Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex.
Matti Gärtner, Anne Weigand, Marvin Sören Meiering, David Weigner, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian Beckmann, Maarten Mennes, Andreas Wunder, Simone Grimm
Translational Psychiatry June 18, 2024 DOI: 10.1038/s41398-024-02977-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, randomized, single dose, parallel-group study Peer reviewed |
|---|---|
| Sample size | 75 |
| Population | Healthy male and female participants |
| Interventions | Ketamine Placebo |
| Duration | Single dose, 24-hour follow-up |
| Topics | Esketamine Ketamine |
| Keywords | Psychopharmacology Mental health Brain research Mood disorders |
| Citations | 1 |
| Key points | Ketamine decreases activity in all three ACC subregions during administration, but lamotrigine attenuates this only in the ventral subregions, and trait negative emotionality is linked to subgenual ACC changes. |
Abstract
Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine's antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes. Furthermore, the assessment of trait negative emotionality holds promise to link findings in healthy participants to potential AD mechanisms of ketamine. In this double-blind, placebo-controlled, randomized, single dose, parallel-group study, we collected resting-state fMRI data before, during, and 24 h after ketamine administration in a sample of 75 healthy male and female participants who were randomly allocated to one of three treatment conditions (ketamine, ketamine with lamotrigine pre- treatment, placebo). Spontaneous brain activity was extracted from two ventral and one dorsal subregions of the ACC. Our results showed activity decreases during the administration of ketamine in all three ACC subregions. However, only in the ventral subregions of the ACC this effect was attenuated by lamotrigine. 24 h after administration, ACC activity returned to baseline levels, but group differences were observed between the lamotrigine and the ketamine group. Trait negative emotionality was closely linked to activity changes in the subgenual ACC after ketamine administration. These results contribute to an understanding of the functional significance of ketamine effects in different subregions of the ACC by combining an approach to modulate glutamate release with the assessment of multiple timepoints and associations with trait negative emotionality in healthy participants.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 3
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects. The International Journal of Neuropsychopharmacology February 4, 2025
- Esketamine alleviates the pain-depression dyad: insights from exploratory transcriptomic profiling and Wnt4-associated molecular alterations within the anterior cingulate cortex Frontiers in Pharmacology October 16, 2026
- Ketamine’s impact on rumination-related brain dynamics: insights from a randomized controlled fMRI trial Translational Psychiatry August 18, 2026
Cites 22
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Ketamine: a paradigm shift for depression research and treatment Neuron March 1, 2019
and 17 more in the library