Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations

Eur Neuropsychopharmacol. 2015 Aug;25(8):1109-17. doi: 10.1016/j.euroneuro.2015.04.016. Epub 2015 May 1.


Proton magnetic resonance spectroscopy ((1)H MRS) measures glutamatergic metabolites namely glutamate and glutamine located in neurons and astrocytes respectively. In this meta-analysis the contribution of glutamatergic neurotransmission to depressive symptoms was evaluated together with other putative prefrontal metabolites described in the pathogenesis of mood disorders, and in relation to treatment effects. A comprehensive literature search up to 2014 identified 17 reports which measured absolute concentrations of neurometabolites in the prefrontal cortex with (1)H MRS meeting criteria for inclusion in this meta-analysis. Excess of heterogeneity was investigated with meta-regressions. The analyses showed an exclusive reduction in absolute values of the composite measure of Glutamine and Glutamate (Glx) in the prefrontal cortex in depression, correlating in meta-regression analyses with treatment severity. Glutamate measurements in isolation did not differ vs. healthy controls or in relation to treatment and/or clinical improvement. Similarly there were no significant changes in other neurometabolites at baseline and following treatment. The analysis supports a role for glutamatergic dysfunction in the pathogeneses of mood dysregulation. The reduction in the absolute Glx values in the absence of changes in glutamate levels, suggests a possible modulatory role of astrocytes in the pathophysiology of depression.

Keywords: Affective disorders; Depression; Glutamate; MRS; Magnetic resonance spectroscopy; Meta-analysis.

Publication types

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

MeSH terms

  • Affect / physiology*
  • Depressive Disorder / metabolism*
  • Glutamic Acid / metabolism*
  • Humans
  • Prefrontal Cortex / metabolism*


  • Glutamic Acid