Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to gray matter volume
Open accessAbstract
Background The glutamate model of schizophrenia proposes that altered glutamatergic neurotransmission is fundamental to the development of the disorder. In addition, its potential to mediate neurotoxicity raises the possibility that glutamate dysfunction could underlie neuroanatomic changes in schizophrenia. Here we determine whether changes in brain glutamate are present in subjects at ultra high risk of developing psychosis and whether these changes are related to reductions in cortical gray matter volume.Methods Twenty-seven individuals with an at-risk mental state and a group of 27 healthy volunteers underwent proton magnetic resonance spectroscopy and volumetric proton magnetic resonance imaging using a 3-Tesla scanner. Glutamate and glutamine levels were measured in anterior cingulate, left hippocampus, and left thalamus. These measures were then related to cortical gray matter volume.Results At-risk mental state (ARMS) subjects had significantly lower levels of glutamate than control subjects in the thalamus (p < .05) but higher glutamine in the anterior cingulate (p < .05). Within the ARMS group, the level of thalamic glutamate was directly correlated with gray matter volume in the medial temporal cortex and insula (p < .01).Conclusions This study provides the first evidence that brain glutamate function is perturbed in people with prodromal signs of schizophrenia and that glutamatergic dysfunction is associated with a reduction in gray matter volume in brain regions thought to be critical to the pathogenesis of the disorder. These findings support the hypothesis that drugs affecting the glutamate system may be of benefit in the early stages of psychotic illness.
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Diminished glutamate receptor activation, in particular of the NMDA-type, may be a possible underlying mechanism of reduced synaptic activity because NMDA-receptor antagonists produce the same symptoms as those seen in schizophrenia.
“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 [25]
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- Authors
- Stone, J. M., Day, F., Tsagaraki, H., Valli, I., McLean, M. A., Lythgoe, D. J., O'Gorman, R. L., Barker, G. J., & McGuire, P. K.
- Affiliations
- University of London (GB)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Stone, James M.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 66
- Issue
- 6
- Pages
- 533-539
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1994737820
- Cited by
- 231
- References
- 45
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 13 · 2020: 16 · 2019: 17 · 2018: 11 · 2017: 11 · 2016: 10 · 2015: 20 · 2014: 21 · 2013: 20 · 2012: 21
- FWCI
- 14.60
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- 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
- glutamate dysfunction, glutamatergic neurotransmission, schizophrenia, clinical high risk for psychosis, prodromal psychosis, gray matter volume, glutamine, thalamus, anterior cingulate cortex, hippocampus, insula, neurotoxicity, 1H NMR
- MeSH terms
- Adult, Mental Disorders, Brain Mapping, Female, Glutamine, Humans, Magnetic Resonance Imaging, Male, Magnetic Resonance Spectroscopy, Protons, Psychiatric Status Rating Scales, Risk, Temporal Lobe, Thalamus, Glutamic Acid, Young Adult
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