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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In the citing paper
“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]
Citations
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Chapter 17. The Expanding Role of Imaging in Prion Disease
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Chapter 8. New Techniques for Understanding Huntington’s Disease
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Chapter 18. Applications of Functional Imaging to Carbon Monoxide Poisoning
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Chapter 26. The Limbic Thalamus
Taber, K. H., Wen, C., Khan, A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg29
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Chapter 19. Binswanger’s Disease: An Ongoing Controversy
Hurley, R. A., Tomimoto, H., Akiguchi, I., Fisher, R. E., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg21
Chapter 21. Neuropsychiatric Presentation of Multiple Sclerosis
Hurley, R. A., Taber, K. H., Zhang, J., & Hayman, L. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg23
Chapter 3. Ecstasy in the Brain: A Model for Neuroimaging
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Chapter 22. Functional Neuroanatomy of Sleep and Sleep Deprivation
Taber, K. H., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg25
Chapter 11. Blast-Related Traumatic Brain Injury: What Is Known?
Taber, K. H., Warden, D. L., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg13
Chapter 29. An Update on Estrogen: Higher Cognitive Function, Receptor Mapping, Neurotrophic Effects
Taber, K. H., Murphy, D. D., Blurton-Jones, M. M., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg32
Chapter 4. The Future for Diffusion Tensor Imaging in Neuropsychiatry
Taber, K. H., Pierpaoli, C. M., Rose, S., Rugg‐Gunn, F. J., Chalk, J. B., Jones, D. K., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg05
Hurley, R. A., Bradley, W. G., Latifi, H. T., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg22
Chapter 5. Cortical Inhibition in Alcohol Dependence
Taber, K. H., Hurley, R. A., Abi‐Dargham, A., & Bernice Porjesz, A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg06
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Chapter 2. Functional Magnetic Resonance Imaging: Application to Post-Traumatic Stress Disorder
Taber, K. H., Rauch, S. L., Lanius, R. A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg03
Chapter 10. Bipolar Disorder: Imaging State Versus Trait
Friedman, J. N. W., Hurley, R. A., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg12
Chapter 13. Traumatic Axonal Injury: Novel Insights Into Evolution and Identification
Hurley, R. A., McGowan, J. C., Arfanakis, K., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg15
Chapter 23. Neural Underpinnings of Fear and Its Modulation: Implications for Anxiety Disorders
Miller, L. A., Taber, K. H., Gabbard, G. O., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg26
Chapter 24. Rabies and the Cerebellum: New Methods for Tracing Circuits in the Brain
Taber, K. H., Strick, P. L., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg27
Chapter 14. Functional Imaging as a Window to Dementia: Corticobasal Degeneration
Seritan, A. L., Mendez, M. F., Silverman, D. H. S., Hurley, R. A., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg16
Chapter 31. Schizophrenia: What’s Under the Microscope?
Taber, K. H., Lewis, D. A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg35
Chapter 12. Mild Traumatic Brain Injury: Neuroimaging of Sports-Related Concussion
Mendez, C. V., Hurley, R. A., Lassonde, M. C., Zhang, L., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg14
Chapter 9. Sudden Onset Panic: Epileptic Aura or Panic Disorder?
Hurley, R. A., Fisher, R. E., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg11
Hurley, R. A., Ernst, T., Khalili, K., Valle, L. D., Simone, I. L., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg18
Chapter 28. Functional Anatomy of Central Pain
Taber, K. H., Rashid, A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg31
Chapter 1. Blood Flow Imaging of the Brain: 50 Years’ Experience
Taber, K. H., BLACK, K. J., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg02
Chapter 25. Conversion Hysteria: Lessons From Functional Imaging
Black, D. N., Seritan, A. L., Taber, K. H., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg28
Chapter 6. Application of Magnetoencephalography to the Study of Autism
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Johnson, P. A., Hurley, R. A., Benkelfat, C., Herpertz, S. C., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg30
Chapter 30. Predicting Treatment Response in Obsessive-Compulsive Disorder
Hurley, R. A., Saxena, S., Rauch, S. L., Hoehn‐Saric, R., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg34
Chapter 15. Metachromatic Leukodystrophy: A Model for the Study of Psychosis
Black, D. N., Taber, K. H., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg17
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Chapter 32. Surgical Treatment of Mental Illness: Impact of Imaging
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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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