Brain morphology in Anorexia Nervosa and its subtypes: A multi-cohort study of individual participant data

Fabio Bernardoni, Dominic Arold, Luis Schoppik, Klaas Bahnsen, Ruiyang Ge, Clara Moreau, Lasse Bang, Federico D’Agata, Giovanni Abbate-Daga, Christian K Tamnes, Iain Campbell, Owen O’Daly, Ulrike Schmidt, Guido Frank, Stefanie Horndasch, Andreas Hess, Arnd Dörfler, Hans-Christoph Friederich, Joe Simon, Angela Favaro, Luca Lavagnino, Christina E Wierenga, Amanda Bischoff-Grethe, Amy E Miles, Allan Kaplan, Aristotle Voineskos, Paul A M Smeets, Annemarie A van Elburg, Unna Danner, Sophia I Thomopoulos, Laura Berner, Neda Jahanshad, Sophia Frangou, Joseph A King, Paul Thompson and Stefan Ehrlich

PLOS Medicine, 2026, vol. 23, issue 5, 1-20

Abstract: Background: In a recent coordinated meta-analysis of neuroimaging data, we reported gray matter (GM) alterations in acutely underweight patients with anorexia nervosa (AN). Here, we extend these findings by examining individual variation in brain structure within AN, individual-level differentiation between AN and healthy controls (HC), and differences between AN subtypes, with potential relevance for understanding clinical heterogeneity. Methods and findings: We analyzed individual-level data from 11 international sites in the ENIGMA Eating Disorders Working Group, including 570 female participants with AN and 739 HC. We examined cortical thickness, cortical surface area and subcortical volumes in AN versus HC using three complementary approaches: (i) group-level differences in a mega-analysis correcting for age effects, (ii) frequencies of extreme deviations (infra-/supranormal; z 1.96) based on normative reference models by the CentileBrain Initiative, and (iii) individual-level classification performance using machine learning. The same analytic framework was applied to compare AN restricting versus binge-eating/purging subtype, additionally correcting for BMI effects. Conclusion: Using a mega-analytic approach, we confirm widespread GM deficits in AN, show that these alterations are (in some patients) extreme, and demonstrate that they enable robust classification with superior performance compared to most MRI-based psychiatric classification studies. The absence of differences between AN subtypes may reflect shared neurobiology, though other imaging modalities may reveal distinctions beyond brain structure. Why was this study done?: What did the researchers do and find?: What do these findings mean?: In a multi-cohort study, Bernardoni and colleagues investigate potential brain structure differences between patients with Anorexia Nervosa (AN), and AN patients versus healthy controls, using individual participant data.

Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pmed00:1004809

DOI: 10.1371/journal.pmed.1004809

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