Abstract
The disturbance of the dopaminergic neurotransmission is a key-feature in the neurobiology of schizophrenia. The interaction between the dopaminergic and the glutamatergic neurotransmission, however, attracted more notice to the glutamatergic system. Recent research focussed on factors influencing the glutamatergic neurotransmission. A pro-inflammatory immune state influences the glutamatergic neurotransmission indirectly by its effects on the tryptophan/kynurenine metabolism. The immune response in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and imbalance in the tryptophan/kynurenine metabolism resulting in increased production of kynurenic acid in the brain. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an NMDA antagonism in schizophrenia. The immunological effects of antipsychotics reverse partly the immune imbalance and the unphysiologically enhanced production of the kynurenic acid. These immunological and neurochemical imbalances result in a chronic pro-inflammatory state in association with increased prostaglandin E2 (PGE2) production, increased cyclo-oxygenase-2 (COX-2) expression and increased pro-inflammatory cytokines production and NMDA receptor hypofunctioning. Substances acting directly on the kynurenine metabolism are still in very early stages of development, anti-inflammatory drugs acting indirectly on this metabolism are discussed as therapeutic or preventive agents in schizophrenia. Most of the existing data are related to COX-2 inhibitors, which have been tested in animal experiments and in clinical trials, pointing to favourable effects in schizophrenia.
Keywords: Schizophrenia, tryptophan, kynurenine, immune system psychoneuroimmunology
Current Pharmaceutical Design
Title: Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects
Volume: 17 Issue: 2
Author(s): Norbert Muller, Aye-Mu Myint and Markus J. Schwarz
Affiliation:
Keywords: Schizophrenia, tryptophan, kynurenine, immune system psychoneuroimmunology
Abstract: The disturbance of the dopaminergic neurotransmission is a key-feature in the neurobiology of schizophrenia. The interaction between the dopaminergic and the glutamatergic neurotransmission, however, attracted more notice to the glutamatergic system. Recent research focussed on factors influencing the glutamatergic neurotransmission. A pro-inflammatory immune state influences the glutamatergic neurotransmission indirectly by its effects on the tryptophan/kynurenine metabolism. The immune response in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and imbalance in the tryptophan/kynurenine metabolism resulting in increased production of kynurenic acid in the brain. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an NMDA antagonism in schizophrenia. The immunological effects of antipsychotics reverse partly the immune imbalance and the unphysiologically enhanced production of the kynurenic acid. These immunological and neurochemical imbalances result in a chronic pro-inflammatory state in association with increased prostaglandin E2 (PGE2) production, increased cyclo-oxygenase-2 (COX-2) expression and increased pro-inflammatory cytokines production and NMDA receptor hypofunctioning. Substances acting directly on the kynurenine metabolism are still in very early stages of development, anti-inflammatory drugs acting indirectly on this metabolism are discussed as therapeutic or preventive agents in schizophrenia. Most of the existing data are related to COX-2 inhibitors, which have been tested in animal experiments and in clinical trials, pointing to favourable effects in schizophrenia.
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Cite this article as:
Muller Norbert, Myint Aye-Mu and J. Schwarz Markus, Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects, Current Pharmaceutical Design 2011; 17 (2) . https://dx.doi.org/10.2174/138161211795049552
DOI https://dx.doi.org/10.2174/138161211795049552 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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