Supplementary Material for: Association Between Psychiatric Disorders and Amyotrophic Lateral Sclerosis: A Prospective Cohort Study from the UK

Introduction: Psychiatric disorders have been reported to be associated with amyotrophic lateral sclerosis (ALS). However, evidence for the association remains inconsistent, and it is unclear whether specific categories of psychiatric disorders constitute risk factors for ALS. The study aimed to investigate the association between different categories of psychiatric disorders and the risk of ALS.
Methods: We utilized data from the UK Biobank to conduct a population-based prospective cohort study. Cox proportional hazards models were employed to evaluate the association between a history of various psychiatric disorders including schizophrenia, bipolar disorder, depression, anxiety, stress-related disorders and the risk of ALS. Analyses were adjusted for covariates including sociodemographic factors, lifestyle factors and medical history.
Results: Among the 484,065 participants initially included, 558 participants were diagnosed with ALS during a median follow-up of 13.63 years. With complete adjustment, previous schizophrenia (hazard ratio [HR] 6.32; 95% confidence interval [CI] 2.60-15.36; p<0.001) and depression (HR 1.37; 95% CI 1.03-1.81; p=0.03) were found to be significantly associated with ALS.
Conclusion: This large prospective cohort study indicated the association between schizophrenia, depression and a higher risk of subsequent ALS. These findings suggest potential implications for early process of global neurodegeneration in ALS, underlining the need for further research to explore the underlying mechanisms.

引言：有研究表明精神障碍与肌萎缩侧索硬化症（amyotrophic lateral sclerosis, ALS）存在关联，但目前二者间的关联证据仍不统一，且尚不明确特定类别的精神障碍是否为ALS的危险因素。本研究旨在探讨不同类别精神障碍与ALS发病风险之间的关联。
方法：本研究依托英国生物样本库（UK Biobank）数据，开展一项基于人群的前瞻性队列研究。采用Cox比例风险模型（Cox proportional hazards models）评估各类精神障碍（包括精神分裂症、双相障碍、抑郁障碍、焦虑障碍、应激相关障碍）病史与ALS发病风险之间的关联。分析过程针对社会人口学因素、生活方式因素及既往病史等混杂因素进行了校正。
结果：初始纳入的484065名研究对象中，经中位随访13.63年，共有558人被确诊为ALS。经完全校正后，既往罹患精神分裂症（风险比[HR] 6.32；95%置信区间[CI] 2.60~15.36；p<0.001）与抑郁障碍（HR 1.37；95%CI 1.03~1.81；p=0.03）均与ALS发病风险显著相关。
结论：这项大型前瞻性队列研究证实，精神分裂症、抑郁障碍与后续ALS的更高发病风险存在关联。本研究结果提示其对ALS的全域神经退行性病变早期进程可能具有潜在意义，同时凸显了开展进一步研究以探索其潜在机制的必要性。