Korem Nachshon, Duek Or, Xu Ke, Harpaz-Rotem Ilan, Pietrzak Robert H
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Chronic Stress (Thousand Oaks). 2021 Apr 29;5:24705470211011075. doi: 10.1177/24705470211011075. eCollection 2021 Jan-Dec.
Accumulating evidence implicates the endocannabinoid system, including variants in the cannabinoid-1 receptor gene (), in the pathophysiology of posttraumatic stress disorder (PTSD). The synonymous G1359A variant (rs1049353) in the gene has been linked to PTSD in individuals exposed to childhood abuse. In this study, the effects of the rs1049353 genotype and childhood abuse on overall PTSD symptoms, as well as PTSD symptom clusters were examined in order to examine how this interaction relates to the phenotypic expression of this disorder.
Data were analyzed from 1,372 Caucasian U.S. veterans who participated in the National Health and Resilience in Veterans Study. Multivariable analyses were conducted to evaluate the association between rs1049353 genotype, childhood abuse, and their interaction in relation to PTSD symptoms.
A significant interaction between rs1049353 genotype and childhood abuse was observed, with A allele carriers with histories of childhood abuse reporting greater severity of PTSD symptoms, most notably anxious arousal, relative to G/G homozygotes. Significant main effects of childhood abuse on overall PTSD symptoms, and re-experiencing, emotional numbing, and dysphoric arousal symptom clusters, as well as of A allele carrier status on anxious arousal symptoms were observed.
Results of this study replicate prior work and suggest that the rs1049353-by-childhood abuse interaction is particularly associated with the manifestation of anxious arousal symptoms of PTSD. Taken together, these findings underscore the importance of considering the phenotypic heterogeneity of PTSD in gene-environment studies of this multifaceted disorder.
越来越多的证据表明，包括大麻素-1受体基因（）变异在内的内源性大麻素系统与创伤后应激障碍（PTSD）的病理生理学有关。该基因中的同义G1359A变异（rs1049353）与遭受童年虐待的个体患PTSD有关。在本研究中，研究了rs1049353基因型和童年虐待对PTSD总体症状以及PTSD症状簇的影响，以探讨这种相互作用与该疾病表型表达的关系。
对1372名参与退伍军人健康与复原力研究的美国白人退伍军人的数据进行了分析。进行多变量分析以评估rs1049353基因型、童年虐待及其相互作用与PTSD症状之间的关联。
观察到rs1049353基因型与童年虐待之间存在显著的相互作用，有童年虐待史的A等位基因携带者报告的PTSD症状严重程度更高，最明显的是焦虑唤醒，相对于G/G纯合子。观察到童年虐待对PTSD总体症状、再体验、情感麻木和烦躁唤醒症状簇有显著的主效应，以及A等位基因携带者状态对焦虑唤醒症状有显著主效应。
本研究结果重复了先前的研究工作，并表明rs1049353与童年虐待的相互作用特别与PTSD焦虑唤醒症状的表现有关。综上所述，这些发现强调了在这种多方面疾病的基因-环境研究中考虑PTSD表型异质性的重要性。
