Cross-sectional Study of Glutamate in the Anterior Cingulate and Hippocampus in Schizophrenia

Schizophr Bull. 2016 Mar;42(2):425-33. doi: 10.1093/schbul/sbv124. Epub 2015 Sep 2.


Background: There has been growing support for dysfunctions of the excitatory glutamatergic system and its implications for the psychophysiology of schizophrenia. However, previous studies reported mixed results regarding glutamate concentrations in schizophrenia with varying deviations across brain regions.

Methods: We used an optimized proton magnetic resonance spectroscopy procedure to measure absolute glutamate concentrations in the left hippocampal region and the anterior cingulate cortex (ACC) in 29 medicated patients with schizophrenia and in 29 control participants without mental disorder.

Results: The glutamate concentrations were significantly lower in the ACC but higher in the hippocampus of patients compared to controls. ACC and hippocampal glutamate concentrations correlated positively in patients but not in controls. ACC glutamate was weakly associated with Clinical Global Impression score and duration of illness in patients.

Conclusion: Glutamate concentrations in schizophrenia deviate from controls and show associations with disease severity. A higher concentration of hippocampal glutamate in schizophrenia compared to controls is shown. The association between ACC and hippocampus glutamate concentrations in patients with schizophrenia suggests an abnormal coupling of excitatory systems compared to controls as predicted by previous glutamate models of schizophrenia.

Keywords: MR spectroscopy; anterior cingulated; glutamate; glutamatergic hypothesis of schizophrenia; hippocampus; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Female
  • Glutamic Acid / metabolism*
  • Gyrus Cinguli / metabolism*
  • Hippocampus / metabolism*
  • Humans
  • Male
  • Proton Magnetic Resonance Spectroscopy
  • Schizophrenia / metabolism*
  • Severity of Illness Index*


  • Glutamic Acid