研究人员对创伤后应激障碍（PTSD）和重度抑郁障碍（MDD）的大脑多区域、多组学研究包括杏仁核中央核、海马齿状回和内侧前额叶皮层（mPFC）。mPFC中的基因和外显子携带的疾病信号在两个独立队列中得到了复制。通路指向免疫功能、神经元和突触调节以及应激激素。多组因子和基因网络分析提供了潜在的基因组结构。
背外侧PFC单核RNA测序显示了神经元和非神经元细胞类型的失调（压力相关）信号。研究人员对超过50000名英国生物库参与者的脑血交叉点进行了分析，并对PTSD和MDD全基因组关联研究的结果进行了精细映射，以区分风险和疾病过程。这些数据表明，这两种疾病的分子病理既有相同之处，也有不同之处，并提出了潜在的治疗目标和生物标志物。
据悉，应激相关障碍的分子病理学仍然难以捉摸。
附：英文原文
Title: Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood
Author: Nikolaos P. Daskalakis, Artemis Iatrou, Chris Chatzinakos, Aarti Jajoo, Clara Snijders, Dennis Wylie, Christopher P. DiPietro, Ioulia Tsatsani, Chia-Yen Chen, Cameron D. Pernia, Marina Soliva-Estruch, Dhivya Arasappan, Rahul A. Bharadwaj, Leonardo Collado-Torres, Stefan Wuchty, Victor E. Alvarez, Eric B. Dammer, Amy Deep-Soboslay, Duc M. Duong, Nick Eagles, Bertrand R. Huber, Louise Huuki, Vincent L. Holstein, Mark W. Logue, Justina F. Lugenbühl, Adam X. Maihofer, Mark W. Miller, Caroline M. Nievergelt, Geo Pertea, Deanna Ross, Mohammad S. E. Sendi, Benjamin B. Sun, Ran Tao, James Tooke, Erika J. Wolf, Zane Zeier, PTSD Working Group of Psychiatric Genomics Consortium**, Sabina Berretta, Frances A. Champagne, Thomas Hyde, Nicholas T. Seyfried, Joo Heon Shin, Daniel R. Weinberger, Charles B. Nemeroff, Joel E. Kleinman, Kerry J. Ressler
Issue&Volume: 2024-05-24
Abstract: The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.
DOI: adh3707
Source: https://www.science.org/doi/10.1126/science.adh3707