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创伤后应激障碍(PTSD)和抑郁症患者背外侧前额叶皮质中白细胞介素1A基因表达降低。

Reduced interleukin 1A gene expression in the dorsolateral prefrontal cortex of individuals with PTSD and depression.

作者信息

Morrison Filomene G, Miller Mark W, Wolf Erika J, Logue Mark W, Maniates Hannah, Kwasnik David, Cherry Jonathan D, Svirsky Sarah, Restaino Anthony, Hildebrandt Audrey, Aytan Nurgül, Stein Thor D, Alvarez Victor E, McKee Ann C, Huber Bertrand R

机构信息

National Center for PTSD at VA Boston Healthcare System, United States; Department of Psychiatry, Boston University School of Medicine, United States.

National Center for PTSD at VA Boston Healthcare System, United States; Department of Psychiatry, Boston University School of Medicine, United States; Biomedical Genetics, Boston University School of Medicine, United States; Department of Biostatistics, Boston University School of Public Health, United States.

出版信息

Neurosci Lett. 2019 Jan 23;692:204-209. doi: 10.1016/j.neulet.2018.10.027. Epub 2018 Oct 23.

Abstract

The inflammatory system has been implicated in the pathophysiology of a variety of psychiatric conditions. Individuals with PTSD, depression, and other fear- and anxiety-related disorders exhibit alterations in peripheral circulating inflammatory markers, suggesting dysregulation of the inflammatory system. The relationship between inflammation and PTSD has been investigated almost exclusively in the periphery, and has not been extensively explored in human postmortem brain tissue. Interleukins (ILs) represent a subtype of cytokines and are key signaling proteins in the immune and inflammatory systems. Based on prior research implicating IL signaling in PTSD and depression, we performed a preliminary investigation of IL gene expression in a region of the cortex involved in emotion regulation and PTSD, the dorsolateral prefrontal cortex (dlPFC), using tissue from the newly established VA National PTSD Brain Bank. Gene expression analyses were conducted on post-mortem tissue from the dlPFC from 50 donors: 13 controls, 12 PTSD cases, and 25 depressed cases. RNA was extracted from frozen dlPFC tissue, reverse transcribed to cDNA, and quantitative polymerase chain reaction (qPCR) was performed to assess gene expression of IL1A, IL1B, IL6, IL8, IL10, IL13, and IL15. We found a multiple-testing corrected significant decrease in IL1A expression in the dlPFC for PTSD and depression cases compared to controls (p < 0.005) with age at death, sex, race and RNA integrity number (RIN) included as covariates. To our knowledge this finding is the first demonstration of altered IL expression in brain tissue from deceased individuals with histories of PTSD and/or depression.

摘要

炎症系统已被认为与多种精神疾病的病理生理学有关。患有创伤后应激障碍(PTSD)、抑郁症和其他与恐惧和焦虑相关疾病的个体,其外周循环炎症标志物会发生改变,这表明炎症系统存在失调。炎症与PTSD之间的关系几乎仅在周围组织中进行了研究,而在人类死后的脑组织中尚未得到广泛探索。白细胞介素(ILs)是细胞因子的一种亚型,是免疫和炎症系统中的关键信号蛋白。基于先前将IL信号传导与PTSD和抑郁症相关联的研究,我们使用新成立的退伍军人事务部国家PTSD脑组织库的组织,对涉及情绪调节和PTSD的皮质区域——背外侧前额叶皮质(dlPFC)中的IL基因表达进行了初步研究。对来自50名捐赠者的dlPFC的死后组织进行了基因表达分析:13名对照者、12名PTSD患者和25名抑郁症患者。从冷冻的dlPFC组织中提取RNA,逆转录为cDNA,并进行定量聚合酶链反应(qPCR)以评估IL1A、IL1B、IL6、IL8、IL10、IL13和IL15的基因表达。我们发现,与对照组相比,PTSD和抑郁症患者的dlPFC中IL1A表达在进行多重检验校正后显著降低(p < 0.005),将死亡年龄、性别、种族和RNA完整性数值(RIN)作为协变量纳入分析。据我们所知,这一发现首次证明了有PTSD和/或抑郁症病史的已故个体脑组织中IL表达发生了改变。

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