Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Irina Esterlis, Nicole DellaGioia, Robert H Pietrzak, D. Matuskey, N. Nabulsi, Chadi G. Abdallah, Jie Yang, Christopher Pittenger, Gerard Sanacora, J. Krystal, R. Parsey, Richard E. Carson, Christine DeLorenzo
Molecular Psychiatry April 11, 2017 DOI: 10.1038/mp.2017.58 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational case-control PET imaging study Peer reviewed |
|---|---|
| Sample size | 26 |
| Population | 13 nonsmoking individuals with major depressive disorder and 13 healthy nonsmoking controls |
| Intervention | Ketamine |
| Duration | Two PET scans on the same day (before and during ketamine) and a third scan 1 day later |
| Measures | [11C]ABP688 PET binding |
| Topics | Depression Esketamine Ketamine |
| Key findings | Ketamine administration reduced mGluR5 availability ([11C]ABP688 binding) by an average of 14±9% in MDD participants and 19±22% in healthy controls, with the reduction persisting 24 hours later. MDD participants had lower baseline binding than controls. Depressive symptoms decreased significantly after ketamine in the MDD group, and this reduction was associated with the immediate change in binding. The authors hypothesize that glutamate released after ketamine moderates mGluR5 availability and that this change relates to antidepressant efficacy. |
Abstract
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [11C]ABP688 positron emission tomography (PET) scans on the same day—before and during intravenous ketamine administration—and a third scan 1 day later. At baseline, significantly lower [11C]ABP688 binding was detected in the MDD as compared with the control group. We observed a significant ketamine-induced reduction in mGluR5 availability (that is, [11C]ABP688 binding) in both MDD and control subjects (average of 14±9% and 19±22%, respectively; P<0.01 for both), which persisted 24 h later. There were no differences in ketamine-induced changes between MDD and control groups at either time point (P=0.8). A significant reduction in depressive symptoms was observed following ketamine administration in the MDD group (P<0.001), which was associated with the change in binding (P<0.04) immediately after ketamine. We hypothesize that glutamate released after ketamine administration moderates mGluR5 availability; this change appears to be related to antidepressant efficacy. The sustained decrease in binding may reflect prolonged mGluR5 internalization in response to the glutamate surge.
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 |
Citations in the library
Cited by 32
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments Proceedings of the National Academy of Sciences November 27, 2023
- Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression JAMA Network Open August 12, 2020
and 27 more in the library
Cites 7
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
and 2 more in the library