Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study

Biol Psychiatry. 2000 Feb 15;47(4):305-13. doi: 10.1016/s0006-3223(99)00159-6.


Background: Functional imaging studies suggest a specific role of the anterior brain regions in the pathogenesis of major depression. The aim of this study was to evaluate possible neurochemical alterations in the frontomesial cortex in patients with major depressive episode using in vivo proton magnetic resonance spectroscopy ((1)H-MRS).

Methods: Single voxel (1)H-MRS was performed in 19 patients with major depressive episodes and 18 age-matched healthy controls within the anterior cingulate cortex and the parietal white matter. Absolute concentrations were estimated for N-acetyl-aspartate, choline-containing compounds, total creatine, myo-inositol, unresolved glutamate and glutamine (Glx) and glutamate alone (Glu). Voxel composition was analyzed by image segmentation into cerebrospinal fluid (CSF), grey and white matter.

Results: MANOVA test for Glx and Glu using age, percent CSF and percent grey matter contribution as covariates yielded a significant group effect within the anterior cingulate due to decrease of Glx in patients (-10.4%, p =.013). Considering only severely depressed patients, both Glx and Glu (-14.3%, p =.03) showed a significant decrease. There was no significant group effect for the neuronal marker NAA, creatine, choline or myo-inositol in either localization.

Conclusions: This study suggests a possible role of altered glutamatergic neurotransmission within the anterior cingulate in the pathogenesis of mood disorders. The otherwise unremarkable findings of major brain metabolites confirms lack of neurodegenerative or membrane metabolic changes in major depression.

MeSH terms

  • Adult
  • Aged
  • Aspartic Acid / metabolism
  • Choline / metabolism
  • Creatine / metabolism
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / metabolism*
  • Female
  • Frontal Lobe / metabolism*
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism
  • Gyrus Cinguli / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Myo-Inositol-1-Phosphate Synthase / metabolism
  • Severity of Illness Index


  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • Myo-Inositol-1-Phosphate Synthase
  • Creatine
  • Choline