@article{11f01dfa8aa449d3905b7d832b80dfae,
title = "Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission From Depression",
abstract = "Background: Ketamine as an antidepressant improves anhedonia as early as 2 hours after 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 predefined brain areas, namely, the dorsal and ventral striatum, ventral tegmental area, amygdala, and insula. We recruited 37 male and female participants with remitted depression who were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned 2 hours after drug administration in a double-blind crossover design (ketamine: 0.5 mg/kg and placebo) while performing a monetary reward task. Results: A significant main effect of ketamine was observed across all regions of interest 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 on the receipt of smaller rewards compared with neutral. The levels of (2R,6R)-hydroxynorketamine 2 hours after 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 2 hours after infusion, which occur without symptom changes and support the idea that ketamine might improve reward-related symptoms via modulation of response to feedback.",
keywords = "(2R,6R)-HNK, Feedback, Ketamine, Monetary incentive delay (MID), Reward-processing, VTA",
author = "Vasileia Kotoula and Argyris Stringaris and Nuria Mackes and Ndabezinhle Mazibuko and Hawkins, {Peter C.T.} and Maura Furey and Curran, {H. Valerie} and Mehta, {Mitul A.}",
note = "Funding Information: The research reported in this article was supported by grants from Johnson & Johnson awarded to University College London (HVC) and King{\textquoteright}s College London (Grant No. 23034 [to MAM, AS]). This paper represents independent research part-supported by a scholarship supported from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King{\textquoteright}s College London (to MAM, VK). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Funding Information: The research reported in this article was supported by grants from Johnson & Johnson awarded to University College London (HVC) and King's College London (Grant No. 23034 [to MAM, AS]). This paper represents independent research part-supported by a scholarship supported from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London (to MAM, VK). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. We would like to thank the Centre for Neuroimaging Sciences{\textquoteright} research staff for all their hard work and support throughout this research project. HVC's research is supported by the UK Medical Research Council and NIHR; she has consulted for Janssen on esketamine. MAM has received funding from Johnson & Johnson, Lundbeck, and Takeda and has acted as a consultant for Lundbeck and Takeda. MF is an employee of Janssen Research and Development. All other authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Ketamine's Actions on Rumination Mechanisms as an Antidepressant (KARMA); https://clinicaltrials.gov/ct2/show/NCT04656886; NCT04656886. Publisher Copyright: {\textcopyright} 2021 Society of Biological Psychiatry",
year = "2022",
month = mar,
doi = "10.1016/j.bpsc.2021.05.009",
language = "English",
volume = "7",
pages = "285--292",
journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",
issn = "2451-9022",
publisher = "Elsevier Inc.",
number = "3",
}