Glutamate and GABA Homeostasis and Neurometabolism in Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is a leading cause of distress, disability, and suicides. As per the latest WHO report, MDD affects more than 260 million people worldwide. Despite decades of research, the underlying etiology of depression is not fully understood. Glutamate and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters, respectively, in the matured central nervous system. Imbalance in the levels of these neurotransmitters has been implicated in different neurological and psychiatric disorders including MDD. ¹H nuclear magnetic resonance (NMR) spectroscopy is a powerful non-invasive method to study neurometabolites homeostasis in vivo. Additionally, ¹³C-NMR spectroscopy together with an intravenous administration of non-radioactive ¹³C-labeled glucose or acetate provides a measure of neural functions. In this review, we provide an overview of NMR-based measurements of glutamate and GABA homeostasis, neurometabolic activity, and neurotransmitter cycling in MDD. Finally, we highlight the impact of recent advancements in treatment strategies against a depressive disorder that target glutamate and GABA pathways in the brain.

Keywords: 13C-NMR spectroscopy; antidepressant; brain; glutamine; ketamine; neurocircuitry; neurometabolism; neurotransmitter.