Association between Psychiatric Disorders and Amyotrophic Lateral Sclerosis: A Prospective Cohort Study from the UK Biobank

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. (c) 2025 S. Karger AG, Basel