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Lower synaptic density is associated with depression severity and network alterations

Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect esti...

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Autores principales: Holmes, Sophie E., Scheinost, Dustin, Finnema, Sjoerd J., Naganawa, Mika, Davis, Margaret T., DellaGioia, Nicole, Nabulsi, Nabeel, Matuskey, David, Angarita, Gustavo A., Pietrzak, Robert H., Duman, Ronald S., Sanacora, Gerard, Krystal, John H., Carson, Richard E., Esterlis, Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449365/
https://www.ncbi.nlm.nih.gov/pubmed/30948709
http://dx.doi.org/10.1038/s41467-019-09562-7
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author Holmes, Sophie E.
Scheinost, Dustin
Finnema, Sjoerd J.
Naganawa, Mika
Davis, Margaret T.
DellaGioia, Nicole
Nabulsi, Nabeel
Matuskey, David
Angarita, Gustavo A.
Pietrzak, Robert H.
Duman, Ronald S.
Sanacora, Gerard
Krystal, John H.
Carson, Richard E.
Esterlis, Irina
author_facet Holmes, Sophie E.
Scheinost, Dustin
Finnema, Sjoerd J.
Naganawa, Mika
Davis, Margaret T.
DellaGioia, Nicole
Nabulsi, Nabeel
Matuskey, David
Angarita, Gustavo A.
Pietrzak, Robert H.
Duman, Ronald S.
Sanacora, Gerard
Krystal, John H.
Carson, Richard E.
Esterlis, Irina
author_sort Holmes, Sophie E.
collection PubMed
description Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [(11)C]UCB-J to examine synaptic density in n = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD. The severity of depressive symptoms was inversely correlated with SV2A density, and individuals with high levels of depression showing lower SV2A density compared to healthy controls (n = 21). SV2A density was also associated with aberrant network function, as measured by magnetic resonance imaging (MRI) functional connectivity. This is the first in vivo evidence linking lower synaptic density to network alterations and symptoms of depression. Our findings provide further incentive to evaluate interventions that restore synaptic connections to treat depression.
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spelling pubmed-64493652019-04-08 Lower synaptic density is associated with depression severity and network alterations Holmes, Sophie E. Scheinost, Dustin Finnema, Sjoerd J. Naganawa, Mika Davis, Margaret T. DellaGioia, Nicole Nabulsi, Nabeel Matuskey, David Angarita, Gustavo A. Pietrzak, Robert H. Duman, Ronald S. Sanacora, Gerard Krystal, John H. Carson, Richard E. Esterlis, Irina Nat Commun Article Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [(11)C]UCB-J to examine synaptic density in n = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD. The severity of depressive symptoms was inversely correlated with SV2A density, and individuals with high levels of depression showing lower SV2A density compared to healthy controls (n = 21). SV2A density was also associated with aberrant network function, as measured by magnetic resonance imaging (MRI) functional connectivity. This is the first in vivo evidence linking lower synaptic density to network alterations and symptoms of depression. Our findings provide further incentive to evaluate interventions that restore synaptic connections to treat depression. Nature Publishing Group UK 2019-04-04 /pmc/articles/PMC6449365/ /pubmed/30948709 http://dx.doi.org/10.1038/s41467-019-09562-7 Text en © The Author(s) 2019 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
Holmes, Sophie E.
Scheinost, Dustin
Finnema, Sjoerd J.
Naganawa, Mika
Davis, Margaret T.
DellaGioia, Nicole
Nabulsi, Nabeel
Matuskey, David
Angarita, Gustavo A.
Pietrzak, Robert H.
Duman, Ronald S.
Sanacora, Gerard
Krystal, John H.
Carson, Richard E.
Esterlis, Irina
Lower synaptic density is associated with depression severity and network alterations
title Lower synaptic density is associated with depression severity and network alterations
title_full Lower synaptic density is associated with depression severity and network alterations
title_fullStr Lower synaptic density is associated with depression severity and network alterations
title_full_unstemmed Lower synaptic density is associated with depression severity and network alterations
title_short Lower synaptic density is associated with depression severity and network alterations
title_sort lower synaptic density is associated with depression severity and network alterations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449365/
https://www.ncbi.nlm.nih.gov/pubmed/30948709
http://dx.doi.org/10.1038/s41467-019-09562-7
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