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

**Authors:** Leonard Marx, Zümrüt Duygu Sen, Lena Vera Danyeli, Meng Li, Tanja Brigadski, Volkmar Leßmann, Martin Walter

PMC · DOI: 10.3389/fpsyt.2025.1662051 · 2025-10-31

## TL;DR

The study explores how ketamine affects glutamate and BDNF levels in the brain and blood, suggesting a link between these changes in healthy individuals.

## Contribution

The study provides initial in vivo evidence linking ketamine's glutamatergic effects to changes in BDNF levels.

## Key findings

- A significant interaction was found between treatment condition and glutamate changes on BDNF levels.
- A trend-level positive correlation between glutamate and BDNF changes was observed in the ketamine group.

## Abstract

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.

## Linked entities

- **Proteins:** BDNF (brain derived neurotrophic factor)
- **Chemicals:** ketamine (PubChem CID 3821), glutamate (PubChem CID 611)

## Full-text entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}
- **Chemicals:** Glu (MESH:D018698), Ketamine (MESH:D007649), 1H (-), S-ketamine (MESH:C000629870)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12616132/full.md

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Source: https://tomesphere.com/paper/PMC12616132