Glutamate-mediated excitotoxicity in schizophrenia: a review.

TitleGlutamate-mediated excitotoxicity in schizophrenia: a review.
Publication TypeJournal Article
Year of Publication2014
AuthorsPlitman E, Nakajima S, de la Fuente-Sandoval C, Gerretsen P, M Chakravarty M, Kobylianskii J, Chung JKu, Caravaggio F, Iwata Y, Remington G, Graff-Guerrero A
JournalEur Neuropsychopharmacol
Volume24
Issue10
Pagination1591-605
Date Published2014 Oct
ISSN1873-7862
KeywordsAnimals, Brain, Glutamic Acid, Humans, Receptors, N-Methyl-D-Aspartate, Schizophrenia
Abstract

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.

DOI10.1016/j.euroneuro.2014.07.015
Alternate JournalEur Neuropsychopharmacol
PubMed ID25159198
PubMed Central IDPMC4470624
Grant List114989-1 / / Canadian Institutes of Health Research / Canada