The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study
This double-blind placebo-controlled study (n=48) investigated the antidepressant efficacy of ketamine (14 or 35mg/70kg) in patients with depression and found evidence that its rapid antidepressant effects at 40 and 240 minutes post-treatment were facilitated by glutamatergic neurotransmission in the prefrontal cortex.
Authors
- Tung-Ping Su
- Mu-Hong Chen
Published
Abstract
Background
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<Group C, Group B<Group C). The SUV differences in the PFC predicted the antidepressant responses at 40 and 240 min post-treatment. The PFC changes did not differ between those with and without side effects.
Conclusion
Ketamine's rapid antidepressant effects involved the facilitation of glutamatergic neurotransmission in the PFC.
Research Summary of 'The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study'
Introduction
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant effects at low doses and acts directly on the glutamatergic system. Prior work has suggested that treatment-resistant depression (TRD) is characterised by hypoactivity in the prefrontal cortex (PFC) alongside hyperactivity in limbic regions such as the amygdala, but it is unclear whether ketamine's rapid clinical benefits in TRD involve changes in glutamatergic neurotransmission specifically within these regions. Li and colleagues designed a randomized, double-blind, placebo-controlled study using 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) to probe rapid changes in brain glucose uptake as a proxy for glutamate-related activity. The primary hypothesis was that low-dose ketamine would rapidly increase PFC activity; the amygdala was also examined as a key limbic node in mood circuitry. Scans and clinical ratings were scheduled to capture effects within the first hour after infusion and to relate imaging changes to fast antidepressant responses.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Li, C., Chen, M., Lin, W., Hong, C., Yang, B., Liu, R., Tu, P., & Su, T. (2016). The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study. Human Brain Mapping, 37(3), 1080-1090. https://doi.org/10.1002/hbm.23085
References (4)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Lally, N., Nugent, A. C., Luckenbaugh, D. A. et al. · Translational Psychiatry (2014)
Nutt, D. J. · Journal of Psychopharmacology (2015)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Cited By (7)
Papers in Blossom that reference this study
Matsingos, A., Wilhelm, M., Noor, L. et al. · Frontiers in Psychiatry (2024)
Li, W. C., Chen, L. F., Su, T. P. et al. · Journal of Affective Disorders (2023)
Muthukumaraswamy, S., Forsyth, B., Lumley, T. · Expert Review of Clinical Pharmacology (2021)
Bahji, A., Vazquez, G. H., Zarate, C. A. · Journal of Affective Disorders (2021)
Kohtala, S., Alitalo, O., Rosenholm, M. et al. · Pharmacology and Therapeutics (2020)
Su, T. P., Chen, M. H., Li, C. T. et al. · Neuropsychopharmacology (2017)
Lener, M. S., Niciu, M. J., Ballard, E. D. et al. · Biological Psychiatry (2017)
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