Abstract
BACKGROUND AND PURPOSE: Unexpected stressful life events may alter immune function and affect susceptibility to autoimmune diseases including multiple sclerosis (MS). Current results from epidemiological investigations examining the role of stress in MS remain inconsistent. The aim was to conduct the hitherto largest population-based case-control study on this topic. METHODS: Extensive questionnaire information collected on lifestyle environmental factors available for 2930 incident MS cases and 6170 controls were used to assess the association of 10 major life events that had occurred before disease onset with the risk of MS by unconditional logistic regressions, adjusting for potential confounders. Stratified analyses were also performed by sex and time. RESULTS: Compelling evidence was found for a link between major life events and risk of MS - most events significantly increased disease risk by 17%-30%. It was further observed that women were affected to a greater extent than men under certain stressful scenarios, and that most events that happened recently (≤5 years prior to MS onset) had significant effects on MS, indicating a critical window in disease development. CONCLUSION: Stressful life events may have an adverse effect on the risk of MS. Research into the mechanisms of this observation may give important clues to triggering pathogenetic events in MS.