Glutamate and dopamine in schizophrenia: An update for the 21 st century
Open accessAbstract
The glutamate and dopamine hypotheses are leading theories of the pathoaetiology of schizophrenia. Both were initially based on indirect evidence from pharmacological studies supported by post-mortem findings, but have since been substantially advanced by new lines of evidence from in vivo imaging studies. This review provides an update on the latest findings on dopamine and glutamate abnormalities in schizophrenia, focusing on in vivo neuroimaging studies in patients and clinical high-risk groups, and considers their implications for understanding the biology and treatment of schizophrenia. These findings have refined both the dopamine and glutamate hypotheses, enabling greater anatomical and functional specificity, and have been complemented by preclinical evidence showing how the risk factors for schizophrenia impact on the dopamine and glutamate systems. The implications of this new evidence for understanding the development and treatment of schizophrenia are considered, and the gaps in current knowledge highlighted. Finally, the evidence for an integrated model of the interactions between the glutamate and dopamine systems is reviewed, and future directions discussed.
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Proton MRS studies revealed hyperglutamatergic activity in patients with schizophrenia and groups at high risk of developing schizophrenia, which may be attributable to NMDAR hypofunction.
“Proton magnetic resonance spectroscopy (MRS studies) revealed hyperglutamatergic activity in patients with schizophrenia and groups at high risk of developing schizophrenia, which may be attributable to NMDAR hypofunction 20 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [20]
An NMDAR SPECT study pointed to lower NMDAR activity in unmedicated patients with schizophrenia, although this finding awaits confirmation with newer, more specific probes.
“An NMDAR single-photon emission computed tomography (SPECT) study pointed to lower NMDAR activity in unmedicated patients with schizophrenia 19 , although this finding awaits confirmation with newer, more specific probes 20 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [20]
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References 270 · Cited by 702
- Authors
- Howes, O., McCutcheon, R., & Stone, J.
- Affiliations
- King's College London (GB)
- Psychiatric Imaging, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK
- Corresponding author
- Howes, Oliver
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2015-01-13
- Volume
- 29
- Issue
- 2
- Pages
- 97-115
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- PMC
- PMC4902122
- OpenAlex
- W2082642969
- Cited by
- 702
- References
- 270
- Citations by year
- 2026: 32 · 2025: 40 · 2024: 40 · 2023: 60 · 2022: 82 · 2021: 72 · 2020: 102 · 2019: 89 · 2018: 66 · 2017: 50 · 2016: 39 · 2015: 29
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2014-17-008)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, glutamate hypothesis, dopamine hypothesis, dopamine-glutamate interaction, in vivo brain imaging, schizophrenia pathophysiology, schizophrenia treatment, glutamatergic system, dopaminergic system
- MeSH terms
- Animals, Dopamine, Humans, Risk Factors, Schizophrenia, Antipsychotic Agents, Glutamic Acid
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