Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants
This double-blind, placebo-controlled study (n=57) investigated ketamine’s effects on brain activity (BOLD) during an emotional processing task where fMRI of participants with depression (MDD) showed greater activity than healthy participants. After ketamine treatment, the depressed participants showed similar levels of brain activity, suggesting a normalization of function during emotional processing.
Authors
- Carlos Zarate
- John Evans
- Allison Nugent
Published
Abstract
Background
In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine’s effects on brain function in major depressive disorder (MDD). This study examined ketamine’s effects on functional magnetic resonance imaging activity during an emotional processing task.
Methods
A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level-dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors.
Results
A group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions.
Conclusions
The main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine’s actions in the brain.
Research Summary of 'Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants'
Introduction
Reed and colleagues place this study in the context of an urgent need for faster-acting, more effective treatments for major depressive disorder (MDD). Previous neuroimaging work has documented differences between people with MDD and healthy controls (HCs) during emotional processing, including altered anterior cingulate cortex (ACC) and prefrontal activation and a bias toward negative stimuli. Traditional antidepressants tend to ‘‘normalise’’ under- or overactivation in some regions, but ketamine, a glutamatergic modulator with rapid antidepressant effects, has been less well characterised in emotional processing tasks; prior studies of ketamine either lacked placebo controls or did not include both clinical and healthy samples. This study set out to examine how ketamine affects blood oxygen level-dependent (BOLD) activity during an emotional face-processing task in both treatment-resistant MDD participants and HCs using a double-blind, placebo-controlled crossover design. The investigators hypothesised that ketamine would differentially alter BOLD activity in MDD versus HCs, tending to decrease activation in MDD and shift their activity patterns toward those of HCs after placebo (a ‘‘normalisation’’), with task condition (explicit versus implicit processing) modulating these effects.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Reed, J. L., Nugent, A. C., Furey, M. L., Szczepanik, J. E., Evans, J. W., & Zarate, C. A. (2019). Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(7), 610-618. https://doi.org/10.1016/j.bpsc.2019.01.005
References (5)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Murrough, J. W., Collins, K. A., Fields, J. et al. · Translational Psychiatry (2015)
Reed, L. J., Nugent, A. C., Furey, M. et al. · NeuroImage (2018)
Nugent, A. C., Ballard, E. D., Gould, T. D. et al. · Molecular Psychiatry (2018)
Cited By (4)
Papers in Blossom that reference this study
Hack, L. M., Zhang, X., Heifets, B. D. et al. · Nature Communications (2023)
Zavaliangos-Petropulu, A., Mcclintock, S. M., Khalil, J. et al. · Journal of Affective Disorders (2023)
Norbury, A., Rutter, S. B., Collins, A. B. et al. · Neuropsychopharmacology (2021)
Van Hedger, K., Mayo, L. M., Bershad, A. K. et al. · Current Addiction Reports (2021)
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