Association between S-ketamine induced changes in glutamate levels in the pregenual anterior cingulate cortex and plasma brain-derived neurotrophic factor in healthy subjects.
Leonard Marx, Zümrüt Duygu Sen, Lena Vera Danyeli, Meng Li, Tanja Brigadski, Volkmar Leßmann, Martin Walter
Frontiers in Psychiatry 2025 DOI: 10.3389/fpsyt.2025.1662051 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Healthy male subjects |
| Intervention | S-ketamine |
| Duration | 24 hours |
| Topics | Depression Ketamine Esketamine |
| Keywords | Anterior cingulate cortex Brain-derived neurotrophic factor Magnetic resonance spectroscopy Ketamine antidepressant ketamine Depression treatment Rapid antidepressant potential Glutamatergic action Brain changes Brain health Glutamate levels Mrs Brain imaging |
| Key findings | Ketamine-induced changes in glutamate levels in the pregenual anterior cingulate cortex were linked to changes in peripheral BDNF levels, supporting a connection between glutamatergic action and BDNF dynamics. |
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.