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 January 1, 2025 DOI: 10.3389/fpsyt.2025.1662051 via PubMed
Summary
AI-generated from the abstractKetamine's rapid antidepressant effects are thought to involve glutamate signaling and brain-derived neurotrophic factor (BDNF), but how these two factors interact is unclear. In a randomized, placebo-controlled crossover study with 35 healthy men, researchers measured glutamate levels in the pregenual anterior cingulate cortex using 7 Tesla magnetic resonance spectroscopy and plasma BDNF levels before and after infusions of S-ketamine or placebo. A significant interaction emerged between treatment condition and changes in glutamate on BDNF level changes, with a trend-level positive correlation between glutamate and BDNF changes only in the ketamine group. These findings offer initial in vivo evidence that ketamine's influence on BDNF is tied to its glutamatergic action.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Healthy male subjects |
| Intervention | S-ketamine |
| Duration | 24 hours |
| Topics | Depression Ketamine |
| Keywords | Anterior cingulate cortex Brain-derived neurotrophic factor Magnetic resonance spectroscopy Ketamine antidepressant ketamine Depression treatment |
| Key finding | 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.