PT  - JOURNAL ARTICLE
AU  - Marieke C. Wichers
AU  - Michael Maes
TI  - The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-α-induced depression
DP  - 2004 Jan 01
TA  - Journal of Psychiatry and Neuroscience
PG  - 11--17
VI  - 29
IP  - 1
4099  - http://jpn.ca/content/29/1/11.short
4100  - http://jpn.ca/content/29/1/11.full
SO  - JPN2004 Jan 01; 29
AB  - The mechanisms by which administration of interferon-α 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.