Glutamate and Psychosis Risk
Abstract
Increasing evidence suggests that abnormalities in glutamatergic transmission may be associated with psychosis risk. Genetic polymorphisms associated with schizophrenia converge on NMDA receptor signalling pathways, and transgenic animal models and human neuroimaging studies have shown the functional impact of these risk alleles. Animal models have also shown that environmental risk factors, such as stress, cannabis use and maternal infection can result in glutamatergic dysfunction, and in vivo magnetic resonance spectroscopy (MRS) studies have detected glutamatergic abnormalities in individuals at clinical or genetic risk of psychosis. Glutamatergic dysfunction may impact on dopaminergic transmission, and ultimately lead to the emergence of psychosis. In this review, the evidence that genetic and environmental risk factors for psychosis impact on glutamatergic transmission is discussed. If glutamatergic abnormalities are present early in the disorder, this suggests that glutamatergic therapies may be useful in psychosis prevention.
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Biochemical, imaging, and electrophysiological measurements may help segregating patients into higher- and lower-risk groups.
“In addition, biochemical 140,141 , imaging 52,142,143 , and electrophysiological measurements 144 may help segregating patients into higher- and lower-risk groups.”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [142]
Cites
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Berridge, K. C., & Robinson, T. E. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00019-8 · Cited by 4,127 · see citing works
Kapur, S. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.1.13 · Cited by 2,813 · see citing works
Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vöckler, J., Dikranian, K., Tenkova, T. I., Stefovska, V., Turski, L., & Olney, J. W. (1999) · Science · doi:10.1126/science.283.5398.70 · Cited by 2,055 · see citing works
Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020 · see citing works
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Lisman, J. E., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.002 · Cited by 1,983 · see citing works
Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2569 · Cited by 1,154 · cited 2× · see citing works
“Modern in vivo neuroimaging studies in schizophrenia have now shown elevated synthesis and storage of presynaptic dopamine [41-48], amphetamine-stimulated dopamine release [49-51], and baseline occupancy of D2/3 receptors by dopamine [52, 53] in the striatum, and that around 60% occupancy of striatal D2 receptors is r…”
BackgroundFloresco, S. B., West, A. R., Ash, B., Moore, H., & Grace, A. A. (2003) · Nature Neuroscience · doi:10.1038/nn1103 · Cited by 1,106 · see citing works
Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring
Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00297.2003 · Cited by 1,025 · see citing works
Cortico-Basal Ganglia Reward Network: Microcircuitry
Sesack, S. R., & Grace, A. A. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.93 · Cited by 985 · see citing works
Amminger, G. P., Schäfer, M. R., Papageorgiou, K., Klier, C. M., Cotton, S. M., Harrigan, S. M., Mackinnon, A., McGorry, P. D., & Berger, G. E. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.192 · Cited by 896 · see citing works
Seeman, P., & Lee, T. (1975) · Science · doi:10.1126/science.1145194 · Cited by 869 · see citing works
Immune involvement in schizophrenia and autism: Etiology, pathology and animal models
Patterson, P. H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.016 · Cited by 766 · see citing works
Morrison, A. P., French, P., Walford, L., Lewis, S. W., Kilcommons, A., Green, J., Parker, S., & Bentall, R. P. (2004) · British Journal of Psychiatry · doi:10.1192/bjp.185.4.291 · Cited by 740 · see citing works
Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia
Meyer-Lindenberg, A., Miletich, R. S., Kohn, P. D., Esposito, G., Carson, R. E., Quarantelli, M., Weinberger, D. R., & Berman, K. F. (2002) · Nature Neuroscience · doi:10.1038/nn804 · Cited by 652 · see citing works
Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior
Goto, Y., & Grace, A. A. (2005) · Nature Neuroscience · doi:10.1038/nn1471 · Cited by 576 · see citing works
Increased Synaptic Dopamine Function in Associative Regions of the Striatum in Schizophrenia
