A GENOME-WIDE ASSOCIATION STUDY OF CLINICAL SYMPTOMS OF DISSOCIATION IN A TRAUMA-EXPOSED SAMPLE: Research Article: Genetics of Dissociation
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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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Recent research points to possible links between dissociative symptoms in PTSD and genes related to learning and memory function.
“There are currently no DID-specific molecular genetic studies; however, recent research points to some possible links between dissociative symptoms in PTSD and genes related to learning and memory function [60,61].”
From Treatment of dissociative identity disorder: leveraging neurobiology to optimize success (2024) · cites this paper as [60]
SNPs within the AC8 gene are associated with posttraumatic stress disorder.
“AC8 has a demonstrated role in stress-induced behaviors and anxiety in mouse models, consistent with human studies that have identified SNPs within the AC8 gene that are associated with bipolar disorder (207, 208), posttraumatic stress disorder (209), and alcoholism comorbid with major depressive disorder (168).”
From Physiological roles of mammalian transmembrane adenylyl cyclase isoforms (2022) · cites this paper as [209]
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- Authors
- Wolf, E. J., Rasmusson, A. M., Mitchell, K. S., Logue, M. W., Baldwin, C. T., & Miller, M. W.
- Affiliations
- Boston University (US)
- Corresponding author
- Wolf, Erika J.
- Miller, Mark W.
- Venue
- Depression and Anxiety
- Publisher
- Wiley
- Published
- 2014-03-27
- Volume
- 31
- Issue
- 4
- Pages
- 352-360
- ISSN
- 1091-4269 (ISSN-L)
- PMC
- PMC3984628
- OpenAlex
- W2129911738
- Cited by
- 75
- References
- 68
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 7 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 7 · 2014: 1
- FWCI
- 9.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (CDA-2-067-10S, I01 BX002150, I01 CX000431)
- National Institute of Mental Health (R01MH079806, K01MH093750)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- dissociation, derealization, depersonalization, genetic polymorphism, single nucleotide polymorphisms, ADCY8, DPP6, synaptic plasticity, fear memory consolidation, sensory integration
- MeSH terms
- Adenylyl Cyclases, Adult, Aged, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Dissociative Disorders, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Severity of Illness Index, Stress Disorders, Post-Traumatic, Veterans, Potassium Channels, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Young Adult
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