Glutamate-mediated excitotoxicity in schizophrenia: A review

Eric Plitman, Shinichiro Nakajima, Camilo de la Fuente-Sandoval, Philip Gerretsen, M. Mallar Chakravarty, Jane Kobylianskii, Jun Ku Chung, Fernando Caravaggio, Yusuke Iwata, Gary Remington, Ariel Graff-Guerrero

研究成果: Review article査読

103 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1591-1605
ページ数15
ジャーナルEuropean Neuropsychopharmacology
24
10
DOI
出版ステータスPublished - 2014 10月 1

ASJC Scopus subject areas

  • 薬理学
  • 神経学
  • 臨床神経学
  • 精神医学および精神衛生
  • 生物学的精神医学
  • 薬理学(医学)

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