Kegeles, L. S., Abi-Dargham, A., Frankle, W. G., Gil, R., Cooper, T. B., Slifstein, M., Hwang, D.-R., Huang, Y., Haber, S. N., & Laruelle, M. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.10 · Cited by 565 · see citing works
McGlashan, T. H., Zipursky, R. B., Perkins, D., Addington, J., Miller, T., Woods, S. W., A. Hawkins, K., E. Hoffman, R., Preda, A., Epstein, I., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.5.790 · Cited by 556 · see citing works
Cannon, T. D., Hennah, W., van Erp, T. G. M., Thompson, P. M., Lonnqvist, J., Huttunen, M., Gasperoni, T., Tuulio-Henriksson, A., Pirkola, T., Toga, A. W., et al. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1205 · Cited by 337 · see citing works
Howes, O., Bose, S., Turkheimer, F., Valli, I., Egerton, A., Stahl, D., Valmaggia, L., Allen, P., Murray, R., & McGuire, P. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.20 · Cited by 292 · see citing works
Self-citationFirst in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients
Pilowsky, L. S., Bressan, R. A., Stone, J. M., Erlandsson, K., Mulligan, R. S., Krystal, J. H., & Ell, P. J. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001751 · Cited by 278 · see citing works
Self-citationLife Events and Psychosis: Initial Results from the Camberwell Collaborative Psychosis Study
Bebbington, P., Wilkins, S., Jones, P., Foerster, A., Murray, R., Toone, B., & Lewis, S. (1993) · British Journal of Psychiatry · doi:10.1192/bjp.162.1.72 · Cited by 273 · see citing works
Hashimoto, K., Engberg, G., Shimizu, E., Nordin, C., Lindström, L. H., & Iyo, M. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.04.023 · Cited by 267 · see citing works
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. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.05.006 · Cited by 231 · see citing works
High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia
Heresco-Levy, U., Ermilov, M., Lichtenberg, P., Bar, G., & Javitt, D. C. (2004) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00707-8 · Cited by 222 · see citing works
Abi-Dargham, A., van de Giessen, E., Slifstein, M., Kegeles, L. S., & Laruelle, M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.12.007 · Cited by 213 · see citing works
Abdul-Monim, Z., Neill, J. C., & Reynolds, G. P. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107067097 · Cited by 206 · see citing works
Ruhrmann, S., Bechdolf, A., Kühn, K.-U., Wagner, M., Schultze-Lutter, F., Janssen, B., Maurer, K., Häfner, H., Gaebel, W., Möller, H.-J., et al. (2007) · British Journal of Psychiatry · doi:10.1192/bjp.191.51.s88 · Cited by 150 · see citing works
Cognitive impairment as a risk factor for psychosis
Reichenberg, A. (2005) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2005.7.1/areichenberg · Cited by 49 · see citing works
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Millan, M. J., Andrieux, A., Bartzokis, G., Cadenhead, K., Dazzan, P., Fusar-Poli, P., Gallinat, J., Giedd, J., Grayson, D. R., Heinrichs, M., et al. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.28 · Cited by 516 · see citing works
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Egerton, A., Chaddock, C. A., Winton-Brown, T. T., Bloomfield, M. A. P., Bhattacharyya, S., Allen, P., McGuire, P. K., & Howes, O. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.017 · Cited by 253 · see citing works
Self-citation
- Authors
- Egerton, A., Fusar-Poli, P., & M. Stone, J.
- Affiliations
- King's College London (GB)
- ORCID
- Egerton, Alice
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2012-02-01
- Volume
- 18
- Issue
- 4
- Pages
- 466-478
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2066451778
- Cited by
- 36
- References
- 28
- Citations by year
- 2025: 1 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 2
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (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 › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- glutamate, psychosis risk, schizophrenia, NMDA receptor signalling, glutamatergic dysfunction, genetic polymorphism, environmental risk factors, stress, cannabis use, maternal infection, magnetic resonance spectroscopy, dopamine signaling, psychosis prevention
- MeSH terms
- Animals, Disease Models, Animal, Humans, Psychotic Disorders, Risk Factors, Glutamic Acid, Genetic Predisposition to Disease
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