Low-dose ketamine has been found to have robust and rapid antidepressant effects. A hypoactive prefrontal cortex (PFC) and a hyperactive amygdala have been suggested to be associated with treatment-resistant depression (TRD). However, it is unclear whether the rapid antidepressant mechanisms of ketamine on TRD involve changes in glutamatergic neurotransmission in the PFC and the amygdala.Methods:
A group of 48 TRD patients were recruited and equally randomized into three groups (A: 0.5 kg/mg-ketamine; B: 0.2 kg/mg-ketamine; and C: normal saline [NS]). Standardized uptake values (SUV) of glucose metabolism measured by 18F-FDG positron-emission-tomography before and immediately after a 40-min ketamine or NS infusion were used for subsequent region-of-interest (ROI) analyses (a priori regions: PFC and amygdala) and whole-brain voxel-wise analyses and were correlated with antidepressant responses, as defined by the Hamilton depression rating scale score. The 18F-FDG signals were used as a proxy measure of glutamate neurotransmission.Results:
The ROI analysis indicated that Group A and Group B, but not Group C, had increases in the SUV of the PFC (group-by-time interaction: F = 7.373, P = 0.002), whereas decreases in the SUV of the amygdala were observed in all three groups (main effect of time, P < 0.001). The voxel-wise analysis further confirmed a significant group effect on the PFC (corrected for family-wise errors, P < 0.05; post hoc analysis: Group A Ketamine's rapid antidepressant effects involved the facilitation of glutamatergic neurotransmission in the PFC. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
Ketamine's rapid antidepressant effects involved the facilitation of glutamatergic neurotransmission in the PFC. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.