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Review
. 2015 Feb;29(2):97-115.
doi: 10.1177/0269881114563634. Epub 2015 Jan 13.

Glutamate and dopamine in schizophrenia: an update for the 21st century

Oliver Howes  1 , Rob McCutcheon  2 , James Stone  2
Affiliations
Review

Glutamate and dopamine in schizophrenia: an update for the 21st century

Oliver Howes et al. J Psychopharmacol. 2015 Feb.

Abstract

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.

Keywords: D2; MR; NMDA; PET; Schizophrenia; aetiology; antipsychotic; dopamine; glutamate; imaging; mechanisms; psychosis; treatment.

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Conflict of interest statement

Declaration of interest: Declaration of interest: ODH and JMS have been on the speaker bureau or have received investigator-initiated grant support from a number of companies with an interest in antipsychotic drugs (AZ, BMS, Eli Lilly, Jansenn, Leyden-Delta, Lundbeck, Roche, Servier). This study was funded by a Medical Research Council (UK) grant to Dr Howes (grant number: MC-A656-5QD30) and the National Institute of Health Research Biomedical Research Council grant to King’s College London

Figures

Figure 1
Figure 1
Interactions between glutamatergic and dopaminergic pathways
See this image and copyright information in PMC

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