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Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: a pilot study

Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: a pilot study
Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: a pilot study
The etiology of post-traumatic stress disorder (PTSD) likely involves the interaction of numerous genes and environmental factors. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain tissues. In that context, this pilot study sought to test the following hypotheses: (1) post-trauma expression levels of a gene subset in peripheral blood would differ between Marines with and without PTSD; (2) a diagnostic biomarker panel of PTSD among high-risk individuals could be developed based on gene-expression in readily assessable peripheral blood cells; and (3) a diagnostic panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels in peripheral blood samples from 50 U.S. Marines (25 PTSD cases and 25 non-PTSD comparison subjects) were determined by microarray following their return from deployment to war-zones in Iraq or Afghanistan. The original sample was carved into training and test subsets for construction of support vector machine classifiers. The panel of peripheral blood biomarkers achieved 80% prediction accuracy in the test subset based on the expression of just two full-length transcripts (GSTM1 and GSTM2). A biomarker panel based on 20 exons attained an improved 90% accuracy in the test subset. Though further refinement and replication of these biomarker profiles are required, these preliminary results provide proof-of-principle for the diagnostic utility of blood-based mRNA-expression in PTSD among trauma-exposed individuals.
alternative splicing, mrna, peripheral blood mononuclear cells, microarray, transcriptome, trauma, diagnosis, biomarker, antioxidant, oxidative stress
0306-4530
472-494
Tylee, D.S.
9f27fff5-f183-46d3-850e-065914f2f3fd
Chandler, S.D.
5315fc01-02b4-4059-8d9b-124413b9da01
Nievergelt, C.M.
5646467c-4616-4334-98cf-9098050490b1
Liu, X.
878efcac-76c6-4ca0-8f4a-425f1e9abdac
Pazol, J.
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Woelk, C.H.
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Lohr, J.B.
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Kremen, W.S.
69e9d77a-81d6-4f79-98e1-91ce0aa2f087
Baker, D.G.
a68cca4f-3af3-4283-aad8-e1a54fe37258
Glatt, S.J.
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Tsuang, M.T.
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Tylee, D.S.
9f27fff5-f183-46d3-850e-065914f2f3fd
Chandler, S.D.
5315fc01-02b4-4059-8d9b-124413b9da01
Nievergelt, C.M.
5646467c-4616-4334-98cf-9098050490b1
Liu, X.
878efcac-76c6-4ca0-8f4a-425f1e9abdac
Pazol, J.
69e43fbc-74d9-4451-8a69-1c09bf3002dc
Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Lohr, J.B.
38f91860-591d-4296-b269-f9d276bf4e33
Kremen, W.S.
69e9d77a-81d6-4f79-98e1-91ce0aa2f087
Baker, D.G.
a68cca4f-3af3-4283-aad8-e1a54fe37258
Glatt, S.J.
277ea1bc-88a1-4a1b-823b-36430178afa7
Tsuang, M.T.
88753f4e-dfe9-4f3f-b7aa-ae8372003ddf

Tylee, D.S., Chandler, S.D., Nievergelt, C.M., Liu, X., Pazol, J., Woelk, C.H., Lohr, J.B., Kremen, W.S., Baker, D.G., Glatt, S.J. and Tsuang, M.T. (2015) Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: a pilot study. Psychoneuroendocrinology, 51, 472-494. (doi:10.1016/j.psyneuen.2014.09.024).

Record type: Article

Abstract

The etiology of post-traumatic stress disorder (PTSD) likely involves the interaction of numerous genes and environmental factors. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain tissues. In that context, this pilot study sought to test the following hypotheses: (1) post-trauma expression levels of a gene subset in peripheral blood would differ between Marines with and without PTSD; (2) a diagnostic biomarker panel of PTSD among high-risk individuals could be developed based on gene-expression in readily assessable peripheral blood cells; and (3) a diagnostic panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels in peripheral blood samples from 50 U.S. Marines (25 PTSD cases and 25 non-PTSD comparison subjects) were determined by microarray following their return from deployment to war-zones in Iraq or Afghanistan. The original sample was carved into training and test subsets for construction of support vector machine classifiers. The panel of peripheral blood biomarkers achieved 80% prediction accuracy in the test subset based on the expression of just two full-length transcripts (GSTM1 and GSTM2). A biomarker panel based on 20 exons attained an improved 90% accuracy in the test subset. Though further refinement and replication of these biomarker profiles are required, these preliminary results provide proof-of-principle for the diagnostic utility of blood-based mRNA-expression in PTSD among trauma-exposed individuals.

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More information

Accepted/In Press date: 22 September 2014
e-pub ahead of print date: 30 September 2014
Published date: January 2015
Keywords: alternative splicing, mrna, peripheral blood mononuclear cells, microarray, transcriptome, trauma, diagnosis, biomarker, antioxidant, oxidative stress
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 379206
URI: https://eprints.soton.ac.uk/id/eprint/379206
ISSN: 0306-4530
PURE UUID: 058bb2a8-1c16-404c-b19a-181a8d6d0c8e

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Date deposited: 18 Jul 2015 14:36
Last modified: 15 Jul 2019 21:12

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Contributors

Author: D.S. Tylee
Author: S.D. Chandler
Author: C.M. Nievergelt
Author: X. Liu
Author: J. Pazol
Author: C.H. Woelk
Author: J.B. Lohr
Author: W.S. Kremen
Author: D.G. Baker
Author: S.J. Glatt
Author: M.T. Tsuang

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