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CORTICOTROPIN RELEASING HORMONE RECEPTOR 2 (CRHR-2) GENE IS ASSOCIATED WITH DECREASED RISK AND SEVERITY OF POSTTRAUMATIC STRESS DISORDER IN WOMEN

Authors

  • Erika J. Wolf Ph.D.,

    1. National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts
    2. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts
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  • Karen S. Mitchell Ph.D.,

    1. National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts
    2. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts
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  • Mark W. Logue Ph.D.,

    1. Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
    2. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
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  • Clinton T. Baldwin Ph.D.,

    1. Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
    2. Center for Human Genetics, Boston University School of Medicine, Boston, Massachusetts
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  • Annemarie F. Reardon Ph.D.,

    1. National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts
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  • Donald E. Humphries Ph.D.,

    1. Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, Massachusetts
    2. Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
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  • Mark W. Miller Ph.D.

    Corresponding author
    1. National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts
    2. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts
    • Correspondence to: Mark W. Miller, National Center for PTSD, VA Boston Healthcare System (116B-2), 150 South Huntington Avenue, Boston, MA 02130. E-mail: mark.miller5@va.gov

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  • Contract grant number: RO1 MH079806; Contract grant number: K01MH093750.

Abstract

Background

The corticotropin releasing hormone (CRH) system has been implicated in a variety of anxiety and mood-based symptoms and disorders. CRH receptor-2 (CRHR-2) plays a role in attenuating biological responses to stressful life events and trauma, making the CRHR-2 gene a strong candidate to study in relationship to PTSD.

Methods

The sample was 491 trauma-exposed white non-Hispanic veterans and their cohabitating intimate partners assessed via structured interview for lifetime DSM-IV PTSD; just over 60% met criteria for the disorder. Thirty-one single nucleotide polymorphisms (SNPs) in and near CRHR-2, obtained from an array of 2.5 million markers, were tested for association with PTSD diagnosis and symptom severity in the whole sample and in men and women separately.

Results

Ten SNPs showed nominally significant evidence of association with PTSD in the full sample and two SNPs (rs8192496 and rs2190242) were significant after permutation-based multiple testing correction (uncorrected ps = .0004 and .0005, odds ratios = .60 and .58, respectively). Analyses stratified by sex revealed that the effect was specific to women, who comprised 35% of the sample (uncorrected ps = .0003 and .0002, odds ratios = .41 and .35, respectively). Two additional SNPs (rs2267715 and rs2284218) also showed significant association with PTSD in women (both uncorrected ps = .001, both odds ratios = .48).

Conclusions

Results suggest that CRHR-2 variants may affect risk for PTSD in women by attenuating the stress response and reducing symptoms of the disorder.

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