and immune-regulatory cytokines.
TLDR
MDD is accompanied by activated immune-inflammatory pathways (including IDO) and the compensatory immune-regulatory system (CIRS), and the clinical efficacy of antidepressant treatment may be ascribed at least in part to decrements in IDO and the immune- inflammatory response.
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References

SHOWING 1-10 OF 292 REFERENCES
The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation.
TLDR
It is concluded that kynurenine, kynurenic acid, and xanthurenic Acid have anti-inflammatory effects trough a reduction of IFNgamma, whereas quinolinic acid has pro- inflammatory effects in particular via significant decreases in IL-10.
The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression.
The mechanisms by which administration of interferon-alpha induces neuropsychiatric side effects, such as depressive symptoms and changes in cognitive function, are not clear as yet. Direct influence…
Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice
TLDR
A direct molecular link between Trp metabolism and neurogenesis and anxiety-related behavior under physiological conditions is demonstrated.
The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression.
  • M. Maes
  • Biology
    Neuro endocrinology letters
  • 2008
This paper hypothesizes that inflammatory, oxidative and nitrosative (IO&NS) pathways, and an increased translocation of LPS from gram-negative bacteria are causally related to depression following…
Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression.
CSF Concentrations of Brain Tryptophan and Kynurenines during Immune Stimulation with IFN-alpha: Relationship to CNS Immune Responses and Depression
TLDR
Peripheral administration of IFN-α activated IDO in concert with central cytokine responses, resulting in increased brain KYN and QUIN, which correlated with depressive symptoms.
Interferon-γ and Tumor Necrosis Factor-α Mediate the Upregulation of Indoleamine 2,3-Dioxygenase and the Induction of Depressive-Like Behavior in Mice in Response to Bacillus Calmette-Guérin
TLDR
It is demonstrated that IFNγ, with TNFα, is necessary for induction of IDO and depressive-like behavior in mice after BCG infection and synergized to induce IDO in primary microglia.
Peripheral and cerebral metabolic abnormalities of the tryptophan–kynurenine pathway in a murine model of major depression
Indoleamine 2,3-dioxygenase, an immunomodulatory protein, is suppressed by (-)-epigallocatechin-3-gallate via blocking of gamma-interferon-induced JAK-PKC-delta-STAT1 signaling in human oral cancer cells.
TLDR
EGCG, the major constituent of green tea, is found to significantly inhibit the expression of IDO in human oral cancer cell lines, indicating that EGCG is a potential drug for immune and target therapy to enhance cancer therapy by increasing antitumor immunity.
Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: A role for IFN-γ?
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