Dahrendorff Jan, Wani Agaz, Keller Thomas, Armstrong Don, Qu Annie, Wildman Derek E, Valero Maria Carmen, Koenen Karestan C, Aiello Allison E, Uddin Monica
Genomics Program, College of Public Health, University of South Florida, Tampa, FL.
Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL.
Hum Biol. 2023 Winter;95(1):33-47. doi: 10.1353/hub.2017.a935047.
Post-traumatic stress disorder (PTSD) is a common and debilitating psychiatric disorder that may occur in individuals exposed to traumatic events such as accidents, interpersonal violence, war, combat, or natural disasters. Additionally, PTSD has been implicated in the development of a variety of chronic conditions including cardiovascular and metabolic diseases, suggesting that the biological alterations associated with the disorder can manifest themselves as chronic diseases in those suffering from PTSD. The biological underpinnings of the disorder are not well understood. Gene expression studies can illuminate the complex physiology of PTSD reflecting the embodiment of trauma, i.e., the process in which traumatic experiences in our social environments could potentially be manifested in our body by genomic mechanisms. To date, gene expression studies that examine the whole transcriptome are scarce and limited to single-timepoint assessments. Here we applied a transcriptome-wide gene expression screen with RNA-sequencing to whole blood samples from predominantly African-American participants in a community-dwelling setting to elucidate the gene expression signatures associated with the development of PTSD. The study participants (N=72, of whom 21 eventually developed PTSD) are a trauma-exposed subsample of participants enrolled in a longitudinal and prospective cohort study of adults living in Detroit, Michigan. PTSD was assessed in a structured telephone interview and whole blood samples were taken both before and after trauma exposure. We found 45 differentially expressed genes associated with PTSD development with an estimated log2 fold change > 1.5 at a nominal p-value (pPAX6, TSPAN7, PXDN, VWC2, SULF1, and NFATC4 were also ubiquitously expressed in all brain regions. Longitudinal sampling provides a promising mean to elucidate the pathophysiology underlying the embodiment of trauma.
创伤后应激障碍(PTSD)是一种常见且使人衰弱的精神障碍,可能发生在经历过诸如事故、人际暴力、战争、战斗或自然灾害等创伤性事件的个体身上。此外,PTSD与包括心血管和代谢疾病在内的多种慢性疾病的发生有关,这表明与该障碍相关的生物学改变可在PTSD患者身上表现为慢性疾病。该障碍的生物学基础尚未完全明确。基因表达研究可以阐明PTSD复杂的生理学机制,反映创伤的体现,即我们社会环境中的创伤经历可能通过基因组机制在我们身体中表现出来的过程。迄今为止,检查全转录组的基因表达研究很少,且仅限于单时间点评估。在这里,我们对社区居住环境中主要为非裔美国参与者的全血样本进行了全转录组范围的基因表达筛选,以阐明与PTSD发展相关的基因表达特征。研究参与者(N = 72,其中21人最终患上PTSD)是参与密歇根州底特律市成年人纵向前瞻性队列研究的受创伤暴露子样本。通过结构化电话访谈评估PTSD,并在创伤暴露前后采集全血样本。我们发现45个与PTSD发展相关的差异表达基因,在名义p值(pPAX6、TSPAN7、PXDN、VWC2、SULF1和NFATC4在所有脑区也均有广泛表达。纵向采样为阐明创伤体现背后的病理生理学提供了一个有前景的方法。