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Hum Brain Mapp. 2016 Mar;37(3):1080-90. doi: 10.1002/hbm.23085. Epub 2016 Jan 29.

The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study.

Li CT1,2, Chen MH1,2, Lin WC1,2, Hong CJ1,2, Yang BH3, Liu RS3, Tu PC1,2, Su TP1,2,4.

Author information

1
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
2
Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
3
Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
4
Institute of Brain Science, National Yang-Ming University, Taipei, 112, Taiwan.

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 (18) F-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 (18) F-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.

KEYWORDS:

glucose; ketamine; prefrontal cortex; treatment-resistant depression

PMID:
26821769
DOI:
10.1002/hbm.23085
[Indexed for MEDLINE]

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