BACKGROUND: Anorexia nervosa (AN) is a severe eating disorder associated with drastic reductions in gray and white matter (WM) volume and structural connectivity alterations. However, the hypotheses regarding underlying mechanisms are inconclusive. The current study investigated the relationships of WM volume as well as WM network architecture with neurofilament light (NF-L), a marker of axonal damage.

METHODS: Blood samples and magnetic resonance imaging scans from 77 predominantly adolescent female participants with acute AN were used. Associations of WM volume with NF-L were tested using linear models. The relationship between NF-L and alterations in brain networks was evaluated using network-based statistic (NBS) models, which predicted connectivity associated with NF-L levels. Additionally, associations with clinical variables and leptin were tested. To test the specificity of the results, control analyses were conducted on 77 female healthy participants (HC).

RESULTS: We found negative associations between NF-L concentrations and WM volume. NBS analyses identified seven components, where fractional anisotropy was positively associated with NF-L. In some components, mean connectivity was negatively associated with leptin concentrations. Mediation analyses suggested that the negative correlation of leptin and NF-L might be partially mediated by changes in WM microstructure. These effects were not observed in HC.

CONCLUSIONS: The results suggest that WM volume reductions in acute AN might be related to axonal damage. The NBS results indicate, that the elevated fractional anisotropy previously found in AN might be related to damage processes leading to axonal swelling. All in all, the present study supports NF-L as a global blood marker for brain damage processes in acute AN.