Resilience, mental health, sleep, and smoking mediate pathways between lifetime stressors and Multiple Sclerosis severity.

Intro:Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to Multiple Sclerosis (MS) features; yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim:To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods:Adults with MS (N=924) participated in an online survey through the National MS Society listserv. Structural Equation Modeling was used to examine the direct and indirect effect of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity and interference), via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results:The final analytic model had excellent fit (GFI=0.998). Lifetime stressors had a direct relationship with MS severity (β=0.27, p<.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of mediation was significant (β=0.45). Conclusions:This work provides foundational evidence to inform conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve disease course.