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Gene networks specific for innate immunity define post-traumatic stress disorder

Gene networks specific for innate immunity define post-traumatic stress disorder
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 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.
1359-4184
Breen, M.S.
315d6131-b831-4b6c-a7f9-d0b9957d6f18
Maihofer, A.X.
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Glatt, S.J.
277ea1bc-88a1-4a1b-823b-36430178afa7
Tylee, D.S.
9f27fff5-f183-46d3-850e-065914f2f3fd
Chandler, S.D.
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Tsuang, M.T.
88753f4e-dfe9-4f3f-b7aa-ae8372003ddf
Risbrough, V.B.
0230ffb5-8baa-4056-accd-754b85265283
Baker, D.G.
a68cca4f-3af3-4283-aad8-e1a54fe37258
O'Connor, D.T.
8e21649e-b19a-4503-9bcb-2f47a65a160c
Nievergelt, C.M.
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Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Breen, M.S.
315d6131-b831-4b6c-a7f9-d0b9957d6f18
Maihofer, A.X.
2c3c04cd-a902-4ac1-8fbc-87d36b5f6270
Glatt, S.J.
277ea1bc-88a1-4a1b-823b-36430178afa7
Tylee, D.S.
9f27fff5-f183-46d3-850e-065914f2f3fd
Chandler, S.D.
5315fc01-02b4-4059-8d9b-124413b9da01
Tsuang, M.T.
88753f4e-dfe9-4f3f-b7aa-ae8372003ddf
Risbrough, V.B.
0230ffb5-8baa-4056-accd-754b85265283
Baker, D.G.
a68cca4f-3af3-4283-aad8-e1a54fe37258
O'Connor, D.T.
8e21649e-b19a-4503-9bcb-2f47a65a160c
Nievergelt, C.M.
5646467c-4616-4334-98cf-9098050490b1
Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d

Breen, M.S., Maihofer, A.X., Glatt, S.J., Tylee, D.S., Chandler, S.D., Tsuang, M.T., Risbrough, V.B., Baker, D.G., O'Connor, D.T., Nievergelt, C.M. and Woelk, C.H. (2015) Gene networks specific for innate immunity define post-traumatic stress disorder. Molecular Psychiatry. (doi:10.1038/mp.2015.9).

Record type: Article

Abstract

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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More information

Accepted/In Press date: 10 March 2015
e-pub ahead of print date: 10 March 2015
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 379217
URI: https://eprints.soton.ac.uk/id/eprint/379217
ISSN: 1359-4184
PURE UUID: f3008554-609c-41ed-a21e-b0f6f7906fbb

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Date deposited: 18 Jul 2015 14:52
Last modified: 04 Jul 2018 16:30

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Contributors

Author: M.S. Breen
Author: A.X. Maihofer
Author: S.J. Glatt
Author: D.S. Tylee
Author: S.D. Chandler
Author: M.T. Tsuang
Author: V.B. Risbrough
Author: D.G. Baker
Author: D.T. O'Connor
Author: C.M. Nievergelt
Author: C.H. Woelk

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