White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study

Abstract

Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight restoration. In this exploratory neuroimaging study, we sought to characterize changes in white matter microstructure in women with acute and remitted AN. Diffusion-weighted MRI data was collected from underweight women with a current diagnosis of AN (acAN: n=23), weight-recovered women with a past diagnosis of AN (recAN: n=23), and age-matched healthy control women (HC: n=24). Image processing and analysis were performed with Tract-Based Spatial Statistics, part of FSL, and group differences in voxel-wise, brain-wide fractional anisotropy (FA) and mean diffusivity (MD), indices of white matter microstructure, were tested with nonparametric permutation and threshold free cluster enhancement. No significant main effect of group on FA was identified. A significant main effect of group on MD was observed in a large cluster covering 9.2% of white matter and including substantial portions of the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus, and post hoc analyses revealed similar effects of group on axial diffusivity (AD) and radial diffusivity (RD). Cluster-wise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for cluster-wise AD and RD. Trait-based increases in diffusivity, consistent with atypical myelination and impaired axon integrity, suggest a link between altered white matter microstructure and vulnerability to AN, and evidence of reduced oligodendrocyte density in AN provides further support for this hypothesis. Potential mechanisms of action include atypical neurodevelopment and systemic inflammation.