The Impact of Child and Adult Stressors on Multiple Sclerosis Biopsychosocial Disease Features

Abstract

Background: Multiple Sclerosis (MS) is a neuroinflammatory demyelinating autoimmune disease of the central nervous system that disproportionately affects people in North America. Although the etiology and cure remain unknown, interactions among genetic, environmental (e.g., latitude), and behavioral (e.g., smoking) influences are considered contributing factors. The Social Safety Theory offers a pathway from stress to disease through the physiological responses of the inflammation cascade. Through this cascade, childhood stressors have been implicated in the development of many physical health conditions including heart disease, stroke, Alzheimer’s disease, obesity, diabetes, and numerous autoimmune diseases. Childhood stressors are also linked with behavioral and mental health outcomes including perceived stress in adulthood and substance use. Adult stress has been associated with MS onset and relapses. Although traumatic stressors have been associated with the development of autoimmune diseases, remarkably few studies (n=5) have investigated the relationship between childhood stressors and MS disease features. Of these studies, none accounted for adult stressors, and few accounted for MS specific covariates.

Purpose: The purpose of this cross-sectional study was to evaluate relationships among childhood adversity, adult stressors, and features of MS while accounting for MS specific confounders. Guided by the Social Safety Theory, this work posits that child and adult stressors are social threats which elicit neuroinflammatory responses contributing to MS symptoms.

Methods: An electronic invitation was sent to the National MS Society listserv of 80,000 people with MS, and 924 participants successfully completed the survey. The aims of this dissertation include to examine the associations between: 1) cumulative child stressor characteristics (e.g., severity, duration), and cumulative adult stressor characteristics with individual MS disease outcome features; 2) child stressor types, grouped by emotional, physical, and environmental, and MS disease features; and 3) individual lifetime stressor type characteristics (e.g., physical danger severity) and MS disease features. Hierarchical block modeling was used for aims 1 and 2 to assess the shared contribution of similar stressors, while multiple regression was used for aim 3.

Results: For aim 1, hierarchical block modeling was used to sequentially assess childhood cumulative and adult cumulative stressors in relation to the six MS outcomes. Both child and adult stressors were associated with three outcomes, pain interference, disability, and mental health comorbidity. Only child stressors were associated with fatigue, while only adult stressors were associated with relapse burden changes since Covid-19. The age at symptom onset was not significantly associated with any stressors. For aim 2, hierarchical block modeling was used to sequentially assess childhood stressors, grouped by emotional, physical, and environmental stressors. At least two types of childhood stressors were significantly associated with all MS feature outcomes, except the relapse burden change since Covid-19 which was unaffected by stressors. For aim 3, multiple regression was used to assess cumulative stressors across the lifespan, grouped into five core social-psychological types, and the same six MS features. Stressors were significantly associated with four features, fatigue, pain interference, age at symptom onset, and mental health comorbidity. Stressors did not impact disability or relapse burden change.

Conclusions: Findings across all aims fill gaps and advance knowledge in this field. This dissertation supports relationships between stressors experienced across the lifespan and common clinical features of MS.