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

Danyeli LV, Sen ZD, Colic L, Kurzweil L, Gensberger-Reigl S, Macharadze T, Götting F, Refisch A, Liebe T, Chand T, Kretzschmar M, Wagner G, Opel N, Jollant F, Speck O, Munk MH, Li M, Walter M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Translational Psychiatry Springer Nature

Book Volume: 13

Article Number: 60

Journal Issue: 1

DOI: 10.1038/s41398-023-02346-0

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 (pFWEc) = 0.018) and dorsolateral prefrontal cortex (PFC; pFWEc = 0.002) was detected that was preceded by an immediate rsFC increase of the pgACC to medial PFC (pFWEc < 0.001) and dorsomedial PFC (pFWEc = 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.

Authors with CRIS profile

Lisa Kurzweil Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl) Sabrina Gensberger-Reigl Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)

Involved external institutions

Universitätsklinikum Jena DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE)

How to cite

APA:

Danyeli, L.V., Sen, Z.D., Colic, L., Kurzweil, L., Gensberger-Reigl, S., Macharadze, T.,... Walter, M. (2023). Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine. Translational Psychiatry, 13(1). https://doi.org/10.1038/s41398-023-02346-0

MLA:

Danyeli, Lena Vera, et al. "Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine." Translational Psychiatry 13.1 (2023).

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