Objective:

Posttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease that is highly comorbid with major depressive disorder (MDD) and bipolar disorder. The overlap in symptoms is hypothesized to stem from partially shared genetics and underlying neurobiological mechanisms. To delineate conservation between transcriptional patterns across PTSD and MDD, the authors examined gene expression in the human cortex and amygdala in these disorders.

Methods:

RNA sequencing was performed in the postmortem brain of two prefrontal cortex regions and two amygdala regions from donors diagnosed with PTSD (N=107) or MDD (N=109) as well as from neurotypical donors (N=109).

Results:

The authors identified a limited number of differentially expressed genes (DEGs) specific to PTSD, with nearly all mapping to cortical versus amygdala regions. PTSD-specific DEGs were enriched in gene sets associated with downregulated immune-related pathways and microglia as well as with subpopulations of GABAergic inhibitory neurons. While a greater number of DEGs associated with MDD were identified, most overlapped with PTSD, and only a few were MDD specific. The authors used weighted gene coexpression network analysis as an orthogonal approach to confirm the observed cellular and molecular associations.

Conclusions:

These findings provide supporting evidence for involvement of decreased immune signaling and neuroinflammation in MDD and PTSD pathophysiology, and extend evidence that GABAergic neurons have functional significance in PTSD.

中文翻译：

---

解码 PTSD 和抑郁症中皮质-杏仁核回路的共享转录组特征与不同转录组特征

客观的：

创伤后应激障碍（PTSD）是一种使人衰弱的神经精神疾病，与重度抑郁症（MDD）和双相情感障碍高度共存。假设症状的重叠源于部分共享的遗传学和潜在的神经生物学机制。为了描绘 PTSD 和 MDD 转录模式之间的保守性，作者检查了这些疾病中人类皮质和杏仁核的基因表达。

方法：

对诊断为 PTSD (N=107) 或 MDD (N=109) 以及神经典型供体 (N=109) 的捐献者死后大脑的两个前额皮质区域和两个杏仁核区域进行 RNA 测序。

结果：

作者确定了有限数量的 PTSD 特异性差异表达基因 (DEG)，几乎所有基因都映射到皮质和杏仁核区域。PTSD 特异性 DEG 富含与下调的免疫相关途径和小胶质细胞以及 GABA 能抑制神经元亚群相关的基因集。虽然发现了更多与 MDD 相关的 DEG，但大多数与 PTSD 重叠，并且只有少数是 MDD 特有的。作者使用加权基因共表达网络分析作为正交方法来确认观察到的细胞和分子关联。

结论：

这些发现为 MDD 和 PTSD 病理生理学中免疫信号传导和神经炎症减少的参与提供了支持证据，并进一步证明 GABA 能神经元在 PTSD 中具有功能意义。