title: Inflammation and the glutamate system in schizophrenia: implications for therapeutic targets and drug development.
abstract: BACKGROUND
  Despite the progress in antipsychotic therapy for schizophrenia, the effects are still not satisfactory. There is a high percentage of therapy-resistant patients and the overall course of the disease is unfavourable in many affected individuals. Therefore, other therapeutic targets than dopaminergic and serotonergic neurotransmitters are being considered.
  
  
  OBJECTIVE
  Glutamatergic hypofunction, mediated mainly by NMDA receptor blockade, is suggested to be indirectly responsible for dopaminergic dysfunction in schizophrenia. Increased levels of kynurenic acid (KYN-A), an endogenous NMDA receptor antagonist, resulting from disturbed tryptophan/kynurenine metabolism can explain psychotic symptoms and cognitive deterioration.
  
  
  METHODS
  The role of the immune system in the production of KYN-A and therapeutic targets in the immune and glutamate systems are outlined.
  
  
  CONCLUSIONS
  Therapeutic consequences are discussed. Glutamate modulators that particularly influence the NMDA co-transmitters glycine and serine, including inhibitors of glycine transporters, are described and initial clinical evidence is discussed. Another target of the glutamate system is the metabotropic mGlu2/3 receptor; Preliminary clinical results of a study with a mGlu2/3 receptor agonist in schizophrenia are mentioned.
authors.affiliation: Ludwig-Maximilians-University, Hospital for Psychiatry and Psychotherapy, Nussbaumstr 7, 80336 Munich, Germany. Norbert.Mueller@med.uni-muenchen.de
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid