title: Imbalanced kynurenine pathway in schizophrenia.
abstract: Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magdalena E
authors.initials: ME
authors.lastname: Kegel
authors.affiliation: AstraZeneca, Research and Development, Innovative Medicines, Personalised Healthcare and Biomarkers, Translational Science Centre, Science for Life Laboratory, Solna, Sweden. ; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bhat
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Psychiatry, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Skogh
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Psychiatry, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Samuelsson
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Psychiatry, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lundberg
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Sellgren
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lilly
authors.initials: L
authors.lastname: Schwieler
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Engberg
authors.affiliation: AstraZeneca, Research and Development, Innovative Medicines, Personalised Healthcare and Biomarkers, Translational Science Centre, Science for Life Laboratory, Solna, Sweden. ; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ina
authors.initials: I
authors.lastname: Schuppe-Koistinen
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Erhardt
keywords: NMDA receptor; cerebrospinal fluid; inflammation; kynurenic acid; psychosis; quinolinic acid