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.

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叶皮层 (PFC) 中与 PTSD 相关的异常，特别是在背外侧和腹内侧 PFC (dlPFC 和 vmPFC)。在这项研究中，RNA 测序用于检查 dlPFC 和 vmPFC 中的基因表达，使用来自 VA 国家 PTSD 脑库的组织在有或没有抑郁症（dlPFC n = 38，vmPFC n = 35）、抑郁症病例的 PTSD 病史的供体中没有 PTSD (n = 32) 和无精神病理学对照 (dlPFC n = 24, vmPFC n = 20)。分析将 PTSD 病例与对照组进行了比较。后续分析将抑郁症病例与对照组进行了对比。经过严格的多重测试校正后，21个基因在PTSD中出现差异表达。在学习和记忆中发挥作用的 PTSD 相关基因 (FOS、NR4A1）、免疫调节（CFH、KPNA1）和髓鞘形成（MBP、MOBP、ERMN）被鉴定。创伤后应激障碍相关基因与抑郁相关基因部分重叠。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。免疫基因IL1B在候选基因分析中与 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。在最近的一项研究中，有证据表明在独立队列中复制了 dlPFC 关联，并且在两项研究中显着基因的 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，这项研究确定了几个新的 PTSD 相关基因和脑区特异性 PTSD 相关免疫相关网络。