Childhood Adversity is Associated With Greater MS Symptoms, Disability Scores, and Epigenetic Changes in Pediatric and Adult-onset Multiple Sclerosis
Kimberly O'Neill1, Bernard van der Veer2, Leigh Charvet1, Nadine Azmy1, Steven Friedman1, Jiyuan Hu1, Kevin Lei3, Robin Ortiz1, Shayna Pehel1, Yidan Shi1, Anna Sosa1, Kian Koh3, Mirjana Maletic-Savatic3, Lauren Krupp1
1NYU Grossman School of Medicine, 2KU Leuven, 3Baylor College of Medicine
Objective:
To describe associations between childhood adversity and multiple sclerosis (MS) symptoms and disability in early adulthood among pediatric-onset MS and adult-onset MS. Epigenetic changes are also assessed.
Background:
Childhood adversity is increasingly recognized as a critical modifier of neurologic disease, including in MS. While the underlying biological mechanisms remain poorly understood, epigenetic modifications may be a potential pathogenic mechanism.
Design/Methods:
We evaluated 60 consecutively enrolled young adults with MS; 30 with pediatric-onset MS (POMS) and 30 with adult-onset MS (AOMS). Childhood adversity was defined using a composite index of the Adverse Childhood Experiences (ACEs) questionnaire, parental education level, and estimated household income during childhood. Clinical outcomes included patient-reported SymptoMScreen questionnaire regarding MS symptom burden and MS neurologist-assessed disability using the Expanded Disability Status Scale (EDSS) of the participant’s neurologic exam at the time of enrollment. Genome-wide epigenetic profiles (DNA methylation via RRBS; reduced representation bisulfite sequencing) were also assessed.
Results:
At time of enrollment in this cross-sectional study, participants had MS disease duration of 6 years on average. POMS participants were mean 22.09 (2.66) years and AOMS participants were mean 32.41 (2.19) years old. 62% of participants were female. 26 participants met criteria for high childhood adversity and 34 participants did not. Individuals with high childhood adversity reported greater SymptoMScreen composite scores compared to individuals with low childhood adversity (15.12 vs 7.54, p=0.001). Among individuals with EDSS scores above 0, 6/24 (10%) had a history of low childhood adversity compared to 18/24 (30%) with a history of high childhood adversity, p=0.027. Furthermore, POMS participants with high childhood adversity had increased DNA methylation.
Conclusions:
Our findings suggest that childhood adversity is associated with increased MS symptom burden and neurologic disability in young adults with MS. Epigenetic changes associated with childhood adversity were especially notable among the POMS population.
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