Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments

J. H. Krystal, G. Sanacora, H. Blumberg, A. Anand, D. S. Charney, G. Marek, C. N. Epperson, A. Goddard, G. F. Mason

Research output: Contribution to journalArticlepeer-review

484 Scopus citations


Glutamate and γ-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.

Original languageEnglish
Pages (from-to)S71-S80
JournalMolecular Psychiatry
StatePublished - 2002
Externally publishedYes


  • Anticonvulsant
  • Bipolar disorder
  • Depression
  • Magnetic resonance spectroscopy
  • Metabotropic glutamate receptor
  • N-methyl-D-aspartate (NMDA)
  • Panic disorder
  • Premenstrual dysphoric disorder
  • Serotonin-2A receptor
  • Voltage-gated calcium channel


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