title: A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction.
abstract: There is mounting evidence of a glutamate dysfunction in schizophrenia, as suggested by the fact that schizophrenia and phencyclidine psychosis are similar and phencyclidine is known to block the N-methyl-D-aspartate (NMDA) subtypes of glutamate. Both occur mainly after puberty, suggesting they may share similar underlying developmental processes. Direct evidence is now accumulating from the study of messenger RNA that glutamate receptor deficiencies occur in schizophrenia and are regionally and specifically distributed. These results find support from studies of memory, electrophysiological findings, clinical treatment, and pharmacological studies in mammals and humans. Our recent findings of: a) a marked decrease in pyramidal cell dendritic spines in layer III of the frontal and temporal cortex, and b) a greater than 0.90 correlation between decrease in mRNA for the NMDA glutamate receptor and cognitive deterioration in elderly schizophrenics, present the strongest evidence to date that glutamate dysfunction plays an important role in schizophrenia.
authors.affiliation: Charing Cross & Westminster Medical School, University of London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Hirsch
authors.forename: I
authors.initials: I
authors.lastname: Das
authors.forename: L J
authors.initials: LJ
authors.lastname: Garey
authors.forename: J
authors.initials: J
authors.lastname: de Belleroche
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D012565:Schizophrenic Psychology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid