The Brain Body Institute, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada.
McMaster Immunology Research Centre, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2022 Oct 7;17(10):e0275864. doi: 10.1371/journal.pone.0275864. eCollection 2022.
Asthma, an inflammatory disorder of the airways, is one of the most common chronic illnesses worldwide and is associated with significant morbidity. There is growing recognition of an association between asthma and mood disorders including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). Although there are several hypotheses regarding the relationship between asthma and mental health, there is little understanding of underlying mechanisms and causality. In the current study we utilized publicly available datasets of human blood mRNA collected from patients with severe and moderate asthma, MDD, and PTSD. We performed differential expression (DE) analysis and Gene Set Enrichment Analysis (GSEA) on diseased subjects against the healthy subjects from their respective datasets, compared the results between diseases, and validated DE genes and gene sets with 4 more independent datasets. Our analysis revealed that commonalities in blood transcriptomic changes were only found between the severe form of asthma and mood disorders. Gene expression commonly regulated in PTSD and severe asthma, included ORMDL3 a gene known to be associated with asthma risk and STX8, which is involved in TrkA signaling. We also identified several pathways commonly regulated to both MDD and severe asthma. This study reveals gene and pathway regulation that potentially drives the comorbidity between severe asthma, PTSD, and MDD and may serve as foci for future research aimed at gaining a better understanding of both the relationship between asthma and PTSD, and the pathophysiology of the individual disorders.
哮喘是一种气道炎症性疾病，是全球最常见的慢性疾病之一，与显著的发病率相关。人们越来越认识到哮喘与情绪障碍之间存在关联，包括创伤后应激障碍（PTSD）和重度抑郁症（MDD）。尽管关于哮喘与心理健康之间的关系存在多种假说，但对潜在机制和因果关系的理解甚少。在本研究中，我们利用了从重度和中度哮喘、MDD 和 PTSD 患者中收集的人类血液 mRNA 的公开可用数据集。我们对疾病患者与各自数据集的健康对照进行了差异表达（DE）分析和基因集富集分析（GSEA），比较了疾病之间的结果，并使用 4 个额外的独立数据集验证了 DE 基因和基因集。我们的分析表明，仅在重度哮喘和情绪障碍之间发现了血液转录组变化的共性。在 PTSD 和重度哮喘中共同调节的基因表达，包括已知与哮喘风险相关的 ORMDL3 基因和参与 TrkA 信号的 STX8 基因。我们还鉴定了几个共同调节 MDD 和重度哮喘的途径。这项研究揭示了潜在驱动重度哮喘、PTSD 和 MDD 共病的基因和途径调节，可能成为未来研究的重点，旨在更好地理解哮喘与 PTSD 之间的关系，以及各个疾病的病理生理学。
