Association of lifestyle, psychological, and biological risk factors with multiple sclerosis: A case-control study

Abstract

Objectives: This study aimed to assess the prevalence and associations between lifestyle, psychological, and biological risk factors and the presence of multiple sclerosis (MS).

Patients and methods: A cross-sectional, observational, case-control study was conducted including 278 patients (105 males, 173 females; median age: 33 years; range, 16 to 61 years) with MS and 291 age-, sex-, and region-matched healthy controls (100 males, 191 females; median age: 33 years; range, 19 to 63 years) between January 1, 2013, and December 31, 2022. Multiple sclerosis diagnoses were based on national clinical guidelines. Risk factors assessed included smoking (active and passive), alcohol use (Alcohol Use Disorders Identification Test), physical activity (International Physical Activity Questionnaire-Short Form), vitamin D levels, Epstein-Barr virus (EBV) serostatus, body mass index, perceived stress (Perceived Stress Scale-10), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9). Data were collected using structured interviews and validated scales. Logistic regression (univariate and multivariate) was performed to estimate adjusted odds ratios (ORs) for MS risk, with additional interaction and sex-stratified analyses.

Results: Patients with MS had significantly higher rates of vitamin D deficiency (59.7% vs. 43.0%), EBV seropositivity (93.5% vs. 82.8%), physical inactivity (69.4% vs. 32.3%), high stress (41.4% vs. 29.2%), severe anxiety (27.0% vs. 14.8%), and severe depression (9.7% vs. 2.7%) compared to controls (p<0.001 for all). Multivariate regression identified the following independent protective factors: ≤9.9 pack-years of smoking (OR=0.30), no passive smoking before age 17 (OR=0.41), alcohol abstinence (OR=0.49), health-enhancing physical activity (OR=0.18) and minimal physical activity (OR=0.36), sufficient (OR=0.47) and insufficient (OR=0.51) vitamin D, EBV seronegativity (OR=0.35), moderate anxiety (OR=0.37), and mild depression (OR=0.25). A significant interaction between moderate stress and insufficient vitamin D levels was observed in females, with MS odds approximately 4.3 times higher in those exposed to both factors. Sex-stratified models indicated stronger associations with lifestyle factors in males and a greater contribution of psychological variables among females.

Conclusion: Multiple sclerosis susceptibility appears to be associated with multiple modifiable factors. Physical activity, vitamin D sufficiency, and EBV seronegativity showed strong negative associations with MS. Lifestyle-related exposures, such as alcohol use and smoking, were more strongly associated with MS in males, while psychological factors (stress, anxiety, and depression) demonstrated stronger associations in females. The observed interaction between moderate stress and insufficient vitamin D levels suggests a potential synergistic pattern that may warrant further investigation. These findings support the importance of a multifactorial perspective in MS research, emphasizing the need for sex-specific risk profiling. Longitudinal and mechanistic studies are needed to validate these associations and clarify potential causal pathways.

Cite this article as: Aliyev R, Mammadbayli A, Shiraliyeva R. Association of lifestyle, psychological, and biological risk factors with multiple sclerosis: A case-control study. Turk J Neurol 2025;31(3):278-293. doi: 10.55697/tnd.2025.494.