Wolf Erika J, Rasmusson Ann M, Mitchell Karen S, Logue Mark W, Baldwin Clinton T, Miller Mark W
National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts; Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts.
Depress Anxiety. 2014 Apr;31(4):352-60. doi: 10.1002/da.22260. Epub 2014 Mar 27.
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.
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.
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.
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.
近期研究表明,创伤后应激障碍(PTSD)患者的一个亚组表现出明显的解离症状,如现实解体和人格解体所定义的那样。《精神疾病诊断与统计手册》第5版(DSM - 5)列出的诊断标准中增加了PTSD的解离亚型,以涵盖PTSD的这种表现形式。本研究采用全基因组方法,检测与定义PTSD解离亚型症状相关的基因多态性。
样本包括484名非西班牙裔白人创伤暴露退伍军人及其伴侣,他们通过结构化临床访谈接受了终生PTSD和解离评估。PTSD的患病率为60.5%。从250万个单核苷酸多态性(SNP)阵列中获取全基因组的SNP。
10个SNP显示出与解离有提示性关联(P < 10⁻⁵)。没有SNP达到全基因组显著性标准(P < 5×10⁻⁸)。峰值SNP是rs263232(β = 1.4,P = 6.12×10⁻⁷),位于腺苷酸环化酶8(ADCY8)基因;提示范围内的第二个SNP是rs71534169(β = 1.63,P = 3.79×10⁻⁶),位于二肽基肽酶6(DPP6)基因。
ADCY8对长期增强和突触可塑性至关重要,并与恐惧相关学习、记忆及长期记忆巩固有关。DPP6对突触整合和兴奋至关重要。这些基因可能对解离现象背后的基本感觉整合和认知过程产生影响。