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A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression
The glutamate N-methyl-d-aspartate receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be d...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261801/ https://www.ncbi.nlm.nih.gov/pubmed/32475989 http://dx.doi.org/10.1038/s41398-020-0844-4 |
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author | Tiger, Mikael Veldman, Emma R. Ekman, Carl-Johan Halldin, Christer Svenningsson, Per Lundberg, Johan |
author_facet | Tiger, Mikael Veldman, Emma R. Ekman, Carl-Johan Halldin, Christer Svenningsson, Per Lundberg, Johan |
author_sort | Tiger, Mikael |
collection | PubMed |
description | The glutamate N-methyl-d-aspartate receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the serotonin (5-HT)(1B) receptor. Low 5-HT(1B) receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT(1B) receptor binding in the ventral striatum (VST) has been demonstrated after ketamine infusion. Thirty selective serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT(1B) receptor selective radioligand [(11)C]AZ10419369 and positron emission tomography (PET) before and 24–72 h after treatment. 5-HT(1B) receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT(1B) receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT(1B) receptor binding in VST at baseline correlated with MDD symptom ratings (r = −0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = −0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT(1B) receptor binding in VST. Further studies examining the role of 5-HT(1B) receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT(1B) receptor as an MDD treatment response marker. |
format | Online Article Text |
id | pubmed-7261801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72618012020-06-10 A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression Tiger, Mikael Veldman, Emma R. Ekman, Carl-Johan Halldin, Christer Svenningsson, Per Lundberg, Johan Transl Psychiatry Article The glutamate N-methyl-d-aspartate receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the serotonin (5-HT)(1B) receptor. Low 5-HT(1B) receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT(1B) receptor binding in the ventral striatum (VST) has been demonstrated after ketamine infusion. Thirty selective serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT(1B) receptor selective radioligand [(11)C]AZ10419369 and positron emission tomography (PET) before and 24–72 h after treatment. 5-HT(1B) receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT(1B) receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT(1B) receptor binding in VST at baseline correlated with MDD symptom ratings (r = −0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = −0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT(1B) receptor binding in VST. Further studies examining the role of 5-HT(1B) receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT(1B) receptor as an MDD treatment response marker. Nature Publishing Group UK 2020-06-01 /pmc/articles/PMC7261801/ /pubmed/32475989 http://dx.doi.org/10.1038/s41398-020-0844-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tiger, Mikael Veldman, Emma R. Ekman, Carl-Johan Halldin, Christer Svenningsson, Per Lundberg, Johan A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression |
title | A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression |
title_full | A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression |
title_fullStr | A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression |
title_full_unstemmed | A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression |
title_short | A randomized placebo-controlled PET study of ketamine´s effect on serotonin(1B) receptor binding in patients with SSRI-resistant depression |
title_sort | randomized placebo-controlled pet study of ketamine´s effect on serotonin(1b) receptor binding in patients with ssri-resistant depression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261801/ https://www.ncbi.nlm.nih.gov/pubmed/32475989 http://dx.doi.org/10.1038/s41398-020-0844-4 |
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