High odds of multiple sclerosis following major life stressors: Evidence from a population-based case-control study in Northern Iran.

Abstract

Background: Psychological stress has been proposed as a trigger of multiple sclerosis (MS) onset, yet population-based evidence remains inconsistent across cultures. This study examined the association between major stressful life events and MS susceptibility in Northern Iran. Methods: In a case-control study conducted between 2023 and 2025 in Mazandaran Province, Iran, 300 patients with definite MS and 300 age- and sex-matched healthy controls were enrolled. Exposure to major stressful life events during the five years preceding disease onset (for cases) or interview (for controls) was assessed using the validated Persian version of the Environmental Risk Factor Questionnaire (EnvIMS-Q). Logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: Exposure to at least one major stressful life event was reported by 92.7% of MS cases and 62.7% of controls (P < 0.001). After adjustment for demographic variables, six independent stressors were significantly associated with MS: marital separation (OR = 8.95, 95% CI: 1.92-41.6), financial debt (OR = 4.72, 95% CI: 2.73-8.16), death of a close relative (OR = 3.57, 95% CI: 2.25-5.66), unemployment or financial dependency (OR = 4.19, 95% CI: 1.64-10.7), serious personal illness or injury (OR = 2.66, 95% CI: 1.64-4.32), and marriage (OR = 3.99, 95% CI: 2.15-7.40). The identification of marriage as a stressor is contextually novel and may reflect region-specific psychosocial pressures. Conclusion: Major life stressors appear to contribute to MS susceptibility, with certain stressors such as marriage showing culture-dependent associations. These findings provide new insight into sociocultural factors influencing MS risk in Iranian populations. These findings should be interpreted with caution and confirmed in longitudinal studies.