J Korean Neuropsychiatr Assoc.  2004 Jul;43(4):386-392.

A Neurodegenerative Hypothesis of Cytokine-Serotonin Interaction in Major Depression

• Kim YK

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.

Keyword

Serotonin; Cytokine; Neurogenesis; Neurodegeneration; IDO; Depression

MeSH Terms

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
Autoreceptors
Cytokines
Dinoprostone
Interleukin-1
Interleukin-10
Interleukin-12
Interleukin-2
Interleukin-4
Interleukin-6
Kynurenic Acid
Kynurenine
N-Methylaspartate
Quinolinic Acid
Serotonin
Tryptophan
Tumor Necrosis Factor-alpha