Methylome changes associated with functional movement/conversion disorder: Influence of biological sex and childhood...

Epigenetic changes, such as DNA methylation (DNAm), may represent an important mechanism implicated in the etiopathogenesis of functional movement/conversion disorder (FMD). Here, we aimed to identify methylomic variations in a case-control cohort of FMD and to uncover specific epigenetic signatures associated with female sex and childhood abuse, two key risk factors for FMD and other functional neurological disorders. Genome-wide DNAm analysis was performed from peripheral blood in 57 patients with FMD and 47 healthy controls with and without childhood abuse. Using principal component analysis, we examined the association of principal components with FMD status in abused and non-abused individuals, in the entire study sample and in female subjects only. Next, we used enrichment pathway analysis to investigate the biological significance of DNAm changes and explored differences in methylation levels of genes annotated to the top enriched biological pathways shared across comparisons. We found that FMD was associated with DNAm variation across the genome and identified a common epigenetic 'signature' enriched for biological pathways implicated in chronic stress and chronic pain. However, methylation levels of genes included in the top two shared pathways hardly overlapped, suggesting that transcriptional profiles may differ as a function of childhood abuse exposure and sex among subjects with FMD. This study is unique in providing genome-wide evidence of DNAm changes in FMD and in indicating a potential mechanism linking childhood abuse exposure and female sex to differences in FMD pathophysiology. Future studies are needed to replicate our findings in independent cohorts.