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PMID: 25586400 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

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

Journal of psychopharmacology (Oxford, England) ·Vol. 29 ·No. 2 ·2015-02-00 ·Pages 97-115

Howes O, McCutcheon R, Stone J

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
MeSH Terms
Animals Antipsychotic Agents/pharmacology,therapeutic use Dopamine/metabolism Glutamic Acid/metabolism Humans Risk Factors Schizophrenia/drug therapy,metabolism
Chemicals
Antipsychotic Agents Glutamic Acid Dopamine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Howes Oliver
Psychiatric Imaging, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK Institute of Psychiatry, King's College London, London, UK oliver.howes@kcl.ac.uk.
McCutcheon Rob
Psychiatric Imaging, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK Institute of Psychiatry, King's College London, London, UK.
Stone James
Psychiatric Imaging, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK Institute of Psychiatry, King's College London, London, UK.
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Article Info
Journal
Journal of psychopharmacology (Oxford, England)
Abbr.
J Psychopharmacol
ISSN
1461-7285
DOI
10.1177/0269881114563634
Email
oliver.howes@kcl.ac.uk
Published
2015-02-00
Epub
2015-00-13
Pages
97-115
Language
English
Region
United States
NLM ID
8907828
PMCID
PMC4902122
Subset
IM
Grants
Medical Research Council · G0700995 · United Kingdom
Medical Research Council · MC_U120097115 · United Kingdom
Medical Research Council · MR/L003988/1 · United Kingdom
Medical Research Council · MC-A656-5QD30 · United Kingdom
External Links
PubMed source DOI: 10.1177/0269881114563634 PMC Full Text View journal details
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