Increased Prevalence of an Oxytocin Receptor Gene Variant in Functional Neurological Disorder: A Case-Control Study

Eighty-five patients with mixed FND symptoms and 76 healthy control (HC) individuals were genotyped for 10 single-nucleotide polymorphisms (SNPs) in seven genes associated with the brain's stress response system. For genetic variants that were found to be linked to FND, associations with structural brain alterations were investigated by using a region-of-interest approach in a subset of FND patients with complete genotyping and neuroimaging data (N=82). Regions had been previously selected on the basis of their biological involvement and being a factor in vulnerability to FND.

A significant association between FND and a SNP, rs53576, in the oxytocin receptor (OXTR) gene was observed, and a significant association between decreased right insular volumes and rs53576 was also identified. Among female FND patients (N=60), the rs53576 SNP in OXTR was associated with significantly reduced bilateral amygdalar volume.

These preliminary results suggest that genetic factors in the oxytocinergic system and sex-specific structural changes in the insula and amygdala contribute to vulnerability to FND. Because oxytocin is a regulatory factor in stress responses, decreased activity of some FND-associated OXTR gene variants might affect stress responses and regulation in FND in a sex-dependent manner.