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
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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In the citing paper
“In recent years, however, increasing evidence supports dysfunction of the glutaminergic system as being the primary pathophysiological changes seen in schizophrenia [105].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [105]
In the citing paper
“The decreased slope at low contrast and decreased plateau in patients closely resembles results seen after microinfusion of an NDMA antagonist into cat LGN and visual cortex (16,17) (Figure 3A and 3B), consistent with glutamatergic theories of schizophrenia (23–25).”
From Visual perception and its impairment in schizophrenia (2008) · cites this paper as [24]
In the citing paper
“The decreased slope at low contrast and decreased plateau in patients closely resembles results seen after microinfusion of an NDMA antagonist into cat LGN and visual cortex (16,17) (Figure 3A and 3B), consistent with glutamatergic theories of schizophrenia (23–25).”
From Visual perception and its impairment in schizophrenia (2008) · cites this paper as [24]
Citations
Cites
Clozapine for the Treatment-Resistant Schizophrenic: A Double-blind Comparison With Chlorpromazine
Kane, J. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800330013001 · Cited by 4,156
Implications of Normal Brain Development for the Pathogenesis of Schizophrenia
Weinberger, D. R. (1987) · Archives of General Psychiatry · doi:10.1001/archpsyc.1987.01800190080012 · Cited by 3,724
Krystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330
Recent advances in the phencyclidine model of schizophrenia
(1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.10.1301 · Cited by 2,904
Ketamine—its pharmacology and therapeutic uses
white, P. F., Way, W. L., & Trevor, A. J. (1982) · Anesthesiology · doi:10.1097/00000542-198202000-00007 · Cited by 1,474
CEREBRAL VENTRICULAR SIZE AND COGNITIVE IMPAIRMENT IN CHRONIC SCHIZOPHRENIA
Johnstone, E., Frith, C., Crow, T. J., Husband, J., & Kreel, L. (1976) · The Lancet · doi:10.1016/s0140-6736(76)90890-4 · Cited by 1,253
Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs
Olney, J. W., Labruyere, J., & Price, M. T. (1989) · Science · doi:10.1126/science.2660263 · Cited by 1,250
Self-citationAdult Schizophrenia Following Prenatal Exposure to an Influenza Epidemic
Mednick, S. A. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800260109013 · Cited by 1,203
Abnormalities of the Left Temporal Lobe and Thought Disorder in Schizophrenia
Shenton, M. E., Kikinis, R., Jolesz, F. A., Pollak, S. D., LeMay, M. J., Wible, C. G., Hokama, H., Martin, J., Metcalf, D., Coleman, M., et al. (1992) · New England Journal of Medicine · doi:10.1056/nejm199208273270905 · Cited by 1,179
The current status of the dopamine hypothesis of schizophrenia
Carlsson, A. C. (1988) · Neuropsychopharmacology · doi:10.1016/0893-133x(88)90012-7 · Cited by 959
Cited by
Sorted by citations
Items 101–104 of 104
van Berckel, B. N. M., Kegeles, L. S., Waterhouse, R., Guo, N., Hwang, D.-R., Huang, Y., Narendran, R., Van Heertum, R., & Laruelle, M. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300902 · Cited by 43
Neugebauer, N. M., Miyauchi, M., Sato, T., Tadano, J., Akal, H., Ardehali, H., & Meltzer, H. Y. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.12.033 · Cited by 7
Rosoklija, G., Toomayan, G., Ellis, S. P., Keilp, J., Mann, J. J., Latov, N., Hays, A. P., & Dwork, A. J. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.4.349 · Cited by 1
Mathalon, D. H., Sullivan, E. V., Lim, K. O., & Pfefferbaum, A. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.2.148
Metadata
- Authors
- Olney, J. W.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Olney, John W.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- 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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