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Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males

Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within th...

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Autores principales: Yang, Ruoting, Gautam, Aarti, Getnet, Derese, Daigle, Bernie J., Miller, Stacy, Misganaw, Burook, Dean, Kelsey R., Kumar, Raina, Muhie, Seid, Wang, Kai, Lee, Inyoul, Abu-Amara, Duna, Flory, Janine D., Hood, Leroy, Wolkowitz, Owen M., Mellon, Synthia H., Doyle, Francis J., Yehuda, Rachel, Marmar, Charles R., Ressler, Kerry J., Hammamieh, Rasha, Jett, Marti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550967/
https://www.ncbi.nlm.nih.gov/pubmed/33339956
http://dx.doi.org/10.1038/s41380-020-00966-2
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author Yang, Ruoting
Gautam, Aarti
Getnet, Derese
Daigle, Bernie J.
Miller, Stacy
Misganaw, Burook
Dean, Kelsey R.
Kumar, Raina
Muhie, Seid
Wang, Kai
Lee, Inyoul
Abu-Amara, Duna
Flory, Janine D.
Hood, Leroy
Wolkowitz, Owen M.
Mellon, Synthia H.
Doyle, Francis J.
Yehuda, Rachel
Marmar, Charles R.
Ressler, Kerry J.
Hammamieh, Rasha
Jett, Marti
author_facet Yang, Ruoting
Gautam, Aarti
Getnet, Derese
Daigle, Bernie J.
Miller, Stacy
Misganaw, Burook
Dean, Kelsey R.
Kumar, Raina
Muhie, Seid
Wang, Kai
Lee, Inyoul
Abu-Amara, Duna
Flory, Janine D.
Hood, Leroy
Wolkowitz, Owen M.
Mellon, Synthia H.
Doyle, Francis J.
Yehuda, Rachel
Marmar, Charles R.
Ressler, Kerry J.
Hammamieh, Rasha
Jett, Marti
author_sort Yang, Ruoting
collection PubMed
description Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within the PTSD group observed following epigenome-wide analysis of a well-characterized Discovery cohort (N = 166) consisting of 83 male combat exposed veterans with PTSD, and 83 combat veterans without PTSD in order to identify patterns that might distinguish subtypes. Computational analysis of DNA methylation (DNAm) profiles identified two PTSD biotypes within the PTSD+ group, G1 and G2, associated with 34 clinical features that are associated with PTSD and PTSD comorbidities. The G2 biotype was associated with an increased PTSD risk and had higher polygenic risk scores and a greater methylation compared to the G1 biotype and healthy controls. The findings were validated at a 3-year follow-up (N = 59) of the same individuals as well as in two independent, veteran cohorts (N = 54 and N = 38), and an active duty cohort (N = 133). In some cases, for example Dopamine-PKA-CREB and GABA-PKC-CREB signaling pathways, the biotypes were oppositely dysregulated, suggesting that the biotypes were not simply a function of a dimensional relationship with symptom severity, but may represent distinct biological risk profiles underpinning PTSD. The identification of two novel distinct epigenetic biotypes for PTSD may have future utility in understanding biological and clinical heterogeneity in PTSD and potential applications in risk assessment for active duty military personnel under non-clinician-administered settings, and improvement of PTSD diagnostic markers.
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spelling pubmed-85509672021-11-10 Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males Yang, Ruoting Gautam, Aarti Getnet, Derese Daigle, Bernie J. Miller, Stacy Misganaw, Burook Dean, Kelsey R. Kumar, Raina Muhie, Seid Wang, Kai Lee, Inyoul Abu-Amara, Duna Flory, Janine D. Hood, Leroy Wolkowitz, Owen M. Mellon, Synthia H. Doyle, Francis J. Yehuda, Rachel Marmar, Charles R. Ressler, Kerry J. Hammamieh, Rasha Jett, Marti Mol Psychiatry Article Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within the PTSD group observed following epigenome-wide analysis of a well-characterized Discovery cohort (N = 166) consisting of 83 male combat exposed veterans with PTSD, and 83 combat veterans without PTSD in order to identify patterns that might distinguish subtypes. Computational analysis of DNA methylation (DNAm) profiles identified two PTSD biotypes within the PTSD+ group, G1 and G2, associated with 34 clinical features that are associated with PTSD and PTSD comorbidities. The G2 biotype was associated with an increased PTSD risk and had higher polygenic risk scores and a greater methylation compared to the G1 biotype and healthy controls. The findings were validated at a 3-year follow-up (N = 59) of the same individuals as well as in two independent, veteran cohorts (N = 54 and N = 38), and an active duty cohort (N = 133). In some cases, for example Dopamine-PKA-CREB and GABA-PKC-CREB signaling pathways, the biotypes were oppositely dysregulated, suggesting that the biotypes were not simply a function of a dimensional relationship with symptom severity, but may represent distinct biological risk profiles underpinning PTSD. The identification of two novel distinct epigenetic biotypes for PTSD may have future utility in understanding biological and clinical heterogeneity in PTSD and potential applications in risk assessment for active duty military personnel under non-clinician-administered settings, and improvement of PTSD diagnostic markers. Nature Publishing Group UK 2020-12-18 2021 /pmc/articles/PMC8550967/ /pubmed/33339956 http://dx.doi.org/10.1038/s41380-020-00966-2 Text en © The Author(s) 2020 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
Yang, Ruoting
Gautam, Aarti
Getnet, Derese
Daigle, Bernie J.
Miller, Stacy
Misganaw, Burook
Dean, Kelsey R.
Kumar, Raina
Muhie, Seid
Wang, Kai
Lee, Inyoul
Abu-Amara, Duna
Flory, Janine D.
Hood, Leroy
Wolkowitz, Owen M.
Mellon, Synthia H.
Doyle, Francis J.
Yehuda, Rachel
Marmar, Charles R.
Ressler, Kerry J.
Hammamieh, Rasha
Jett, Marti
Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
title Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
title_full Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
title_fullStr Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
title_full_unstemmed Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
title_short Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
title_sort epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550967/
https://www.ncbi.nlm.nih.gov/pubmed/33339956
http://dx.doi.org/10.1038/s41380-020-00966-2
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