COX-2 inhibition in schizophrenia and major depression.

Abstract

In schizophrenia and depression, opposite patterns of type-1 - type-2 immune response seem to be associated with differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan - kynurenine metabolism resulting in increased production of kynurenic acid in schizophrenia and decreased production of kynurenic acid in depression. These differences are associated with an imbalance in the glutamatergic neurotransmission, which may contribute to an overweight of N-methyl-D-aspartate (NMDA) agonism in depression and of NMDA antagonism in schizophrenia. The differential activation of microglia cells and astrocytes may be an additional mechanism contributing to this imbalance. The immunological imbalance results both in schizophrenia and in depression in an increased Prostaglandin E(2) (PGE(2)) production and probably also in an increased Cyclo-oxygenase-2 (COX-2) expression. Although there is strong evidence for the view, that the interactions of the immune system, IDO, the serotonergic system, and the glutamatergic neurotransmission play a key role in schizophrenia and in depression, several gaps, e.g. the roles of genetics, disease course, sex, different psychopathological states, etc. have to be bridged by intense further research. There are already hints that anti-inflammatory therapy may have beneficial effects in schizophrenia and major depression. COX-2 inhibititors have been tested in animal models of depression and in preliminary clinical trials, the latter showing favourable effects compared to placebo, both, in schizophrenia and in major depression. The effects of COX-2 inhibition in the central nervous system (CNS) as well as the different components of the inflammatory system, the kynurenine-metabolism and the glutamatergic neurotransmission, however, still need careful further validation including clinical studies with sufficient sample size.

• Authors: Norbert Müller, Markus J Schwarz
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 14 Issue 14 Pg. 1452-65 ( 2008) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 18537668 (Publication Type: Journal Article, Review)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Cytokines
• Receptors, N-Methyl-D-Aspartate
• Cyclooxygenase 2
• Kynurenic Acid

Topics

• Animals
• Cyclooxygenase 2 (biosynthesis)
• Cyclooxygenase 2 Inhibitors (therapeutic use)
• Cytokines (metabolism)
• Depressive Disorder, Major (immunology, metabolism, therapy)
• Electroconvulsive Therapy
• Humans
• Hypothalamo-Hypophyseal System (physiopathology)
• Inflammation (immunology, metabolism)
• Kynurenic Acid (metabolism)
• Pituitary-Adrenal System (physiopathology)
• Receptors, N-Methyl-D-Aspartate (agonists, antagonists & inhibitors, physiology)
• Schizophrenia (immunology, metabolism, therapy)
• Sleep Deprivation
• Synaptic Transmission