Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis

Eric Plitman, Yusuke Iwata, Fernando Caravaggio, Shinichiro Nakajima, Jun Ku Chung, Philip Gerretsen, Julia Kim, Hiroyoshi Takeuchi, M. Mallar Chakravarty, Gary Remington, Ariel Graff-Guerrero

Research output: Contribution to journalReview article

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)764-777
Number of pages14
JournalSchizophrenia Bulletin
Volume43
Issue number4
DOIs
Publication statusPublished - 2017 Jul 1

Fingerprint

Kynurenic Acid
Meta-Analysis
Schizophrenia
Kynurenine
Nicotinic Receptors
N-Methylaspartate
Tryptophan
Astrocytes
Psychotic Disorders
Antipsychotic Agents
Cerebrospinal Fluid
Language
Central Nervous System

Keywords

  • kynurenine
  • neuroinflammation
  • psychosis
  • tryptophan

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Plitman, E., Iwata, Y., Caravaggio, F., Nakajima, S., Chung, J. K., Gerretsen, P., ... Graff-Guerrero, A. (2017). Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis. Schizophrenia Bulletin, 43(4), 764-777. https://doi.org/10.1093/schbul/sbw221

Kynurenic Acid in Schizophrenia : A Systematic Review and Meta-analysis. / Plitman, Eric; Iwata, Yusuke; Caravaggio, Fernando; Nakajima, Shinichiro; Chung, Jun Ku; Gerretsen, Philip; Kim, Julia; Takeuchi, Hiroyoshi; Chakravarty, M. Mallar; Remington, Gary; Graff-Guerrero, Ariel.

In: Schizophrenia Bulletin, Vol. 43, No. 4, 01.07.2017, p. 764-777.

Research output: Contribution to journalReview article

Plitman, E, Iwata, Y, Caravaggio, F, Nakajima, S, Chung, JK, Gerretsen, P, Kim, J, Takeuchi, H, Chakravarty, MM, Remington, G & Graff-Guerrero, A 2017, 'Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis', Schizophrenia Bulletin, vol. 43, no. 4, pp. 764-777. https://doi.org/10.1093/schbul/sbw221
Plitman, Eric ; Iwata, Yusuke ; Caravaggio, Fernando ; Nakajima, Shinichiro ; Chung, Jun Ku ; Gerretsen, Philip ; Kim, Julia ; Takeuchi, Hiroyoshi ; Chakravarty, M. Mallar ; Remington, Gary ; Graff-Guerrero, Ariel. / Kynurenic Acid in Schizophrenia : A Systematic Review and Meta-analysis. In: Schizophrenia Bulletin. 2017 ; Vol. 43, No. 4. pp. 764-777.
@article{bb9ced2bf9d644038966e0fd93617953,
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.",
keywords = "kynurenine, neuroinflammation, psychosis, tryptophan",
author = "Eric Plitman and Yusuke Iwata and Fernando Caravaggio and Shinichiro Nakajima and Chung, {Jun Ku} and Philip Gerretsen and Julia Kim and Hiroyoshi Takeuchi and Chakravarty, {M. Mallar} and Gary Remington and Ariel Graff-Guerrero",
year = "2017",
month = "7",
day = "1",
doi = "10.1093/schbul/sbw221",
language = "English",
volume = "43",
pages = "764--777",
journal = "Schizophrenia Bulletin",
issn = "0586-7614",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Kynurenic Acid in Schizophrenia

T2 - A Systematic Review and Meta-analysis

AU - Plitman, Eric

AU - Iwata, Yusuke

AU - Caravaggio, Fernando

AU - Nakajima, Shinichiro

AU - Chung, Jun Ku

AU - Gerretsen, Philip

AU - Kim, Julia

AU - Takeuchi, Hiroyoshi

AU - Chakravarty, M. Mallar

AU - Remington, Gary

AU - Graff-Guerrero, Ariel

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - kynurenine

KW - neuroinflammation

KW - psychosis

KW - tryptophan

UR - http://www.scopus.com/inward/record.url?scp=85021819812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021819812&partnerID=8YFLogxK

U2 - 10.1093/schbul/sbw221

DO - 10.1093/schbul/sbw221

M3 - Review article

C2 - 28187219

AN - SCOPUS:85021819812

VL - 43

SP - 764

EP - 777

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

SN - 0586-7614

IS - 4

ER -