Lin Anqi, Mai Yiyin, Lai Guichuan, Li Zhengrui, Shen Junyi, Wong Hank Z H, Zhang Nan, Zhang Jian, Li Kailai, Cheng Quan, Ye Bicheng, Jiang Aimin, Luo Peng, Jia Guiqing, Chen Qunqing
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical University), Lianyungang, 222000, China.
Mol Psychiatry. 2025 Sep 16. doi: 10.1038/s41380-025-03252-1.
Taxane drugs are essential chemotherapeutic agents in the clinical management of various solid tumors; however, their associated psychiatric adverse effects and underlying mechanisms remain insufficiently explored. This study aims to assess the association between taxane drugs and psychiatric adverse events (pAEs) and to investigate their potential biological mechanisms. The association between taxane drugs and pAEs was analyzed using the reporting odds ratio (ROR) method based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) (2013-2023) and the World Health Organization's global pharmacovigilance database (Vigibase database). Tumor-bearing mouse models treated with taxane drugs were developed, and RNA sequencing was conducted to examine the underlying molecular mechanisms. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the activity of relevant pathways. A total of 10,132 cases and 10,525 cases of pAEs associated with taxane drugs were identified in the FAERS and Vigibase databases, respectively. Nine significant taxane-related psychiatric adverse events (TX-related pAEs) were identified, with emotional distress showing the strongest signal. Subgroup analysis indicated that women (ROR = 15.244), individuals younger than 45 years (ROR = 17.849), and breast cancer patients exhibited a higher risk. Mechanistic studies revealed four significantly associated signaling pathways: cobalamin metabolic process, regulation of response to oxidative stress, G protein-coupled receptor signaling, and nitric oxide-mediated signal transduction. This study is the first to systematically assess taxane drug-associated pAEs, elucidating the characteristics of high-risk populations and underlying molecular mechanisms, thereby offering valuable insights for clinical drug safety and personalized treatment.
紫杉烷类药物是多种实体瘤临床治疗中的重要化疗药物；然而，其相关的精神科不良反应及其潜在机制仍未得到充分探索。本研究旨在评估紫杉烷类药物与精神科不良事件（pAEs）之间的关联，并探究其潜在的生物学机制。基于美国食品药品监督管理局不良事件报告系统（FAERS）（2013 - 2023年）和世界卫生组织全球药物警戒数据库（Vigibase数据库）的数据，采用报告比值比（ROR）方法分析紫杉烷类药物与pAEs之间的关联。构建了用紫杉烷类药物治疗的荷瘤小鼠模型，并进行RNA测序以研究潜在的分子机制。进行单样本基因集富集分析（ssGSEA）以评估相关通路的活性。在FAERS和Vigibase数据库中分别确定了10132例和10525例与紫杉烷类药物相关的pAEs。确定了9种与紫杉烷相关的显著精神科不良事件（TX相关pAEs），其中情绪困扰的信号最强。亚组分析表明，女性（ROR = 15.244）、45岁以下个体（ROR = 17.849）和乳腺癌患者的风险更高。机制研究揭示了四个显著相关的信号通路：钴胺素代谢过程、氧化应激反应调节、G蛋白偶联受体信号传导和一氧化氮介导的信号转导。本研究首次系统评估了紫杉烷类药物相关的pAEs，阐明了高危人群的特征和潜在分子机制，从而为临床药物安全性和个性化治疗提供了有价值的见解。
