TY - JOUR
T1 - Glutamate-mediated excitotoxicity in schizophrenia
T2 - A review
AU - Plitman, Eric
AU - Nakajima, Shinichiro
AU - de la Fuente-Sandoval, Camilo
AU - Gerretsen, Philip
AU - Chakravarty, M. Mallar
AU - Kobylianskii, Jane
AU - Chung, Jun Ku
AU - Caravaggio, Fernando
AU - Iwata, Yusuke
AU - Remington, Gary
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
E.P. has received funding from the Ontario Graduate Scholarship. S.N. has received fellowship grant awards from the Centre for Addiction and Mental Health, Japan Society for the Promotion of Science, Canadian Institute of Health Research, and manuscript fees from Dainippon Sumitomo Pharma and Kyowa Hakko Kirin. C.D. has received grant support from Janssen (Johnson & Johnson), and has served as a consultant and/or speaker for AstraZeneca, Eli Lilly and Janssen. P.G. has received fellowship awards from the Centre for Addiction and Mental Health and the Ontario Mental Health Foundation. Y.I. has received manuscript fees from Wiley Japan. G.R. has received research support from the Canadian Diabetes Association, the Canadian Institutes of Health Research, Medicure, Neurocrine Biosciences, Novartis, Research Hospital Fund–Canada Foundation for Innovation, and the Schizophrenia Society of Ontario and has served as a consultant or speaker for Novartis, Laboratorios Farmacéuticos Rovi, Synchroneuron, and Roche. A.G. has received grant support from US National Institute of Health, Canadian Institute of Health Research, Ontario Mental Health Foundation, CONACyT, ICyTDF, NARSAD, Research Hospital Fund–Canada Foundation for Innovation, Ministry of Economic Development and Innovation of Ontario and Janssen-Cilag. He has served as a consultant for Abbott Laboratories, Gedeon Richter Plc, and Eli Lilly. M.C., Ja.K., Ju.K and F.C. have no conflicts of interest to report.
Funding Information:
The work was partially supported by a NARSAD Independent Investigator Grant from the Brain and Behavioural Research Foundation (A.G.), the Canadian Institute of Health Research MOP-114989 (A.G.), the Ontario Graduate Scholarship (E.P.) and the Early Researcher Award, Ministry of Economic Development and Innovation of Ontario (A.G., Y.I.). These sources were not involved in the collection, analysis and interpretation of data, the writing of the report or in the decision to submit the paper for publication.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Findings from neuroimaging studies in patients with schizophrenia suggest widespread structural changes although the mechanisms through which these changes occur are currently unknown. Glutamatergic activity appears to be increased in the early phases of schizophrenia and may contribute to these structural alterations through an excitotoxic effect. The primary aim of this review was to describe the possible role of glutamate-mediated excitotoxicity in explaining the presence of neuroanatomical changes within schizophrenia. A Medline® literature search was conducted, identifying English language studies on the topic of glutamate-mediated excitotoxicity in schizophrenia, using the terms "schizophreni*" and "glutam*" and (("MRS" or "MRI" or "magnetic resonance") or ("computed tomography" or "CT")). Studies concomitantly investigating glutamatergic activity and brain structure in patients with schizophrenia were included. Results are discussed in the context of findings from preclinical studies. Seven studies were identified that met the inclusion criteria. These studies provide inconclusive support for the role of glutamate-mediated excitotoxicity in the occurrence of structural changes within schizophrenia, with the caveat that there is a paucity of human studies investigating this topic. Preclinical data suggest that an excitotoxic effect may occur as a result of a paradoxical increase in glutamatergic activity following N-methyl-d-aspartate receptor hypofunction. Based on animal literature, glutamate-mediated excitotoxicity may account for certain structural changes present in schizophrenia, but additional human studies are required to substantiate these findings. Future studies should adopt a longitudinal design and employ magnetic resonance imaging techniques to investigate whether an association between glutamatergic activity and structural changes exists in patients with schizophrenia.
AB - Findings from neuroimaging studies in patients with schizophrenia suggest widespread structural changes although the mechanisms through which these changes occur are currently unknown. Glutamatergic activity appears to be increased in the early phases of schizophrenia and may contribute to these structural alterations through an excitotoxic effect. The primary aim of this review was to describe the possible role of glutamate-mediated excitotoxicity in explaining the presence of neuroanatomical changes within schizophrenia. A Medline® literature search was conducted, identifying English language studies on the topic of glutamate-mediated excitotoxicity in schizophrenia, using the terms "schizophreni*" and "glutam*" and (("MRS" or "MRI" or "magnetic resonance") or ("computed tomography" or "CT")). Studies concomitantly investigating glutamatergic activity and brain structure in patients with schizophrenia were included. Results are discussed in the context of findings from preclinical studies. Seven studies were identified that met the inclusion criteria. These studies provide inconclusive support for the role of glutamate-mediated excitotoxicity in the occurrence of structural changes within schizophrenia, with the caveat that there is a paucity of human studies investigating this topic. Preclinical data suggest that an excitotoxic effect may occur as a result of a paradoxical increase in glutamatergic activity following N-methyl-d-aspartate receptor hypofunction. Based on animal literature, glutamate-mediated excitotoxicity may account for certain structural changes present in schizophrenia, but additional human studies are required to substantiate these findings. Future studies should adopt a longitudinal design and employ magnetic resonance imaging techniques to investigate whether an association between glutamatergic activity and structural changes exists in patients with schizophrenia.
KW - Excitotoxicity
KW - Glutamate
KW - Glutamine
KW - MRS
KW - Psychosis
KW - Schizophrenia
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U2 - 10.1016/j.euroneuro.2014.07.015
DO - 10.1016/j.euroneuro.2014.07.015
M3 - Review article
C2 - 25159198
AN - SCOPUS:84907983364
VL - 24
SP - 1591
EP - 1605
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
IS - 10
ER -