Adverse Childhood Experiences and the Risk of Multiple Sclerosis Development: A Review of Potential Mechanisms

Abstract

Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, contribute to long-term systemic toxic stress and inflammation that may last well into adulthood. Such early-life stressors have been associated with increased susceptibility to multiple sclerosis (MS) in observational studies and with the development of experimental autoimmune encephalomyelitis in animal models. In this review, we summarize the evidence for an ACE-mediated increase in MS risk, as well as the potential mechanisms for this association. ACEs dysregulate neurodevelopment, stress responses, and immune reactivity; they also alter the interplay between the immune system and neural networks. All of this may be relevant for MS risk. We further discuss how ACEs induce epigenetic changes and how the toxic stress caused by ACEs may reactivate the Epstein-Barr Virus (EBV), a key risk factor for MS. We conclude by suggesting new initiatives to obtain further insights into this topic.

Keywords: MS; abuse; childhood; early; stress; trauma; violence.

Figure 1

An illustration of potential pathways through which adverse childhood experiences (ACEs) can interact with genetic susceptibility and behavioral trajectories. ACEs induce toxic stress responses, which cause disruptions in neurological, endocrine, immune, and metabolic pathways and alter genetic function and expression. These changes increase the risk of adverse health and disease throughout the lifespan. The same pathways increase MS susceptibility. Reproduced in line with Creative Commons CC-BY-NC 4.0 license. ©2020 by British Medical Journal Publishing Group [27].