White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study
- 30 Downloads
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.
KeywordsAnorexia 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.
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.
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 was obtained from all individual participants included in the study.
- American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders: DSM-5™ (5th ed.). Arlington, VA, US: American Psychiatric Publishing, IncGoogle Scholar
- Darmanis, S., Sloan, S. A., Zhang, Y., Enge, M., Caneda, C., Shuer, L. M., Hayden Gephart, M. G., Barres, B. A., & Quake, S. R. (2015). A survey of human brain transcriptome diversity at the single cell level. Proceedings of the National Academy of Sciences, 112(23), 7285–7290.CrossRefGoogle Scholar
- Fairburn, C. G. & Beglin, S. J. (2008). Eating disorder examination questionnaire (EDE-Q 6.0). In Cognitive behavior therapy and eating disorders (pp. 309–313).Google Scholar
- Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., ... & Montillo, A. (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355Google Scholar
- Fischl, B., Van Der Kouwe, A., Destrieux, C., Halgren, E., Ségonne, F., Salat, D. H., ... & Caviness, V. (2004). Automatically parcellating the human cerebral cortex. Cerebral cortex, 14(1), 11–22Google Scholar
- Kochunov, P., Jahanshad, N., Marcus, D., Winkler, A., Sprooten, E., Nichols, T. E., … Van Essen, D. C. (2015). Heritability of fractional anisotropy in human white matter: A comparison of human connectome project and ENIGMA-DTI data. NeuroImage, 111, 300–301.PubMedPubMedCentralCrossRefGoogle Scholar
- Mancarci, B. O., Toker, L., Tripathy, S. J., Li, B., Rocco, B., Sibille, E. & Pavlidis, P. (2017). Cross-laboratory analysis of brain cell type transcriptomes with applications to interpretation of bulk tissue data. Eneuro, 4(6), ENEURO.0212-17.2017.Google Scholar
- Miles, A. E., Voineskos, A. N., French, L., & Kaplan, A. S. (2018). Subcortical volume and cortical surface architecture in women with acute and remitted anorexia nervosa: An exploratory neuroimaging study. Journal of psychiatric research, 102, 179–185Google Scholar
- Mori, S., Oishi, K., Jiang, H., Jiang, L., Li, X., Akhter, K., Hua, K., Faria, A. V., Mahmood, A., Woods, R., Toga, A. W., Pike, G. B., Neto, P. R., Evans, A., Zhang, J., Huang, H., Miller, M. I., van Zijl, P., & Mazziotta, J. (2008). Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. NeuroImage, 40(2), 570–582.PubMedPubMedCentralCrossRefGoogle Scholar
- Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., Bannister, P. R., de Luca, M., Drobnjak, I., Flitney, D. E., Niazy, R. K., Saunders, J., Vickers, J., Zhang, Y., de Stefano, N., Brady, J. M., & Matthews, P. M. (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage, 23(SUPPL. 1), S208–S219.PubMedCrossRefGoogle Scholar
- Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., Watkins, K. E., Ciccarelli, O., Cader, M. Z., Matthews, P. M., & Behrens, T. E. J. (2006). Tract based spatial statistics: Voxelwise analysis of multi-subjects diffusion data. NeuroImage, 31(4), 1487–1505.PubMedCrossRefGoogle Scholar