AUTHOR=Marx Leonard , Sen Zümrüt Duygu , Danyeli Lena Vera , Li Meng , Brigadski Tanja , Leßmann Volkmar , Walter Martin 

TITLE=Association between S-ketamine induced changes in glutamate levels in the pregenual anterior cingulate cortex and plasma brain-derived neurotrophic factor in healthy subjects

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1662051

DOI=10.3389/fpsyt.2025.1662051

ISSN=1664-0640

ABSTRACT=IntroductionKetamine’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.MethodsThis 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.ResultsLinear 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.DiscussionThese findings provide initial in vivo support for the hypothesis that ketamine’s effects on BDNF dynamics are linked to its glutamatergic action.