Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02346-0 |
| _version_ | 1797863463825965056 |
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| author | Lena Vera Danyeli Zümrüt Duygu Sen Lejla Colic Lisa Kurzweil Sabrina Gensberger-Reigl Tamar Macharadze Florian Götting Alexander Refisch Thomas Liebe Tara Chand Moritz Kretzschmar Gerd Wagner Nils Opel Fabrice Jollant Oliver Speck Matthias H. J. Munk Meng Li Martin Walter |
| author_facet | Lena Vera Danyeli Zümrüt Duygu Sen Lejla Colic Lisa Kurzweil Sabrina Gensberger-Reigl Tamar Macharadze Florian Götting Alexander Refisch Thomas Liebe Tara Chand Moritz Kretzschmar Gerd Wagner Nils Opel Fabrice Jollant Oliver Speck Matthias H. J. Munk Meng Li Martin Walter |
| author_sort | Lena Vera Danyeli |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T22:36:00Z |
| format | Article |
| id | doaj.art-64d55303faf4408db4e8ccf21e4d866a |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-09T22:36:00Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-64d55303faf4408db4e8ccf21e4d866a2023-03-22T12:27:14ZengNature Publishing GroupTranslational Psychiatry2158-31882023-02-011311910.1038/s41398-023-02346-0Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamineLena Vera Danyeli0Zümrüt Duygu Sen1Lejla Colic2Lisa Kurzweil3Sabrina Gensberger-Reigl4Tamar Macharadze5Florian Götting6Alexander Refisch7Thomas Liebe8Tara Chand9Moritz Kretzschmar10Gerd Wagner11Nils Opel12Fabrice Jollant13Oliver Speck14Matthias H. J. Munk15Meng Li16Martin Walter17Department of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalFood Chemistry, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-NürnbergFood Chemistry, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Anesthesiology and Intensive Care Medicine, Medical Faculty, Otto-von-Guericke-Universität MagdeburgDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Anesthesiology and Intensive Care Medicine, Medical Faculty, Otto-von-Guericke-Universität MagdeburgDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalCenter for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C)Department of Psychiatry and Psychotherapy, University TübingenDepartment of Psychiatry and Psychotherapy, Jena University HospitalDepartment of Psychiatry and Psychotherapy, Jena University HospitalAbstract 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.https://doi.org/10.1038/s41398-023-02346-0 |
| spellingShingle | Lena Vera Danyeli Zümrüt Duygu Sen Lejla Colic Lisa Kurzweil Sabrina Gensberger-Reigl Tamar Macharadze Florian Götting Alexander Refisch Thomas Liebe Tara Chand Moritz Kretzschmar Gerd Wagner Nils Opel Fabrice Jollant Oliver Speck Matthias H. J. Munk Meng Li Martin Walter Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine Translational Psychiatry |
| 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 |
| url | https://doi.org/10.1038/s41398-023-02346-0 |
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