美国耶鲁大学公共卫生学院Hongyu Zhao、John H. Krystal等合作揭示了创伤后应激障碍（PTSD）的人脑转录组学组织。相关论文于2020年12月21日发表于《自然-神经科学》杂志。
PTSD患者死后组织的四个前额叶皮层亚区域的差异基因表达和网络分析表明，转录组图谱得到了广泛的重塑。与PTSD相关的最重要的基因网络中存在高度相关中间神经元转录物的下调。该数据集与最大的PTSD基因组范围关联研究的基因型数据整合后，确定神经元突触间基因ELFN1赋予PTSD重大的遗传能力。
他们还确定了明显的转录组性二态性，可能导致女性更高的PTSD发生率。与相匹配的重度抑郁症队列比较表明，尽管合并症高，但PTSD患者和重度抑郁症患者的分子谱存在显著差异。他们的分析为额叶皮层内的基因组网络提供了一致的系统级证据，这些基因组网络有助于人类PTSD的病理生理。
据介绍，PTSD的神经生物学相关性进行了广泛研究，但对其分子决定因素知之甚少。
附：英文原文
Title: Transcriptomic organization of the human brain in post-traumatic stress disorder
Author: Matthew J. Girgenti, Jiawei Wang, Dingjue Ji, Dianne A. Cruz, Murray B. Stein, Joel Gelernter, Keith A. Young, Bertrand R. Huber, Douglas E. Williamson, Matthew J. Friedman, John H. Krystal, Hongyu Zhao, Ronald S. Duman
Issue&Volume: 2020-12-21
Abstract: Despite extensive study of the neurobiological correlates of post-traumatic stress disorder (PTSD), little is known about its molecular determinants. Here, differential gene expression and network analyses of four prefrontal cortex subregions from postmortem tissue of people with PTSD demonstrate extensive remodeling of the transcriptomic landscape. A highly connected downregulated set of interneuron transcripts is present in the most significant gene network associated with PTSD. Integration of this dataset with genotype data from the largest PTSD genome-wide association study identified the interneuron synaptic gene ELFN1 as conferring significant genetic liability for PTSD. We also identified marked transcriptomic sexual dimorphism that could contribute to higher rates of PTSD in women. Comparison with a matched major depressive disorder cohort revealed significant divergence between the molecular profiles of individuals with PTSD and major depressive disorder despite their high comorbidity. Our analysis provides convergent systems-level evidence of genomic networks within the prefrontal cortex that contribute to the pathophysiology of PTSD in humans. A transcriptome-wide characterization of the molecular pathology of post-traumatic stress disorder (PTSD) postmortem brains provides a comprehensive resource for mechanistic insight and therapeutic development.
DOI: 10.1038/s41593-020-00748-7
Source: https://www.nature.com/articles/s41593-020-00748-7
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
