Right dorsolateral prefrontal cortex volumetric reduction is associated with antidepressant effect of low-dose ketamine infusion: A randomized, double-blind, midazolam-controlled PET-MRI clinical trial
Bai, Y. M., Chen, L-F., Chen, M. H., Li, C. T., Li, W., Su, T. P., Tsai, S-J., Tu, P. C., Wu, H-J.
This double-blind, randomised study (n=48) involving patients with treatment-resistant depression (TRD) and suicidal ideation (SI) evaluated the effects of a single infusion of 35mg/70kg ketamine or 3.15mg/70kg midazolam. Using positron emission tomography-magnetic resonance imaging, the study observed a small but significant volumetric reduction in the right dorsolateral prefrontal cortex (DLPFC) in the ketamine group compared to the midazolam group, and a greater reduction in depressive symptoms was associated with smaller decreases in right DLPFC volumes.
Abstract
Background Evidence has shown a rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression (TRD) and prominent suicidal ideation (SI). The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the TRD pathomechanisms.Objective Whether the structural and functional changes of the DLPFC, particularly Brodmann area 46, are associated with the antidepressant and antisuicidal effects of ketamine infusion among such patients is unknown.Methods We randomized 48 patients with TRD and SI into groups receiving a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale were used to assess symptoms. Positron emission tomography (PET)-magnetic resonance imaging was conducted prior to infusion and on Day 3 postinfusion. We performed longitudinal voxel-based morphometry (VBM) analysis to evaluate the gray matter (GM) volume changes of the DLPFC. The standardized uptake value ratio (SUVr) of 18F-fluorodeoxyglucose PET images was calculated using the SUV of the cerebellum as a reference region.Results The VBM analysis revealed a small but significant volumetric reduction in the right DLPFC in the ketamine group compared with that in the midazolam group. A greater reduction in depressive symptoms was associated with a smaller decrease in right DLPFC volumes (p = 0.025). However, we found no SUVr changes of the DLPFC between baseline and post-Day 3 ketamine infusion.Discussion The optimal modulation of the right DLPFC GM volumes may play an essential role in the antidepressant neuromechanisms of low-dose ketamine.