Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

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J Psychiatry Neurosci 2016;41(1):6-15

Daniel Geisler, MSc*; Viola Borchardt, MSc*; Anton R. Lord, PhD; Ilka Boehm, MSc; Franziska Ritschel, MSc; Johannes Zwipp, MSc; Sabine Clas; Joseph A. King, PhD; Silvia Wolff-Stephan, PhD; Veit Roessner, MD; Martin Walter, MD; Stefan Ehrlich, MD

Abstract

Background: Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact.

Methods: To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities.

Results: Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus.

Limitations: The present results may be limited to the methods applied during preprocessing and network construction.

Conclusion: We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger.


*These authors contributed equally to this work.

Submitted Oct. 20, 2014; Revised Mar. 6, 2015; Accepted Mar. 20, 2015; Early-released Aug. 11, 2015

Affiliations: From the Department of Child and Adolescent Psychiatry, Eating Disorder Services and Research Center, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Germany (Geisler, Boehm, Ritschel, Zwipp, Clas, King, Roessner, Ehrlich); the Leibniz Institute for Neurobiology, Magdeburg, Germany (Borchardt, Lord, Walter); the Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany (Borchardt, Lord, Walter); the Department of Psychosomatic Medicine and Psychotherapy, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Germany (Wolff-Stephan); the Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany (Walter); the Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany (Walter); the MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Mass. ( Ehrlich); and the Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Boston, Mass. (Ehrlich).

Acknowledgments: This work was supported by the Deutsche Forschungsgemeinschaft (EH 367/5-1, SFB 940 & SFB 779), the Swiss Anorexia Nervosa Foundation, the Center for Behavioral Brain Sciences (CBBS) and by a EU-Marie Curie grant (MC-ITN-R’Birth). The authors thank the medical students, research assistants and clinicians who assisted with participant recruitment and data collection and thank all participants for their time and cooperation. The authors also thank the Center for Information Services and High Performance Computing (ZIH) at TU Dresden for generous allocations of computer time.

Competing interests: V. Roessner has received payment for consulting and writing activities from Lilly, Novartis, and Shire Pharmaceuticals, lecture honoraria from Lilly, Novartis, Shire Pharmaceuticals, and Medice Pharma, and support for research from Shire and Novartis. He has carried out (and is currently carrying out) clinical trials in cooperation with the Novartis, Shire, and Otsuka companies. M. Walter has received travel support and research awards or research support from AstraZeneca, Hexal, GlaxoSmithKline, and Janssen Research. No other competing interests declared.

Contributors: D. Geisler, V. Roessner and S. Ehrlich designed the study. D. Geisler, I. Böhm, F. Ritschel, Y. Zwipp, S. Clas, J.A. King, S. Wolff-Stephan and S. Ehrlich acquired the data, which D. Geisler, V. Borchardt, A. Lord, J.A. King, M. Walter and S. Ehrlich analyzed. D. Geisler, V. Borchardt, A. Lord, J.A. King and S. Ehrlich wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140310

Correspondence to: S. Ehrlich, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Fetscherstraße 74, 01307 Dresden, Germany; transden.lab@uniklinikum-dresden.de