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Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine

Ketamine shows rapid antidepressant effects peaking 24 h after administration. The antidepressant effects may occur through changes in glutamatergic metabolite levels and resting-state functional connectivity (rsFC) within the default mode network (DMN). A multistage drug effect of ketamine has been...

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Autores principales: Danyeli, Lena Vera, Sen, Zümrüt Duygu, Colic, Lejla, Kurzweil, Lisa, Gensberger-Reigl, Sabrina, Macharadze, Tamar, Götting, Florian, Refisch, Alexander, Liebe, Thomas, Chand, Tara, Kretzschmar, Moritz, Wagner, Gerd, Opel, Nils, Jollant, Fabrice, Speck, Oliver, Munk, Matthias H. J., Li, Meng, Walter, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935558/
https://www.ncbi.nlm.nih.gov/pubmed/36797238
http://dx.doi.org/10.1038/s41398-023-02346-0
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author Danyeli, Lena Vera
Sen, Zümrüt Duygu
Colic, Lejla
Kurzweil, Lisa
Gensberger-Reigl, Sabrina
Macharadze, Tamar
Götting, Florian
Refisch, Alexander
Liebe, Thomas
Chand, Tara
Kretzschmar, Moritz
Wagner, Gerd
Opel, Nils
Jollant, Fabrice
Speck, Oliver
Munk, Matthias H. J.
Li, Meng
Walter, Martin
author_facet Danyeli, Lena Vera
Sen, Zümrüt Duygu
Colic, Lejla
Kurzweil, Lisa
Gensberger-Reigl, Sabrina
Macharadze, Tamar
Götting, Florian
Refisch, Alexander
Liebe, Thomas
Chand, Tara
Kretzschmar, Moritz
Wagner, Gerd
Opel, Nils
Jollant, Fabrice
Speck, Oliver
Munk, Matthias H. J.
Li, Meng
Walter, Martin
author_sort Danyeli, Lena Vera
collection PubMed
description Ketamine shows rapid antidepressant effects peaking 24 h after administration. The antidepressant effects may occur through changes in glutamatergic metabolite levels and resting-state functional connectivity (rsFC) within the default mode network (DMN). A multistage drug effect of ketamine has been suggested, inducing acute effects on dysfunctional network configuration and delayed effects on homeostatic synaptic plasticity. Whether the DMN-centered delayed antidepressant-related changes are associated with the immediate changes remains unknown. Thirty-five healthy male participants (25.1 ± 4.2 years) underwent 7 T magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rsfMRI) before, during, and 24 h after a single S-ketamine or placebo infusion. Changes in glutamatergic measures and rsFC in the DMN node pregenual anterior cingulate cortex (pgACC) were examined. A delayed rsFC decrease of the pgACC to inferior parietal lobe (family-wise error corrected p (p(FWEc)) = 0.018) and dorsolateral prefrontal cortex (PFC; p(FWEc) = 0.002) was detected that was preceded by an immediate rsFC increase of the pgACC to medial PFC (p(FWEc) < 0.001) and dorsomedial PFC (p(FWEc) = 0.005). Additionally, the immediate rsFC reconfigurations correlated with the delayed pgACC glutamate (Glu) level increase (p = 0.024) after 24 h at trend level (p = 0.067). Baseline measures of rsFC and MRS were furthermore associated with the magnitude of the respective delayed changes (p’s < 0.05). In contrast, the delayed changes were not associated with acute psychotomimetic side effects or plasma concentrations of ketamine and its metabolites. This multimodal study suggests an association between immediate S-ketamine-induced network effects and delayed brain changes at a time point relevant in its clinical context.
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spelling pubmed-99355582023-02-18 Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine Danyeli, Lena Vera Sen, Zümrüt Duygu Colic, Lejla Kurzweil, Lisa Gensberger-Reigl, Sabrina Macharadze, Tamar Götting, Florian Refisch, Alexander Liebe, Thomas Chand, Tara Kretzschmar, Moritz Wagner, Gerd Opel, Nils Jollant, Fabrice Speck, Oliver Munk, Matthias H. J. Li, Meng Walter, Martin Transl Psychiatry Article Ketamine shows rapid antidepressant effects peaking 24 h after administration. The antidepressant effects may occur through changes in glutamatergic metabolite levels and resting-state functional connectivity (rsFC) within the default mode network (DMN). A multistage drug effect of ketamine has been suggested, inducing acute effects on dysfunctional network configuration and delayed effects on homeostatic synaptic plasticity. Whether the DMN-centered delayed antidepressant-related changes are associated with the immediate changes remains unknown. Thirty-five healthy male participants (25.1 ± 4.2 years) underwent 7 T magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rsfMRI) before, during, and 24 h after a single S-ketamine or placebo infusion. Changes in glutamatergic measures and rsFC in the DMN node pregenual anterior cingulate cortex (pgACC) were examined. A delayed rsFC decrease of the pgACC to inferior parietal lobe (family-wise error corrected p (p(FWEc)) = 0.018) and dorsolateral prefrontal cortex (PFC; p(FWEc) = 0.002) was detected that was preceded by an immediate rsFC increase of the pgACC to medial PFC (p(FWEc) < 0.001) and dorsomedial PFC (p(FWEc) = 0.005). Additionally, the immediate rsFC reconfigurations correlated with the delayed pgACC glutamate (Glu) level increase (p = 0.024) after 24 h at trend level (p = 0.067). Baseline measures of rsFC and MRS were furthermore associated with the magnitude of the respective delayed changes (p’s < 0.05). In contrast, the delayed changes were not associated with acute psychotomimetic side effects or plasma concentrations of ketamine and its metabolites. This multimodal study suggests an association between immediate S-ketamine-induced network effects and delayed brain changes at a time point relevant in its clinical context. Nature Publishing Group UK 2023-02-16 /pmc/articles/PMC9935558/ /pubmed/36797238 http://dx.doi.org/10.1038/s41398-023-02346-0 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Danyeli, Lena Vera
Sen, Zümrüt Duygu
Colic, Lejla
Kurzweil, Lisa
Gensberger-Reigl, Sabrina
Macharadze, Tamar
Götting, Florian
Refisch, Alexander
Liebe, Thomas
Chand, Tara
Kretzschmar, Moritz
Wagner, Gerd
Opel, Nils
Jollant, Fabrice
Speck, Oliver
Munk, Matthias H. J.
Li, Meng
Walter, Martin
Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
title Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
title_full Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
title_fullStr Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
title_full_unstemmed Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
title_short Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
title_sort association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of s-ketamine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935558/
https://www.ncbi.nlm.nih.gov/pubmed/36797238
http://dx.doi.org/10.1038/s41398-023-02346-0
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