Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine

Marc S. Lener, Mark J. Niciu, Elizabeth D. Ballard, Minkyung Park, Lawrence T. Park, Allison C. Nugent, Carlos A. Zarate

Research output: Contribution to journalReview articlepeer-review

285 Scopus citations

Abstract

In patients with major depressive disorder or bipolar disorder, abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate and gamma-aminobutyric acid have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic-dose ketamine has led to a collection of studies that have examined neurochemical (e.g., glutamatergic and gamma-aminobutyric acidergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation.

Original languageEnglish (US)
Pages (from-to)886-897
Number of pages12
JournalBiological Psychiatry
Volume81
Issue number10
DOIs
StatePublished - May 15 2017

Keywords

  • Bipolar disorder
  • Glutamate
  • Ketamine
  • Major depressive disorder
  • Mood disorder
  • NMDA receptor antagonist

ASJC Scopus subject areas

  • Biological Psychiatry

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