Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission from Depression
Vasileia Kotoula, Argyris Stringaris, Nuria Mackes, Ndabezinhle Mazibuko, Peter C. T. Hawkins, Maura L. Furey, Helen Valerie Curran, Mitul A. Mehta
medRxiv Preprint Server December 7, 2020 preprint DOI: 10.1101/2020.12.07.20230151 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial |
|---|---|
| Sample size | 37 |
| Population | Remitted depression patients free from symptoms and antidepressant treatments |
| Intervention | Ketamine |
| Duration | 2h post-infusion |
| Topics | Depression Ketamine Esketamine |
| Keywords | Rapid antidepressant Drug Medication Reward system Brain reward circuit Positive feedback Nucleus accumbens Ventral tegmental area Anhedonia Mental health Mood disorder Brain research Neurobiology Psychopharmacology |
| Citations | 9 |
| Key findings | Ketamine produced detectable changes in reward-related brain areas, particularly the nucleus accumbens and putamen, two hours after infusion, independent of symptom changes. |
Abstract
Ketamine as an antidepressant improves anhedonia, a pernicious symptom of depression as early as 2h post-infusion. The effects of ketamine on anhedonia are thought to be exerted via actions on reward-related brain areas—yet, these actions remain largely unknown. This study examines 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. In order to identify brain areas that are modulated by the drug per se and are not linked to symptom changes, we have recruited 37 participants who remitted from depression and were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned while performing a monetary reward task and we examined ketamine’s effects on pre-defined brain areas that are part of the reward circuit. An overall effect of ketamine 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, upon the receipt of smaller rewards and the levels of (2R,6R)-HNK, 2h post-infusion, significantly correlated with the activation observed in the ventral tegmental area (VTA) for that contrast. 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.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.