A Neurodegenerative Hypothesis of Cytokine-Serotonin Interaction in Major Depression.
- Author:
Yong Ku KIM
1
Author Information
1. Department of Psychiatry, Korea University College of Medicine, Ansan Hospital, Ansan, Korea. yongku@korea.ac.kr
- Publication Type:Original Article
- Keywords:
Serotonin;
Cytokine;
Neurogenesis;
Neurodegeneration;
IDO;
Depression
- MeSH:
Autoreceptors;
Brain;
Cytokines;
Depression*;
Dinoprostone;
Interleukin-1;
Interleukin-10;
Interleukin-12;
Interleukin-2;
Interleukin-4;
Interleukin-6;
Kynurenic Acid;
Kynurenine;
N-Methylaspartate;
Neurogenesis;
Quinolinic Acid;
Serotonin;
Tryptophan;
Tumor Necrosis Factor-alpha
- From:Journal of Korean Neuropsychiatric Association
2004;43(4):386-392
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
A growing body of evidence suggests that major depression is associated with increased productions of pro-inflammatory cytokines such as IL-1, IL-6, IL-12 or TNF-alpha and increased concentrations of prostaglandin E2 and negative-regulatory cytokines such as IL-4 or IL-10. In major depression, interactions among brain 5-HT levels, the activity of its autoreceptors, and that of postsynaptic receptors play a critical role in mood changes and depression. Recently, the link between cytokines and serotonergic turnover has been explored. Cytokines such as IL-1, IL-2 and IFN-gamma reduce the production of 5-HT by stimulating the activity of indoleamine-2,3 dioxygenase (IDO), an enzyme which convert tryptophan, the precursor of 5-HT to kynurenine. The kynurenine is metabolized into quinolinic acid (quinolinate) and kynurenic acid (kynurenate), an excitotoxic NMDA receptor agonist and the antagonist of three ionotropic excitotatory aminoacid receptors, respectively. The cytokineserotonin interaction through IDO that leads to the challenge between quinolinate and kynurenate in the brain may finally induce the neurodegeneration in depression. The neurodegeneration hypothesis of depression can explain how people cope with psychological or physical stress at different stages according to severity and duration of stress and why major depression develops.
