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A GENOME-WIDE ASSOCIATION STUDY OF CLINICAL SYMPTOMS OF DISSOCIATION IN A TRAUMA-EXPOSED SAMPLE

Authors

  • Erika J. Wolf 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: Erika J. Wolf and Mark W. Miller, National Center for PTSD, VA Boston Healthcare System (116B-2), 150 South Huntington Avenue, Boston, MA 02130. E-mail: erika.wolf@va.gov; mark.miller5@va.gov

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  • Ann M. Rasmusson M.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, Massachusetts
    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, 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: Erika J. Wolf and Mark W. Miller, National Center for PTSD, VA Boston Healthcare System (116B-2), 150 South Huntington Avenue, Boston, MA 02130. E-mail: erika.wolf@va.gov; mark.miller5@va.gov

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  • Contract grant sponsor: National Institute on Mental Health; Contract grant number: RO1 MH079806; Contract grant sponsor: VA CSR&D Merit Award; Contract grant number: K01MH093750; Contract grant sponsor: VA CSR&D Career Development Award.

Abstract

Background

Recent work suggests that a subset of individuals with posttraumatic stress disorder (PTSD) exhibit marked dissociative symptoms, as defined by derealization and depersonalization. A dissociative subtype of PTSD was added to the diagnostic criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) to capture this presentation of PTSD. This study examined genetic polymorphisms for association with the symptoms that define the dissociative subtype of PTSD using a genome-wide approach.

Methods

The sample comprised 484 White, non-Hispanic, trauma-exposed veterans and their partners who were assessed for lifetime PTSD and dissociation using a structured clinical interview. The prevalence of PTSD was 60.5%. Single-nucleotide polymorphisms (SNPs) from across the genome were obtained from a 2.5 million SNP array.

Results

Ten SNPs evidenced suggestive association with dissociation (P < 10−5). No SNPs met genome-wide significance criteria (P < 5 × 10−8). The peak SNP was rs263232 (β = 1.4, P = 6.12 × 10−7), located in the adenylyl cyclase 8 (ADCY8) gene; a second SNP in the suggestive range was rs71534169 (β = 1.63, P = 3.79 × 10−6), located in the dipeptidyl-peptidase 6 (DPP6) gene.

Conclusions

ADCY8 is integral for long-term potentiation and synaptic plasticity and is implicated in fear-related learning and memory and long-term memory consolidation. DPP6 is critical for synaptic integration and excitation. These genes may exert effects on basic sensory integration and cognitive processes that underlie dissociative phenomena.

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