Acute ketamine administration modulates glutamatergic neurotransmission and functional brain activation in prefrontal cortex implications for major depression
Milan Scheidegger, Anke Henning, Martin Walter, Alexander Fuchs, Rainer Krähenmann, Heinz Böker, Peter Bösiger, Erich Seifritz, Simone Grimm
Pharmacopsychiatry September 1, 2011 DOI: 10.1055/s-0031-1292539 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy subjects |
| Intervention | S-ketamine |
| Dose | 0.12 mg/kg i.v. bolus followed by 0.25 mg/kg/h over 60 min |
| Duration | 60-minute infusion |
| Topics | Ketamine Depression Esketamine |
| Keywords | Glutamatergic Glutamate receptor Nmda receptor Anterior cingulate cortex Prefrontal cortex Glutamine Neurotransmission Pharmacology Antidepressant Anesthesia Cognition Hippocampus |
| Key findings | Changes in fMRI-BOLD responses during emotional processing correlated with glutamine to glutamate ratios in the pregenual anterior cingulate cortex after ketamine administration, suggesting increased glutamate-glutamine cycling. |
Abstract
Background: Ketamine is a potent NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses. This multimodal imaging study reveals the effects of a subanaesthetic ketamine infusion on fMRI-BOLD responses during an emotional processing task and their relationship to glutamatergic metabolite concentrations in the pregenual anterior cingulate cortex (PACC) assessed by proton magnetic resonance spectroscopy (1H-MRS).
Methods: 23 healthy subjects were asked to judge photographs from the International Affective Picture System (IAPS) by button press according to their valence in two separate fMRI sessions (baseline/ketamine) on a Philips 3T MR unit. S-ketamine was administered as an i.v. bolus of 0.12 mg/kg, followed by an infusion of 0.25 mg/kg/h over 60 min. 1H-MRS spectra from the bilateral PACC could be obtained in 16 subjects immediately after the task using a JPRESS sequence. Results and
Conclusion: In the PACC, changes in NBRs correlated with glutamine to glutamate ratios as a putative marker of glutamatergic neurotransmission after ketamine administration compared to baseline. These changes are most likely interpreted in terms of an increased glutamate-glutamine-cycling rate after ketamine administration. Thus, the antidepressant effect of ketamine might be linked to a beneficial short-term influence on glutamatergic neurotransmission.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |