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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Dopamine / metabolism*
  • Glutamic Acid / metabolism*
  • Humans
  • Risk Factors
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*


  • Antipsychotic Agents
  • Glutamic Acid
  • Dopamine