ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1662051
This article is part of the Research TopicBridging the Gap: An Interdisciplinary Perspective on Ketamine in Psychiatric Disorders - Volume IIIView all articles
Association between S-ketamine induced changes in glutamate levels in the pregenual anterior cingulate cortex and plasma brain-derived neurotrophic factor in healthy subjects
Provisionally accepted
Leonard Marx1
Zumrut Duygu Sen1,2,3Lena Vera Danyeli1,2,3
Tanja Brigadski4,5
Volkmar Lessmann2,3,4
Martin Walter2,3,6*- 1Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany
- 2Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Halle-Jena-Magdeburg, Germany
- 3Deutsches Zentrum fur Psychische Gesundheit, Mannheim, Germany
- 4Otto-von-Guericke-Universitat Magdeburg Institut fur Physiologie, Magdeburg, Germany
- 5Hochschule Kaiserslautern - Standort Zweibrucken, Zweibrücken, Germany
- 6University Hospital Jena, Jena, Germany
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Ketamine's antidepressant effects have been linked to its modulation of glutamatergic neurotransmission and synaptic plasticity. However, the precise roles of both glutamate (Glu) levels and brain-derived neurotrophic factor (BDNF) in this process remain incompletely understood. This study examined the relationship between ketamine-induced changes in Glu levels and peripheral BDNF levels using data from a randomized, placebo-controlled crossover design. Proton magnetic resonance spectroscopy (7 Tesla 1H-MRS) assessing Glu concentrations in the pregenual anterior cingulate cortex (pgACC) and plasma BDNF levels were measured one hour before and 24 hours after either S-ketamine or placebo infusions in 35 healthy male subjects. Linear regression analysis revealed a significant interaction between treatment condition and relative changes in Glu on BDNF level changes, with a trend-level positive correlation between changes in Glu and BDNF levels observed only in the ketamine group. These findings provide initial in vivo support for the hypothesis that ketamine's effects on BDNF dynamics are linked to its glutamatergic action.
Keywords: Ketamine, Glutamate, Brain-Derived Neurotrophic Factor, Magnetic Resonance Spectroscopy, anteriorcingulate cortex, Depression
Received: 08 Jul 2025; Accepted: 01 Oct 2025.
Copyright: © 2025 Marx, Sen, Danyeli, Brigadski, Lessmann and Walter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Martin Walter, martin.walter@med.uni-jena.de
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