Longitudinal white matter changes in anorexia nervosa: an exploratory fixel-based study

Abstract

Abstract Background This longitudinal study examined fiber-specific white matter (WM) changes in young women with restrictive-type anorexia nervosa (AN) during hospitalization and six months after discharge. Using advanced diffusion MRI methods, we aimed to characterize longitudinal WM changes during this interval. Methods Seventeen women with AN underwent MRI scanning and assessments of eating disorder symptoms and cognitive flexibility at two time points: after hospital admission (baseline) and six months after discharge (follow-up). Diffusion-weighted data were analyzed using fixel-based analysis to assess fiber density (FD), fiber-bundle cross-section (FC), and their combined metric (FDC) in tracts implicated in AN. Linear mixed-effects models examined the effects of time, age, body mass index (BMI), and their interactions. Results Longitudinal analyses showed a significant increase in FDC in the right cingulum in the follow-up period (q = 0.017, β = 0.367). Significant time × age interactions were observed in the posterior midbody of the corpus callosum (q = 0.008, β = 0.118) and left uncinate fasciculus (q = 0.008, β = 0.195), with older participants showing greater increases in FC over time. Participants also demonstrated significant BMI increases and improved cognitive flexibility, whereas eating disorder symptom measures did not significantly change. Conclusions These findings provide evidence of fiber-specific longitudinal WM changes in young women with AN during six-month follow-up after hospitalization. Age-related differences in FC changes were also observed. However, without longitudinal healthy controls, these changes cannot be attributed specifically to AN recovery, nutritional restoration, treatment, or normal development. Future studies with healthy controls are needed to disentangle these effects.