Cited by 1,685Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.

Glutamate Receptor Dysfunction and Schizophrenia

Olney, John W.·1995·Archives of General Psychiatry

Abstract

In this article, we advance a unified hypothesis pertaining to combined dysfunction of dopamine and N-methyl-D-aspartate glutamate receptors that highlights N-methyl-D-aspartate receptor hypofunction as a key mechanism that can help explain major clinical and pathophysiological aspects of schizophrenia. The following fundamental features of schizophrenia are accommodated by this hypothesis: (1) the occurrence of structural brain changes during early development that have the potential for producing subsequent clinical manifestations of schizophrenia, (2) a quiescent period in infancy and adolescence before clinical manifestations are expressed, (3) onset in early adulthood of psychotic symptoms, (4) involvement of dopamine (D2) receptors in some cases but not others that would explain why some but not all patients are responsive to typical neuroleptic therapy, and (5) ongoing neurodegenerative changes and cognitive deterioration in some patients. We propose that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents (clozapine, olanzapine, fluperlapine), a better understanding of the N-methyl-D-aspartate receptor hypofunction mechanism and ways of preventing its neurodegenerative consequences in the rat brain may lead to improved pharmacotherapy in schizophrenia.

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Crossref · 10.1001/archpsyc.1995.03950240016004

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Metadata

Authors
Olney, J. W.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Olney, John W.
Venue
Archives of General Psychiatry
Published
1995-12-01
Volume
52
Issue
12
Pages
998
ISSN
0003-990X (ISSN-L)
OpenAlex
W2093248761
Cited by
1,685
References
99
Citations by year
2026: 20 · 2025: 13 · 2024: 17 · 2023: 23 · 2022: 35 · 2021: 37 · 2020: 44 · 2019: 49 · 2018: 37 · 2017: 49 · 2016: 51 · 2015: 52 · 2014: 53 · 2013: 54 · 2012: 62
FWCI
45.32
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r01da006454-01)
  • National Institute on Drug Abuse (R01DA005072, DA07261, DA05072, T32DA007261, DA 06454)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
schizophrenia, NMDA receptor hypofunction, dopamine D2 receptor, psychosis, atypical antipsychotics, clozapine, olanzapine, neurodegeneration, brain development, cognitive decline
MeSH terms
Animals, Brain, Gyrus Cinguli, Microscopy, Electron, Models, Neurological, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Pyramidal Cells, Rats

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