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Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines. A pilot study

Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines. A pilot study
Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines. A pilot study
Susceptibility to PTSD is determined by both genes and environment. 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. Therefore, our objectives were to test the following hypotheses: (1) pre-trauma expression levels of a gene subset (particularly immune-system genes) in peripheral blood would differ between trauma-exposed Marines who later developed PTSD and those who did not; (2) a predictive biomarker panel of the eventual emergence of PTSD among high-risk individuals could be developed based on gene expression in readily assessable peripheral blood cells; and (3) a predictive 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 were assayed in peripheral blood samples from 50 U.S. Marines (25 eventual PTSD cases and 25 non-PTSD comparison subjects) prior to their deployment overseas to war-zones in Iraq or Afghanistan. The panel of biomarkers dysregulated in peripheral blood cells of eventual PTSD cases prior to deployment was significantly enriched for immune genes, achieved 70% prediction accuracy in an independent sample based on the expression of 23 full-length transcripts, and attained 80% accuracy in an independent sample based on the expression of one exon from each of five genes. If the observed profiles of pre-deployment mRNA-expression in eventual PTSD cases can be further refined and replicated, they could suggest avenues for early intervention and prevention among individuals at high risk for trauma exposure.
alternative splicing, mRNA, peripheral blood mononuclear cells, transcriptome, trauma
1552-4841
Glatt, Stephen G.
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Tylee, Daniel S.
9bcfee5d-4cb2-41ae-a3d2-0d4e7f7a81b1
Chandler, Sharon D.
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Pazol, Joel
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Nievergelt, Caroline M.
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Woelk, Christopher H.
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Baker, Dewleen G.
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Lohr, James B.
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Kremen, William S.
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Litz, Brett T.
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Ming, T. Tsuang
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Glatt, Stephen G.
48ace184-095b-401e-8442-fdbe5544557d
Tylee, Daniel S.
9bcfee5d-4cb2-41ae-a3d2-0d4e7f7a81b1
Chandler, Sharon D.
58f659ec-a938-4b98-a759-e4a72445dda8
Pazol, Joel
8264fa07-2b69-4a54-8e8c-e6a9ce225398
Nievergelt, Caroline M.
9308faea-edfd-4f38-b744-9698e32d1341
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Baker, Dewleen G.
a39cdf15-cb1a-4dfa-b3ff-ee9f5b2ae447
Lohr, James B.
c7da1778-4178-4630-ae3f-5a74f60bea1a
Kremen, William S.
32f31531-e6d2-4ee3-942c-ce67dad63d70
Litz, Brett T.
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Ming, T. Tsuang
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Glatt, Stephen G., Tylee, Daniel S., Chandler, Sharon D., Pazol, Joel, Nievergelt, Caroline M., Woelk, Christopher H., Baker, Dewleen G., Lohr, James B., Kremen, William S., Litz, Brett T. and Ming, T. Tsuang (2013) Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines. A pilot study. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. (doi:10.1002/ajmg.b.32167). (PMID:23650250)

Record type: Article

Abstract

Susceptibility to PTSD is determined by both genes and environment. 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. Therefore, our objectives were to test the following hypotheses: (1) pre-trauma expression levels of a gene subset (particularly immune-system genes) in peripheral blood would differ between trauma-exposed Marines who later developed PTSD and those who did not; (2) a predictive biomarker panel of the eventual emergence of PTSD among high-risk individuals could be developed based on gene expression in readily assessable peripheral blood cells; and (3) a predictive 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 were assayed in peripheral blood samples from 50 U.S. Marines (25 eventual PTSD cases and 25 non-PTSD comparison subjects) prior to their deployment overseas to war-zones in Iraq or Afghanistan. The panel of biomarkers dysregulated in peripheral blood cells of eventual PTSD cases prior to deployment was significantly enriched for immune genes, achieved 70% prediction accuracy in an independent sample based on the expression of 23 full-length transcripts, and attained 80% accuracy in an independent sample based on the expression of one exon from each of five genes. If the observed profiles of pre-deployment mRNA-expression in eventual PTSD cases can be further refined and replicated, they could suggest avenues for early intervention and prevention among individuals at high risk for trauma exposure.

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More information

e-pub ahead of print date: May 2013
Keywords: alternative splicing, mRNA, peripheral blood mononuclear cells, transcriptome, trauma
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 352909
URI: http://eprints.soton.ac.uk/id/eprint/352909
ISSN: 1552-4841
PURE UUID: 63bbabdd-9368-4815-96a7-4f9bce43938e

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Date deposited: 23 May 2013 09:31
Last modified: 14 Mar 2024 13:58

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Contributors

Author: Stephen G. Glatt
Author: Daniel S. Tylee
Author: Sharon D. Chandler
Author: Joel Pazol
Author: Caroline M. Nievergelt
Author: Christopher H. Woelk
Author: Dewleen G. Baker
Author: James B. Lohr
Author: William S. Kremen
Author: Brett T. Litz
Author: T. Tsuang Ming

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