This double-blind, randomized 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 of Right dorsolateral prefrontal cortex volumetric reduction is associated with antidepressant effect of low-dose ketamine infusion
“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.”
Authors: Wei-Chi Li, Li-Fen Chen, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Hui-Ju Wu, Shih-Jen Tsai, Ya-Mei Bai, Pei-Chi Tu & Mu-Hong Chen
Summary of Right dorsolateral prefrontal cortex volumetric reduction is associated with antidepressant effect of low-dose ketamine infusion
Low-dose ketamine infusion exerts fast-acting antidepressant and antisuicidal effects among patients with treatment-resistant depression. Still, the neuropathomechanisms underlying the rapid antidepressant and antisuicidal effects of low-dose ketamine remain uncertain.
The dorsolateral prefrontal cortex is one of the neuro-pathomechanisms of TRD. Patients with TRD have a reduced grey matter volume for their left DLPFC compared with the non-TRD and control groups.
Several neuroimaging studies have examined the functional changes in the brain induced by acute administration of ketamine, such as the increased activation of the bilateral prefrontal cortex and increased global signal regression values in the right lateral PFC. However, the changes in the GM volumes have received less attention. A study using whole-brain voxel-wise tensor-based morphometry found that the GM volume increased in the right inferior frontal cortex among 21 patients with TRD, but a study using GM volume in 28 healthy individuals found no significant effect of interaction or medication on GM volumes.
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https://doi.org/10.1016/j.jad.2023.05.024
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Cite this paper (APA)
Li, W. C., Chen, L. F., Su, T. P., Li, C. T., Lin, W. C., Wu, H. J., ... & Chen, M. H. (2023). 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. Journal of Affective Disorders, 335, 105-110.
Study details
Compounds studied
Ketamine
Topics studied
Depression
Treatment-Resistant Depression
Suicidality
Neuroscience
Study characteristics
Placebo-Controlled
Active Placebo
Double-Blind
Randomized
Participants
48
Humans
Compound Details
The psychedelics given at which dose and how many times
Ketamine 35 mg | 1x