title: [The kynurenic acid hypothesis - a new look at etiopathogenesis and treatment of schizophrenia].
abstract: Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan formed in the brain and in the periphery, known to block ionotropic glutamate receptors and α7 nicotinic receptors, and to act as a ligand of G protein-coupled GPR35 receptors and human aryl hydrocarbon (AHR) receptors. KYNA seems to modulate a number of mechanisms involved in the pathogenesis of schizophrenia including dopaminergic transmission in mesolimbic and mesocortical areas or glutamatemediated neurotransmission. The kynurenine hypothesis of schizophrenia links the occurrence of positive and negative symptoms of schizophrenia and cognitive impairments characteristic for the disease with the disturbances of kynurenine pathway function. Available data suggest that antipsychotic drugs may restore balance among kynurenine pathway metabolites, and that co-administration of glycine with antipsychotics may reduce extrapyramidal symptoms in patients suffering from schizophrenia. Central level of KYNA may increase in the course of inflammation, which is consistent with the inflammatory hypothesis of schizophrenia. Alterations of immune response and disturbed functioning of kynurenine pathway may lead to disproportion between neuroprotective and neurotoxic mechanisms in the brain. Currently, intense research efforts are focused on the role of kynurenine pathway metabolites in pathogenesis of schizophrenia, their association with the response to antipsychotic treatment, and search for novel medications modulating the function of kynurenine pathway.
authors.affiliation: I Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin.
authors.forename: Marta
authors.initials: M
authors.lastname: Flis
authors.affiliation: Mental Health Outpatient Clinic, Children's University Hospital, Medical University of Lublin.
authors.forename: Kinga
authors.initials: K
authors.lastname: Szymona
authors.affiliation: Department of Clinical Neuropsychiatry, Medical University of Lublin.
authors.forename: Justyna
authors.initials: J
authors.lastname: Morylowska-Topolska
authors.affiliation: II Departament of Psychiatry and Psychiatry Rehabilitation, Medical University of Lublin.
authors.forename: Anna
authors.initials: A
authors.lastname: Urbańska
authors.affiliation: Department of Clinical Neuropsychiatry, Medical University of Lublin.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krukow
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University in Lublin.
authors.forename: Martyna
authors.initials: M
authors.lastname: Kandefer-Szerszeń
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University in Lublin.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zdzisińska
authors.affiliation: Laboratory of Cellular and Molecular Pharmacology, Department of Experimental and Clinical Pharmacology, Medical University of Lublin.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Urbańska
authors.affiliation: I Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin; II Departament of Psychiatry and Psychiatry Rehabilitation, Medical University of Lublin.
authors.forename: Hanna
authors.initials: H
authors.lastname: Karakuła-Juchnowicz
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007736:Kynurenic Acid / Q000378:metabolism / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D051792:Basic Helix-Loop-Helix Proteins; D007736:Kynurenic Acid; D018733:Nicotinic Antagonists; D018336:Receptors, Aryl Hydrocarbon; D058468:Receptors, Ionotropic Glutamate; D011978:Receptors, Nicotinic; C111235:AHR protein, human
keywords: inflammatory processes; kynurenic acid; schizophrenia