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A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder

Gliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO V(T)), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission t...

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Autores principales: Attwells, Sophia, Setiawan, Elaine, Rusjan, Pablo M., Xu, Cynthia, Kish, Stephen J., Vasdev, Neil, Houle, Sylvain, Santhirakumar, Apitharani, Meyer, Jeffrey H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164633/
https://www.ncbi.nlm.nih.gov/pubmed/34052828
http://dx.doi.org/10.1038/s41398-021-01450-3
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author Attwells, Sophia
Setiawan, Elaine
Rusjan, Pablo M.
Xu, Cynthia
Kish, Stephen J.
Vasdev, Neil
Houle, Sylvain
Santhirakumar, Apitharani
Meyer, Jeffrey H.
author_facet Attwells, Sophia
Setiawan, Elaine
Rusjan, Pablo M.
Xu, Cynthia
Kish, Stephen J.
Vasdev, Neil
Houle, Sylvain
Santhirakumar, Apitharani
Meyer, Jeffrey H.
author_sort Attwells, Sophia
collection PubMed
description Gliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO V(T)), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission tomography (PET). Minocycline reduces gliosis and translocator protein binding in rodents, but this is not established in humans. Here, the ability of oral minocycline to reduce TSPO V(T) was assessed in TRD. To determine whether oral minocycline, as compared to placebo, can reduce prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insula TSPO V(T) in TRD, twenty-one TRD participants underwent two [(18)F]FEPPA PET scans to measure TSPO V(T). These were completed before and after either oral minocycline 100 mg bid or placebo which was administered in a randomized double-blinded fashion for 8 weeks. There was no significant difference between the minocycline and placebo groups on change in TSPO V(T) within the PFC, ACC, and insula (repeated measures ANOVA, effect of group interaction, PFC: F(1,19) = 0.28, P = 0.60; ACC: F(1,19) = 0.54, P = 0.47; insula F(1,19) = 1.6, P = 0.22). Oral minocycline had no significant effect on TSPO V(T) which suggests that this dosage is insufficient to reduce gliosis in TRD. To target gliosis in TRD either alternative therapeutics or intravenous formulations of minocycline should be investigated. These results also suggest that across neuropsychiatric diseases in humans, it should be assumed that oral minocycline will not reduce TSPO V(T) or gliosis unless empirically demonstrated.
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spelling pubmed-81646332021-06-15 A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder Attwells, Sophia Setiawan, Elaine Rusjan, Pablo M. Xu, Cynthia Kish, Stephen J. Vasdev, Neil Houle, Sylvain Santhirakumar, Apitharani Meyer, Jeffrey H. Transl Psychiatry Article Gliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO V(T)), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission tomography (PET). Minocycline reduces gliosis and translocator protein binding in rodents, but this is not established in humans. Here, the ability of oral minocycline to reduce TSPO V(T) was assessed in TRD. To determine whether oral minocycline, as compared to placebo, can reduce prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insula TSPO V(T) in TRD, twenty-one TRD participants underwent two [(18)F]FEPPA PET scans to measure TSPO V(T). These were completed before and after either oral minocycline 100 mg bid or placebo which was administered in a randomized double-blinded fashion for 8 weeks. There was no significant difference between the minocycline and placebo groups on change in TSPO V(T) within the PFC, ACC, and insula (repeated measures ANOVA, effect of group interaction, PFC: F(1,19) = 0.28, P = 0.60; ACC: F(1,19) = 0.54, P = 0.47; insula F(1,19) = 1.6, P = 0.22). Oral minocycline had no significant effect on TSPO V(T) which suggests that this dosage is insufficient to reduce gliosis in TRD. To target gliosis in TRD either alternative therapeutics or intravenous formulations of minocycline should be investigated. These results also suggest that across neuropsychiatric diseases in humans, it should be assumed that oral minocycline will not reduce TSPO V(T) or gliosis unless empirically demonstrated. Nature Publishing Group UK 2021-05-29 /pmc/articles/PMC8164633/ /pubmed/34052828 http://dx.doi.org/10.1038/s41398-021-01450-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Attwells, Sophia
Setiawan, Elaine
Rusjan, Pablo M.
Xu, Cynthia
Kish, Stephen J.
Vasdev, Neil
Houle, Sylvain
Santhirakumar, Apitharani
Meyer, Jeffrey H.
A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
title A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
title_full A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
title_fullStr A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
title_full_unstemmed A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
title_short A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
title_sort double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164633/
https://www.ncbi.nlm.nih.gov/pubmed/34052828
http://dx.doi.org/10.1038/s41398-021-01450-3
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