Glutamatergic mechanisms in schizophrenia

Tsai, Guochuan; Coyle, Joseph T.

doi:10.1146/annurev.pharmtox.42.082701.160735

Cited by 577Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Glutamatergic mechanisms in schizophrenia

Tsai, Guochuan, Coyle, Joseph T.·2002·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev.pharmtox.42.082701.160735

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Abstract

Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving typical antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.

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The resemblance between patient contrast response curves and NMDA antagonist effects is consistent with glutamatergic theories of schizophrenia.
“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 [25]
The decreased slope at low contrast and decreased plateau in patients closely resembles results seen after microinfusion of an NMDA antagonist into cat LGN and visual cortex.
“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 [25]

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Authors: Tsai, G., & Coyle, J. T.
Affiliations: Harvard University (US)
ORCID: Tsai, Guochuan
Coyle, Joseph T.
Venue: Annual Review of Pharmacology and Toxicology
Publisher: Annual Reviews
Published: 2002-04
Volume: 42
Issue: 1
Pages: 165-179
ISSN: 0362-1642 (ISSN-L)
1545-4304
DOI: 10.1146/annurev.pharmtox.42.082701.160735
OpenAlex: W2108610913
Cited by: 577
References: 139
Citations by year: 2026: 7 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 11 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 15 · 2015: 23 · 2014: 29 · 2013: 23 · 2012: 28
FWCI: 7.03
Type: journal article
Language: en
Open access: closed
Locations: The Annual Review of Pharmacology and Toxicology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (R01MH051290, MH 51290, MH606450)
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, glutamatergic mechanisms, NMDA receptor hypofunction, negative symptoms, cognitive impairment, ketamine, phencyclidine, antipsychotic drugs, dopamine D2 receptor antagonists
MeSH terms: Animals, Dopamine, Humans, Phencyclidine, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Glutamic Acid

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Glutamatergic mechanisms in schizophrenia

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