The University of Southampton
University of Southampton Institutional Repository

PTSD blood transcriptome mega-analysis: shared inflammatory pathways across biological sex and modes of trauma

PTSD blood transcriptome mega-analysis: shared inflammatory pathways across biological sex and modes of trauma
PTSD blood transcriptome mega-analysis: shared inflammatory pathways across biological sex and modes of trauma

Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.

0893-133X
469-481
Breen, Michael S.
2a4241cd-4f16-4f7f-9165-1459ed2c8890
Tylee, Daniel S.
9bcfee5d-4cb2-41ae-a3d2-0d4e7f7a81b1
Maihofer, Adam X.
74ecc713-f951-4933-8e8b-d0df89c74d07
Neylan, Thomas C.
690e164c-167e-4688-9d0a-7d28812c993d
Mehta, Divya
846e65d7-71b7-4247-b816-7fd8e1ae8eab
Binder, Elisabeth B.
96047fdc-dbd4-4864-b424-ab3d9da8012a
Chandler, Sharon D.
58f659ec-a938-4b98-a759-e4a72445dda8
Hess, Jonathan L.
2a180b41-0226-4c0b-bc42-4e9691d267cd
Kremen, William S.
32f31531-e6d2-4ee3-942c-ce67dad63d70
Risbrough, Victoria B.
2a9d331b-dd12-4921-95d2-0add7916e101
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Baker, Dewleen G.
a39cdf15-cb1a-4dfa-b3ff-ee9f5b2ae447
Nievergelt, Caroline M.
9308faea-edfd-4f38-b744-9698e32d1341
Tsuang, Ming T.
9cf05972-8f23-41f1-ae36-29a4fa0eff38
Buxbaum, Joseph D.
c5d8c919-2ab0-405b-9f24-1bc89b9dbf82
Glatt, Stephen J.
f8ed5b23-fc0d-4c57-a700-fbda89554592
Breen, Michael S.
2a4241cd-4f16-4f7f-9165-1459ed2c8890
Tylee, Daniel S.
9bcfee5d-4cb2-41ae-a3d2-0d4e7f7a81b1
Maihofer, Adam X.
74ecc713-f951-4933-8e8b-d0df89c74d07
Neylan, Thomas C.
690e164c-167e-4688-9d0a-7d28812c993d
Mehta, Divya
846e65d7-71b7-4247-b816-7fd8e1ae8eab
Binder, Elisabeth B.
96047fdc-dbd4-4864-b424-ab3d9da8012a
Chandler, Sharon D.
58f659ec-a938-4b98-a759-e4a72445dda8
Hess, Jonathan L.
2a180b41-0226-4c0b-bc42-4e9691d267cd
Kremen, William S.
32f31531-e6d2-4ee3-942c-ce67dad63d70
Risbrough, Victoria B.
2a9d331b-dd12-4921-95d2-0add7916e101
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Baker, Dewleen G.
a39cdf15-cb1a-4dfa-b3ff-ee9f5b2ae447
Nievergelt, Caroline M.
9308faea-edfd-4f38-b744-9698e32d1341
Tsuang, Ming T.
9cf05972-8f23-41f1-ae36-29a4fa0eff38
Buxbaum, Joseph D.
c5d8c919-2ab0-405b-9f24-1bc89b9dbf82
Glatt, Stephen J.
f8ed5b23-fc0d-4c57-a700-fbda89554592

Breen, Michael S., Tylee, Daniel S., Maihofer, Adam X., Neylan, Thomas C., Mehta, Divya, Binder, Elisabeth B., Chandler, Sharon D., Hess, Jonathan L., Kremen, William S., Risbrough, Victoria B., Woelk, Christopher H., Baker, Dewleen G., Nievergelt, Caroline M., Tsuang, Ming T., Buxbaum, Joseph D. and Glatt, Stephen J. (2018) PTSD blood transcriptome mega-analysis: shared inflammatory pathways across biological sex and modes of trauma Neuropsychopharmacology, 43, (3), pp. 469-481. (doi:10.1038/npp.2017.220).

Record type: Article

Abstract

Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.

Full text not available from this repository.

More information

Accepted/In Press date: 29 August 2017
e-pub ahead of print date: 19 September 2017
Published date: 1 February 2018

Identifiers

Local EPrints ID: 417441
URI: https://eprints.soton.ac.uk/id/eprint/417441
ISSN: 0893-133X
PURE UUID: 0d8ccf7f-47b1-4034-876e-a4b437a1d536

Catalogue record

Date deposited: 31 Jan 2018 17:30
Last modified: 31 Jan 2018 17:30

Export record

Altmetrics

Contributors

Author: Michael S. Breen
Author: Daniel S. Tylee
Author: Adam X. Maihofer
Author: Thomas C. Neylan
Author: Divya Mehta
Author: Elisabeth B. Binder
Author: Sharon D. Chandler
Author: Jonathan L. Hess
Author: William S. Kremen
Author: Victoria B. Risbrough
Author: Dewleen G. Baker
Author: Caroline M. Nievergelt
Author: Ming T. Tsuang
Author: Joseph D. Buxbaum
Author: Stephen J. Glatt

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Library staff edit
Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×