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

  • Amy E. MilesEmail author
  • Allan S. Kaplan
  • Leon French
  • Aristotle N. Voineskos
Original Research


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 voxelwise, 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). Clusterwise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for clusterwise AD and RD. Trait-based increases in diffusivity, changes in which have been associated 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.


Anorexia nervosa Diffusion tensor imaging White matter microstructure 



We thank Andrew Jaffe and Joel E. Kleinman for providing eating disorder subtype information for the GSE60190 expression dataset.

We also thank staff at the CAMH Research Imaging Centre and members of the Kimel Family Translational Imaging-Genetics Laboratory, particularly Dr. Erin Dickie, for their assistance with MRI acquisition and processing.

Funding information

This study was funded by the AFP Innovation Fund (CAM-114-001, CAM-116-003).

Compliance with ethical standards

Conflict of interest

Amy Miles declares that she has no conflict of interest. Leon French declares that he has no conflict of interest. Aristotle Voineskos declares that he has no conflict of interest. Allan Kaplan has received speaker honoraria and lecture fees from Shire Pharmaceuticals.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Centre for Addiction and Mental HealthTorontoCanada
  2. 2.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  3. 3.Department of PsychiatryUniversity of TorontoTorontoCanada
  4. 4.Computational Neurobiology Lab, Centre for Addiction and Mental HealthCampbell Family Mental Health Research InstituteTorontoCanada
  5. 5.Krembil Centre for Neuroinformatics, Centre for Addiction and Mental HealthTorontoCanada
  6. 6.Centre for Addiction and Mental HealthCampbell Family Mental Health Research InstituteTorontoCanada

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