A preliminary study of the association of increased anterior cingulate gamma-aminobutyric acid with remission of depression after ketamine administration.

Gamma-aminobutyric acid (GABA) and glutamate neurotransmission have been implicated in the pathophysiology of depression and mechanistically linked to ketamine's antidepressant response. Seven patients with treatment-resistant depression enrolled in an open-label, feasibility trial of a single IV 40-min ketamine infusion during a functional MR spectroscopy (fMRS) scan utilizing a novel frequency adjusting MEGA-PRESS sequence. Next-day treatment remission and reduction in the MADRS scores correlated with anterior cingulate cortex peak GABA levels. These novel findings provide further insights into the underlying neurobiological mechanisms of ketamine and, if confirmed in larger studies, would be encouraging for further development of GABAergic biomarker associated with ketamine response.