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Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder

The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of t...

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Autores principales: Breen, Michael S., Maihofer, Adam X., Glatt, Stephen J., Tylee, Daniel S., Chandler, Sharon D., Tsuang, Ming T., Risbrough, Victoria B., Baker, Dewleen G., O’Connor, Daniel T., Nievergelt, Caroline M., Woelk, Christopher H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565790/
https://www.ncbi.nlm.nih.gov/pubmed/25754082
http://dx.doi.org/10.1038/mp.2015.9
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author Breen, Michael S.
Maihofer, Adam X.
Glatt, Stephen J.
Tylee, Daniel S.
Chandler, Sharon D.
Tsuang, Ming T.
Risbrough, Victoria B.
Baker, Dewleen G.
O’Connor, Daniel T.
Nievergelt, Caroline M.
Woelk, Christopher H.
author_facet Breen, Michael S.
Maihofer, Adam X.
Glatt, Stephen J.
Tylee, Daniel S.
Chandler, Sharon D.
Tsuang, Ming T.
Risbrough, Victoria B.
Baker, Dewleen G.
O’Connor, Daniel T.
Nievergelt, Caroline M.
Woelk, Christopher H.
author_sort Breen, Michael S.
collection PubMed
description The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD.
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spelling pubmed-45657902016-05-18 Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder Breen, Michael S. Maihofer, Adam X. Glatt, Stephen J. Tylee, Daniel S. Chandler, Sharon D. Tsuang, Ming T. Risbrough, Victoria B. Baker, Dewleen G. O’Connor, Daniel T. Nievergelt, Caroline M. Woelk, Christopher H. Mol Psychiatry Article The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. 2015-03-10 2015-12 /pmc/articles/PMC4565790/ /pubmed/25754082 http://dx.doi.org/10.1038/mp.2015.9 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Breen, Michael S.
Maihofer, Adam X.
Glatt, Stephen J.
Tylee, Daniel S.
Chandler, Sharon D.
Tsuang, Ming T.
Risbrough, Victoria B.
Baker, Dewleen G.
O’Connor, Daniel T.
Nievergelt, Caroline M.
Woelk, Christopher H.
Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder
title Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder
title_full Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder
title_fullStr Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder
title_full_unstemmed Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder
title_short Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder
title_sort gene networks specific for innate immunity define post-traumatic stress disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565790/
https://www.ncbi.nlm.nih.gov/pubmed/25754082
http://dx.doi.org/10.1038/mp.2015.9
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