The DOI matches its Crossref record; 62 of the 63 references it cites were found in a registry or an index.
NMDA receptor hypofunction model of schizophrenia
Abstract
Several decades of research attempting to explain schizophrenia in terms of the dopamine hyperactivity hypothesis have produced disappointing results. A new hypothesis focusing on hypofunction of the NMDA glutamate transmitter system is emerging as a potentially more promising concept. In this article, we present a version of the NMDA receptor hypofunction hypothesis that has evolved from our recent studies pertaining to the neurotoxic and psychotomimetic effects of PCP and related NMDA antagonist drugs. In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested.
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“This results in disinhibition and hyperactivity of excitatory pathways, which will eventually cause neuronal damage.17”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [17]
In the citing paper
“The NMDA-receptor hypofunction hypothesis was evolved from studies with NMDA-receptor antagonists, such as PCP and ketamine.17”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [17]
In the citing paper
“In fact, diminished glutamate receptor activation, in particular of the NMDA-type of glutamate receptor, may be a possible underlying mechanism of reduced synaptic activity because NMDA-receptor antagonists produce the same symptoms as those seen in schizophrenia.17,18,25”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [17]
In the citing paper
“This hypothesis receives some support from animal models of schizophrenia (36), based on pharmacologically induced, excitatory amino acid toxicity that preferentially (but without explanation to date) targets this area.”
From A default mode of brain function (2001) · cites this paper as [36]
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Cited by
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Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568
General Anesthesia, Sleep, and Coma
Brown, E. N., Lydic, R., & Schiff, N. D. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0808281 · Cited by 1,413
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Metadata
- Authors
- Olney, J. W., Newcomer, J. W., & Farber, N. B.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Olney, John W
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 33
- Issue
- 6
- Pages
- 523-533
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2084120702
- Cited by
- 1,020
- References
- 63
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 25 · 2023: 23 · 2022: 24 · 2021: 30 · 2020: 32 · 2019: 33 · 2018: 28 · 2017: 46 · 2016: 29 · 2015: 50 · 2014: 56 · 2013: 38 · 2012: 55
- FWCI
- 11.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02mh001510-05, 5k20da000290-05)
- National Institute of Mental Health (MH33894, MH-01510)
- National Institute on Drug Abuse (DA00290)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, NMDA receptor hypofunction, phencyclidine, NMDA receptor antagonists, neurotoxicity, psychotomimetic effects, schizophrenia treatment
- MeSH terms
- Animals, Disease Models, Animal, Enzyme Inhibitors, Humans, Models, Biological, Models, Psychological, Phencyclidine, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Rats
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