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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)

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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.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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