Emotional Processing And Brain Metabolism After Pharmacological Stimulation With Ketamine: Implications For Major Depression

Background / Purpose: Ketamine is a potent glutamatergic NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses, thus providing a valuable research tool for the investigation of the neurobiology of major depressive disorder (MDD). This multimodal imaging study in 23 healthy subjects reveals the neuropharmacological effects of a single intravenous subanaesthetic ketamine infusion on fMRI-BOLD responses during an emotional processing task and their relationship to glutamatergic metabolite concentrations in the pregenual anterior cingulate cortex (PACC) assessed by proton magnetic resonance spectroscopy (1H-MRS). Main conclusion: Our findings show that ketamine has the potential to increase negative BOLD responses (NBRs) in PACC, which have been found to be decreased in MDD patients during an emotional processing task. A correlation between glutamate/glutamine ratios as a putative spectroscopic marker of glutamatergic neurotransmission and task associated NBRs could be found after ketamine administration compared to baseline. Our multimodal findings suggest that the increased NBRs observed during ketamine infusion are most likely interpreted in terms of an increased baseline brain metabolism due to an increase in the glutamate-glutamine-cycling rate. Hence, the antidepressant effect of ketamine might be linked to a beneficial short-term influence on glutamatergic neurotransmission and cerebral neuroenergetics. Next steps: The same research protocol will be applied for MDD patients