Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission from Depression
This double-blind, placebo-controlled study (n=37) found that ketamine improved responses to rewards two hours after depressed patients had received ketamine (35mg/70kg) treatment. This correlated with neurological observations (increases in activation of NAc, the putamen, the insula, and the caudate).
Authors
- Valerie Curran
- Mitul Mehta
Published
Abstract
Background
Ketamine as an antidepressant improves anhedonia as early as 2h post-infusion. These drug effects are thought to be exerted via actions on reward-related brain areas-yet, these actions remain largely unknown. Our study investigates ketamine’s effects during the anticipation and receipt of an expected reward, after the psychotomimetic effects of ketamine have passed, when early antidepressant effects are reported.
Methods
We examined ketamine’s effects during the anticipation and receipt of expected rewards on pre-defined brain areas, namely the dorsal and ventral striatum, the ventral tegmental area, the amygdala and the insula. We have recruited 37 male and female participants who remitted from depression and were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned, 2h after drug administration, in a double-blind cross over design (ketamine:0.5mg/kg and placebo) while performing a monetary reward task.
Results
A significant main effect of ketamine, across all ROIs, was observed during the anticipation and feedback phases of win and no-win trials. The drug effects were particularly prominent in the nucleus accumbens and putamen, which showed increased activation upon the receipt of smaller rewards compared to neutral. The levels of (2R,6R)-HNK, 2h post-infusion, significantly correlated with the activation observed in the ventral tegmental area for that contrast.
Conclusions
These findings demonstrate that ketamine can produce detectable changes in reward-related brain areas, 2h after infusion, which occur without symptom changes and support the idea that ketamine might improve reward-related symptoms via modulation of response to feedback.
Research Summary of 'Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission from Depression'
Introduction
Major depressive disorder is associated with altered reward processing and persistent anhedonia, deficits that can remain during remission and predict onset. Earlier work shows that ketamine produces rapid antidepressant and anti-anhedonic effects detectable as early as 2 hours after infusion, but it is unclear whether these behavioural effects reflect direct engagement of reward-processing circuitry or are secondary to symptom improvement. Neuroimaging studies have implicated striatal, insular and prefrontal nodes of the mesocorticolimbic pathway in reward anticipation and feedback, and prior PET and fMRI reports have linked early post-ketamine metabolic and activation changes in such regions to symptom change, yet the temporal and mechanistic relationships remain unsettled. Kotoula and colleagues set out to test whether a single subanaesthetic ketamine infusion (0.5 mg/kg) modulates neural responses to reward anticipation and feedback independently of concurrent symptom change. They applied a well-validated monetary incentive delay (MID) task and a pre-defined set of regions of interest (ventral and dorsal striatum, ventral tegmental area (VTA), amygdala, insula, plus an exploratory sgACC analysis), scanning participants 2 hours after infusion in a double-blind crossover design. The investigators also measured plasma concentrations of ketamine and main metabolites, including (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), to explore relationships between metabolite exposure and task-related brain activity.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Kotoula, V., Stringaris, A., Mackes, N., Mazibuko, N., Hawkins, P. C., Furey, M., Curran, H. V., & Mehta, M. A. (2022). Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission from Depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 7(3), 285-292. https://doi.org/10.1016/j.bpsc.2021.05.009
References (4)
Papers cited by this study that are also in Blossom
Nutt, D. J. · Journal of Psychopharmacology (2015)
Zanos, P., Moaddel, P. J., Morris, P. J. et al. · Nature (2016)
Murrough, J. W., Perez, A. M., Pillemer, S. et al. · Biological Psychiatry (2012)
Abdallah, C. G., Averill, L. A., Collins, K. A. et al. · Neuropsychopharmacology (2016)
Cited By (1)
Papers in Blossom that reference this study
Keeler, J. L., Treasure, J., Juruena, M. F. et al. · Nutrients (2021)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.