Disruption of brain white matter microstructure in women with anorexia nervosa

Disruption of brain white matter microstructure in women with anorexia nervosa

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J Psychiatry Neurosci 2014;39(6):367-75

Esther Via, MD; Andrew Zalesky, PhD; Isabel Sánchez, PhD; Laura Forcano, PhD; Ben J. Harrison, PhD; Jesús Pujol, MD; Fernando Fernández-Aranda, PhD, FAED; José Manuel Menchón, MD, PhD; Carles Soriano-Mas, PhD; Narcís Cardoner, MD, PhD; Alex Fornito, PhD

Via, Sánchez, Forcano, Fernández-Aranda, Menchón, Soriano-Mas, Cardoner — Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; Via, Fernández-Aranda, Menchón, Cardoner — Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain; Zalesky, Harrison — Melbourne Neuropsychiatry Centre, The University of Melbourne, Melbourne, Australia; Pujol — MRI Research Unit, CRC Mar, Hospital de Mar, Barcelona, Spain; Menchón, Soriano-Mas, Cardoner — CIBER Salud Mental (CIBERSAM), Instituto Carlos III, Barcelona, Spain; Forcano, Fernández-Aranda — CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Carlos III, Barcelona, Spain; Fornito — Monash Clinical and Imaging Neuroscience, School of Psychology and Psychiatry & Monash Biomedical Imaging, Monash University, Clayton, Australia


Background: The etiology of anorexia nervosa is still unknown. Multiple and distributed brain regions have been implicated in its pathophysiology, implying a dysfunction of connected neural circuits. Despite these findings, the role of white matter in anorexia nervosa has been rarely assessed. In this study, we used diffusion tensor imaging (DTI) to characterize alterations of white matter microstructure in a clinically homogeneous sample of patients with anorexia nervosa.

Methods: Women with anorexia nervosa (restricting subtype) and healthy controls underwent brain DTI. We used tract-based spatial statistics to compare fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups. Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from regions showing group differences in either FA or MD.

Results: We enrolled 19 women with anorexia nervosa and 19 healthy controls in our study. Patients with anorexia nervosa showed significant FA decreases in the parietal part of the left superior longitudinal fasciculus (SLF; pFWE < 0.05), with increased MD and RD but no differences in AD. Patients with anorexia nervosa also showed significantly increased MD in the fornix (pFWE < 0.05), accompanied by decreased FA and increased RD and AD. Limitations: Limitations include our modest sample size and cross-sectional design.

Conclusion: Our findings support the presence of white matter pathology in patients with anorexia nervosa. Alterations in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such as body image distortion or impairments in body–energy–balance and reward processes. The differences found in both areas replicate those found in previous DTI studies and support a role for white matter pathology of specific neural circuits in individuals with anorexia nervosa.

Submitted July 2, 2013; Revised Oct. 28, 2013, Jan. 31, 2014; Accepted Feb. 4, 2014; Early-released June 10, 2014.

Acknowledgements: This study was supported in part by the Carlos III Health Institute (PI081549, PI 11210). A. Zalesky is supported by a National Health and Medical Research Council of Australia (NHMRC) Biomedical Career Development Award (I.D. 1047648). B. Harrison is supported by a National Health and Medical Research Council of Australia (NHMRC) Clinical Career Development Award (I.D. 628509). C. Soriano-Mas is funded by a Miguel Servet contract from the Carlos III Health Institute (CP10/00604). A. Fornito is supported by a CR Roper Fellowship (University of Melbourne). CIBERSAM and CIBEROBN are both initiatives of ISCIII. The authors thank all of the study subjects as well as the staff from the Department of Psychiatry of Hospital Universitari de Bellvitge. We also thank E. Martínez-Heras, MSc (IDIBAPS, Barcelona) for his contribution in earlier phases of this study.

Competing interests: J.M. Menchón declares personal fees from Eli Lilly, Janssen, Lundbeck, Medtronic, Otsuka, Rovi and Servier. N. Cardoner declares personal fees from AstraZeneca, Eli Lilly, Esteve, Ferrer, Pfizer and Janssen. No other competing interests declared.

Contributors: E. Via, A. Zalesky, B.J. Harrison, J. Pujol, F. Fernández- Aranda, J.M. Menchón, C. Soriano-Mas, N. Cardoner and A. Fornito designed the study. E. Via, I. Sánchez, L. Forcano, J. Pujol, F. Fernández- Aranda, C. Soriano-Mas and N. Cardoner acquired the data, which E. Via, A. Zalesky, B.J. Harrison, J.M. Menchón, C. Soriano- Mas, N. Cardoner and A. Fornito analyzed. E. Via, A. Zalesky and A. Fornito wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130135

Correspondence to: N. Cardoner, Psychiatry Department, Bellvitge University Hospital, Feixa Llarga s/n, 08907, L’Hospitalet de Llobregat, Barcelona, Spain; ncardoner@bellvitgehospital.cat