title: Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis.
abstract: Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the kynurenine pathway of tryptophan degradation. Evidence suggests that abnormal KYNA levels are involved in the pathophysiology of schizophrenia. However, this has never been assessed through a meta-analysis. A literature search was conducted through Ovid using Embase, Medline, and PsycINFO databases (last search: December 2016) with the search terms: (kynuren* or KYNA) and (schizophreni* or psychosis). English language studies measuring KYNA levels using any method in patients with schizophrenia and healthy controls (HCs) were identified. Standardized mean differences (SMDs) were calculated to determine differences in KYNA levels between groups. Subgroup analyses were separately performed for nonoverlapping participant samples, KYNA measurement techniques, and KYNA sample source. The influences of patients' age, antipsychotic status (%medicated), and sex (%male) on study SMDs were assessed through a meta-regression. Thirteen studies were deemed eligible for inclusion in the meta-analysis. In the main analysis, KYNA levels were elevated in the patient group. Subgroup analyses demonstrated that KYNA levels were increased in nonoverlapping participant samples, and centrally (cerebrospinal fluid and brain tissue) but not peripherally. Patients' age, %medicated, and %male were each positively associated with study SMDs. Overall, KYNA levels are increased in patients with schizophrenia, specifically within the central nervous system. An improved understanding of KYNA in patients with schizophrenia may contribute to the development of novel diagnostic approaches and therapeutic strategies.
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Neuropsychiatry, Keio University, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Department of Neuropsychiatry, Keio University, Tokyo, Japan.|Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.|Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Institute Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Institute Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007736:Kynurenic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D012559:Schizophrenia / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D007736:Kynurenic Acid
keywords: kynurenine; neuroinflammation; psychosis; tryptophan