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

  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},
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.
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.
Activation of Brain Indoleamine-2,3-dioxygenase Contributes to Depressive-Like Behavior Induced by an Intracerebroventricular Injection of Streptozotocin in Mice
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
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.
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.
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.


The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation.
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
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
CSF Concentrations of Brain Tryptophan and Kynurenines during Immune Stimulation with IFN-alpha: Relationship to CNS Immune Responses and Depression
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
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.
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.
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.