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

Authors

  • Stephen J. Glatt,

    Corresponding author
    1. Psychiatric Genetic Epidemiology and Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
    • SUNY Upstate Medical University, 750 East Adams Street Syracuse, Syracuse, NY 13210.
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  • Daniel S. Tylee,

    1. Psychiatric Genetic Epidemiology and Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
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  • Sharon D. Chandler,

    1. Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
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  • Joel Pazol,

    1. Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
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  • Caroline M. Nievergelt,

    1. VA Center of Excellence for Stress and Mental Health, San Diego, California
    2. Veterans Affairs San Diego Healthcare System, San Diego, California
    3. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • Christopher H. Woelk,

    1. Veterans Affairs San Diego Healthcare System, San Diego, California
    2. Department of Medicine, University of California, San Diego, La Jolla, California
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  • Dewleen G. Baker,

    1. VA Center of Excellence for Stress and Mental Health, San Diego, California
    2. Veterans Affairs San Diego Healthcare System, San Diego, California
    3. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • James B. Lohr,

    1. VA Center of Excellence for Stress and Mental Health, San Diego, California
    2. Veterans Affairs San Diego Healthcare System, San Diego, California
    3. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • William S. Kremen,

    1. Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
    2. VA Center of Excellence for Stress and Mental Health, San Diego, California
    3. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • Brett T. Litz,

    1. Veterans Affairs Boston Healthcare System, Boston, Massachusetts
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  • Ming T. Tsuang,

    1. Department of Psychiatry, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
    2. VA Center of Excellence for Stress and Mental Health, San Diego, California
    3. Veterans Affairs San Diego Healthcare System, San Diego, California
    4. Department of Psychiatry, University of California, San Diego, La Jolla, California
    5. Boston University, Boston, Massachusetts
    6. Institute of Genomic Medicine, University of California, San Diego, La Jolla, California
    7. Department of Epidemiology, Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard School of Public Health, Boston, Massachusetts
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  • Marine Resiliency Study Investigators


  • How to cite this article: Glatt SJ, Tylee DS, Chandler SD, Pazol J, Nievergelt CM, Woelk CH, Baker DG, Lohr JB, Kremen WS, Litz BT, Tsuang MT, Marine Resiliency Study Investigators. 2013. Blood-Based Gene-Expression Predictors of PTSD Risk and Resilience Among Deployed Marines: A Pilot Study. Am J Med Genet Part B 162B:313–326.

  • Stephen J. Glatt and Daniel S. Tylee contributed equally to this work.

  • §

    The authors report no conflicts of interest.

  • The Marine Resiliency Study Investigators include William P. Nash (Boston VA Research Institute); Mark A. Geyer (University of California-San Diego and VA Center of Excellence for Stress and Mental Health); Paul S. Hammer (Defense Centers of Excellence for Stress and Mental Health and Traumatic Brain Injury, Arlington, Virginia); Gerald E. Larsen (Naval Health Research Center, San Diego, California); Daniel T. O'Connor (University of California-San Diego); Victoria B. Risbrough (VA Center of Excellence for Stress and Mental Health San Diego and University of California-San Diego); Nicholas J. Schork (Scripps Translational Science Institute, La Jolla, California); Jennifer J. Vasterling (Veterans Affairs Boston Healthcare System, Boston, Massachusetts and Boston University); and Jennifer A. Webb-Murphy (Naval Center for Combat & Operational Stress Control, San Diego, California).

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. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.

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