Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study
Abstract Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine,...
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| Format: | Article |
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Nature Publishing Group
2024-10-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-024-03120-6 |
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| author | Marvin S. Meiering David Weigner Matti Gärtner Luisa Carstens Christian Keicher Rita Hertrampf Christian F. Beckmann Maarten Mennes Andreas Wunder Anne Weigand Simone Grimm |
| author_facet | Marvin S. Meiering David Weigner Matti Gärtner Luisa Carstens Christian Keicher Rita Hertrampf Christian F. Beckmann Maarten Mennes Andreas Wunder Anne Weigand Simone Grimm |
| author_sort | Marvin S. Meiering |
| collection | DOAJ |
| description | Abstract Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Examining the antagonistic effects of ketamine and lamotrigine on glutamate transmission holds promise to identify effects of ketamine that are mediated through changes in the glutamatergic system. Investigating this modulation in relation to both the acute and sustained effects of ketamine on functional activity and connectivity during negative emotional processing should therefore provide novel insights. 75 healthy subjects were investigated in a double-blind, single-dose, randomized, placebo-controlled, parallel-group study with three treatment conditions (ketamine, lamotrigine pre-treatment, placebo). Participants completed an emotional face viewing task during ketamine infusion and 24 h later. Acute ketamine administration decreased hippocampal and Default Mode Network (DMN) activity and increased fronto-limbic coupling during negative emotional processing. Furthermore, while lamotrigine abolished the ketamine-induced increase in functional connectivity, it had no acute effect on activity. Sustained (24 h later) effects of ketamine were only found for functional activity, with a significant reduction in the posterior DMN. This effect was blocked by pretreatment with lamotrigine. Our results suggest that both the acute increases in fronto-limbic coupling and the delayed decrease in posterior DMN activity, but not the attenuated limbic and DMN recruitment after ketamine, are mediated by altered glutamatergic transmission. |
| format | Article |
| id | doaj-art-9469d90c67df4aa4ada2f673bd2b081c |
| institution | OA Journals |
| issn | 2158-3188 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Publishing Group |
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| series | Translational Psychiatry |
| spelling | doaj-art-9469d90c67df4aa4ada2f673bd2b081c2025-08-20T02:20:38ZengNature Publishing GroupTranslational Psychiatry2158-31882024-10-0114111010.1038/s41398-024-03120-6Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI studyMarvin S. Meiering0David Weigner1Matti Gärtner2Luisa Carstens3Christian Keicher4Rita Hertrampf5Christian F. Beckmann6Maarten Mennes7Andreas Wunder8Anne Weigand9Simone Grimm10Medical School BerlinMedical School BerlinMedical School BerlinMedical School BerlinCharité Research Organisation GmbHCharité Research Organisation GmbHSBGneuro LtdSBGneuro LtdTranslational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KGMedical School BerlinMedical School BerlinAbstract Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Examining the antagonistic effects of ketamine and lamotrigine on glutamate transmission holds promise to identify effects of ketamine that are mediated through changes in the glutamatergic system. Investigating this modulation in relation to both the acute and sustained effects of ketamine on functional activity and connectivity during negative emotional processing should therefore provide novel insights. 75 healthy subjects were investigated in a double-blind, single-dose, randomized, placebo-controlled, parallel-group study with three treatment conditions (ketamine, lamotrigine pre-treatment, placebo). Participants completed an emotional face viewing task during ketamine infusion and 24 h later. Acute ketamine administration decreased hippocampal and Default Mode Network (DMN) activity and increased fronto-limbic coupling during negative emotional processing. Furthermore, while lamotrigine abolished the ketamine-induced increase in functional connectivity, it had no acute effect on activity. Sustained (24 h later) effects of ketamine were only found for functional activity, with a significant reduction in the posterior DMN. This effect was blocked by pretreatment with lamotrigine. Our results suggest that both the acute increases in fronto-limbic coupling and the delayed decrease in posterior DMN activity, but not the attenuated limbic and DMN recruitment after ketamine, are mediated by altered glutamatergic transmission.https://doi.org/10.1038/s41398-024-03120-6 |
| spellingShingle | Marvin S. Meiering David Weigner Matti Gärtner Luisa Carstens Christian Keicher Rita Hertrampf Christian F. Beckmann Maarten Mennes Andreas Wunder Anne Weigand Simone Grimm Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study Translational Psychiatry |
| title | Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study |
| title_full | Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study |
| title_fullStr | Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study |
| title_full_unstemmed | Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study |
| title_short | Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study |
| title_sort | functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing a double blind randomized controlled fmri study |
| url | https://doi.org/10.1038/s41398-024-03120-6 |
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