Gene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD.
Gene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD.
复制标题
DOI：
10.1016/j.ynstr.2021.100398
复制
发表时间：
2021-11
影响因子：
5
通讯作者：
Miller MW
中科院分区：
文献类型：
--
作者：
Logue MW;Zhou Z;Morrison FG;Wolf EJ;Daskalakis NP;Chatzinakos C;Georgiadis F;Labadorf AT;Girgenti MJ;Young KA;Williamson DE;Zhao X;Grenier JG;Traumatic Stress Brain Research Group;Huber BR;Miller MW
评估神经影像学、基因预测基因表达和 PTSD 临床前遗传模型的研究已经确定了大脑前额皮质 (PFC) 中与 PTSD 相关的异常，特别是背外侧和腹内侧 PFC（dlPFC 和 vmPFC）。在这项研究中，使用来自 VA 国家 PTSD 脑库的组织，通过 RNA 测序来检查有或没有抑郁症 PTSD 病史的捐赠者 (dlPFC n = 38, vmPFC n = 35)、无 PTSD 抑郁症病例 (n = 32) 和无精神病理学对照 (dlPFC n = 24, vmPFC) 的 dlPFC 和 vmPFC 中的基因表达。 n = 20)。分析将 PTSD 病例与对照进行比较。后续分析将抑郁症病例与对照组进行了对比。经过严格的多重检验校正后，21个基因在PTSD中差异表达。鉴定出与学习和记忆（FOS、NR4A1）、免疫调节（CFH、KPNA1）和髓鞘形成（MBP、MOBP、ERMN）相关的 PTSD 相关基因。 PTSD 相关基因与抑郁症相关基因部分重叠。共表达网络分析确定了两个大脑区域中富含免疫相关基因的 PTSD 相关网络。然而，免疫相关基因和关联模式是不同的。在候选基因分析中，免疫基因 IL1B 与 PTSD 显着相关，并且是两个区域中 PTSD 相关基因的上游调节因子。有证据表明 dlPFC 关联在最近的一项独立队列中得到复制，并且两项研究中重要基因的 dlPFC PTSD 效应大小之间存在很强的相关性（r = 0.66，p < 2.2 × 10−16）。总之，本研究确定了几个新的 PTSD 相关基因和大脑区域特定的 PTSD 相关免疫相关网络。
Studies evaluating neuroimaging, genetically predicted gene expression, and pre-clinical genetic models of PTSD, have identified PTSD-related abnormalities in the prefrontal cortex (PFC) of the brain, particularly in dorsolateral and ventromedial PFC (dlPFC and vmPFC). In this study, RNA sequencing was used to examine gene expression in the dlPFC and vmPFC using tissue from the VA National PTSD Brain Bank in donors with histories of PTSD with or without depression (dlPFC n = 38, vmPFC n = 35), depression cases without PTSD (n = 32), and psychopathology-free controls (dlPFC n = 24, vmPFC n = 20). Analyses compared PTSD cases to controls. Follow-up analyses contrasted depression cases to controls. Twenty-one genes were differentially expressed in PTSD after strict multiple testing correction. PTSD-associated genes with roles in learning and memory (FOS, NR4A1), immune regulation (CFH, KPNA1) and myelination (MBP, MOBP, ERMN) were identified. PTSD-associated genes partially overlapped depression-associated genes. Co-expression network analyses identified PTSD-associated networks enriched for immune-related genes across the two brain regions. However, the immune-related genes and association patterns were distinct. The immune gene IL1B was significantly associated with PTSD in candidate-gene analysis and was an upstream regulator of PTSD-associated genes in both regions. There was evidence of replication of dlPFC associations in an independent cohort from a recent study, and a strong correlation between the dlPFC PTSD effect sizes for significant genes in the two studies (r = 0.66, p < 2.2 × 10−16). In conclusion, this study identified several novel PTSD-associated genes and brain region specific PTSD-associated immune-related networks.
登录
查看更多内容
影响因子：
2.5
作者：
BULLITT, E
通讯作者：
BULLITT, E
影响因子：
7.7
作者：
Bonnefil, Valentina;Dietz, Karen;Liu, Jia
通讯作者：
Liu, Jia
影响因子：
4.7
作者：
DiSabato DJ;Quan N;Godbout JP
通讯作者：
Godbout JP
影响因子：
7.3
作者：
Bellavance MA;Rivest S
通讯作者：
Rivest S
影响因子：
3
作者：
Chao LL;Tosun D;Woodward SH;Kaufer D;Neylan TC
通讯作者：
Neylan TC