The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression

MC Wichers*, M Maes

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

217 Citations (Scopus)

Abstract

The mechanisms by which administration of interferon-a induces neuropsychiatric side effects, such as depressive symptoms and changes in cognitive function, are not clear as yet. Direct influence on serotonergic neurotransmission may contribute to these side effects. In addition, the enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan into kynurenine, may play an important role, first, because IDO activation leads to reduced levels of tryptophan, the precursor of serotonin (5-HT), and thus to reduced central 5-HT synthesis. Second, kynurenine metabolites such as 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QUIN) have toxic effects on brain function. 3-OH-KYN is able to produce oxidative stress by increasing the production of reactive oxygen species (ROS), and QUIN may produce overstimulation of hippocampal N-methyl-D-aspartate (NMDA) receptors, which leads to apoptosis and hippocampal atrophy. Both ROS overproduction and hippocampal atrophy caused by NMDA overstimulation have been associated with depression.

Original languageEnglish
Pages (from-to)11-17
Number of pages7
JournalJournal of psychiatry & neuroscience
Volume29
Issue number1
Publication statusPublished - Jan-2004
Externally publishedYes

Keywords

  • depression
  • interferon-alpha
  • serotonin
  • tryptophan
  • KYNURENINE PATHWAY METABOLISM
  • POSITRON-EMISSION-TOMOGRAPHY
  • QUINOLINIC ACID
  • MAJOR DEPRESSION
  • OXIDATIVE STRESS
  • RAT-BRAIN
  • CEREBROSPINAL-FLUID
  • SICKNESS BEHAVIOR
  • HEPATITIS-C
  • IFN-GAMMA

Cite this