Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

Esther Walton, Fabio Bernardoni, Victoria Luise Batury, Klaas Bahnsen, Sara Larivière, Giovanni Abbate-Daga, Susana Andres-Perpiña, Lasse Bang, Amanda Bischoff-Grethe, Samantha J. Brooks, Iain C. Campbell, Giammarco Cascino, Josefina Castro-Fornieles, Enrico Collantoni, Federico D'Agata, Brigitte Dahmen, Unna N. Danner, Angela Favaro, Jamie D. Feusner, Guido K.W. FrankHans Christoph Friederich, John L. Graner, Beate Herpertz-Dahlmann, Andreas Hess, Stefanie Horndasch, Allan S. Kaplan, Lisa Katrin Kaufmann, Walter H. Kaye, Sahib S. Khalsa, Kevin S. LaBar, Luca Lavagnino, Luisa Lazaro, Renzo Manara, Amy E. Miles, Gabriella F. Milos, Alessio Maria Monteleone, Palmiero Monteleone, Benson Mwangi, Owen O'Daly, Jose Pariente, Julie Roesch, Ulrike H. Schmidt, Jochen Seitz, Megan E. Shott, Joe J. Simon, Paul A.M. Smeets, Christian K. Tamnes, Elena Tenconi, Sophia I. Thomopoulos, Annemarie A. van Elburg, Aristotle N. Voineskos, Georg G. von Polier, Christina E. Wierenga, Nancy L. Zucker, Neda Jahanshad, Joseph A. King, Paul M. Thompson, Laura A. Berner, Stefan Ehrlich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Original languageEnglish
Pages (from-to)730-738
Number of pages9
JournalBiological psychiatry
Issue number9
Publication statusPublished - 1 Nov 2022


  • BMI
  • Cortical thickness
  • MRI
  • Subcortical volume
  • Surface area


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