Effects of an antidepressant dose of Ketamine on prefrontal aspartate, glutamine and Gaba levels in healthy subjects: Assessing the post-infusion interval with 1H-MRS

Objective Using proton magnetic resonance spectroscopy (1H-MRS) an increase in glutamatergic metabolites has been previously observed during ketamine challenge (Stone 2012, Rowland 2005). Preclinical evidence indicates that this effect may be associated with the rapid antidepressant action of ketamine (Duman 2012). Hence, we aimed at investigating the neurometabolic changes in the 3-4 hour post-infusion interval when the antidepressant effect usually starts to build up (aan het Rot 2012). Method 13 age- and sex-matched healthy subjects completed two separate 1H-MRS sessions. Approximately 210 minutes before, either placebo or S-ketamine (i.v. bolus of 0.12 mg/kg, infusion of 0.25 mg/kg/h over 40 min) was administered in a double-blind randomized manner. Single voxel 1H-MRS spectra were acquired from a volume of interest in the pregenual anterior cingulate cortex. Results We found a significant increase in prefrontal glutamine concentrations as well as a significant decrease in aspartate concentrations, a trend-level increase in the glutamine- to-glutamate ratio as well as a decrease in GABA concentrations after ketamine administration compared to placebo. Conclusion Since reduced glutamine levels were found in depressed patients with high levels of anhedonia (Walter 2009), the observed shift in the excitatory-inhibitory balance in the PACC following ketamine administration may play an important role in restoring parts of the disrupted neurometabolic homeostasis in depression