White matter microstructural differences in underweight adolescents with anorexia nervosa and a preliminary longitudinal investigation of change following short-term weight restoration

Purpose: Anorexia nervosa (AN) affects approximately 2.9% of females and has the highest mortality rate among all psychiatric disorders. Despite several advances, the neurobiology of this disorder is still not well understood. Several studies have reported abnormalities in the white matter, but it is not know if these are disease-related or secondary to undernutrition. This study aimed to further our understanding of white matter pathology using diffusion-weighted imaging in underweight adolescents with AN, and to examine changes occurring after short-term weight restoration. Methods: Analyses were conducted on diffusion-weighted imaging from 24 female adolescents with AN and 17 age- and gender-matched healthy controls (HC), aged 14–19 years. Groups were compared on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) using tract-based spatial statistics analysis and DTI measures were correlated with eating disorder examination questionnaire (EDE-Q) subscales and body mass index (BMI). Preliminary repeated-measure analyses were also conducted on eight participants after short-term weight restoration (median 41 days). Results: Widespread increases in MD of up to 9% were found in underweight AN relative to HC, particularly in the corpus callosum. This was associated with both increased AD and RD, suggestive of dys- or de-myelination. There were no significant group differences in FA, and no significant correlations between DTI measures, BMI or EDE-Q subscale score. Weight restoration therapy significantly reduced MD, to levels significantly lower than HC, but did not consistently alter FA across individuals. Conclusions: White matter microstructure is significantly altered in female adolescents with AN, with preliminary longitudinal data suggesting that it may be reversible with short-term weight restoration. Level of evidence Level III: evidence obtained from well-designed cohort or case–control analytic studies.