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

Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung

Beitragende

  • Fabio Bernardoni - , Psychosoziale Medizin und Entwicklungsneurowissenschaften (Autor:in)
  • Dominic Arold - , Psychosoziale Medizin und Entwicklungsneurowissenschaften (Autor:in)
  • Luis Schoppik - , Psychosoziale Medizin und Entwicklungsneurowissenschaften (Autor:in)
  • Klaas Bahnsen - , Psychosoziale Medizin und Entwicklungsneurowissenschaften, King's College London (KCL) (Autor:in)
  • Ruiyang Ge - , University of British Columbia (Autor:in)
  • Clara Moreau - , University of Montreal (Autor:in)
  • Lasse Bang - , Folkehelseinstituttet (FHI) (Autor:in)
  • Federico D’Agata - , University of Turin (Autor:in)
  • Giovanni Abbate-Daga - , University of Turin (Autor:in)
  • Christian K. Tamnes - , University of Oslo, Diakonhjemmet Hospital (Autor:in)
  • Iain Campbell - , King's College London (KCL) (Autor:in)
  • Owen O’Daly - , King's College London (KCL) (Autor:in)
  • Ulrike Schmidt - , King's College London (KCL) (Autor:in)
  • Guido Frank - , University of California at San Diego (Autor:in)
  • Stefanie Horndasch - , Universität Bielefeld, Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Andreas Hess - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Arnd Dörfler - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Hans Christoph Friederich - , Universität Heidelberg (Autor:in)
  • Joe Simon - , Universität Heidelberg (Autor:in)
  • Angela Favaro - , Università degli studi di Padova (Autor:in)
  • Luca Lavagnino - , University of Texas Health Science Center at Houston (Autor:in)
  • Christina E. Wierenga - , University of California at San Diego (Autor:in)
  • Amanda Bischoff-Grethe - , University of California at San Diego (Autor:in)
  • Amy E. Miles - , University of Toronto (Autor:in)
  • Allan Kaplan - , University of Toronto (Autor:in)
  • Aristotle Voineskos - , University of Toronto (Autor:in)
  • Paul A.M. Smeets - , Utrecht University, Wageningen University & Research (WUR) (Autor:in)
  • Annemarie A. van Elburg - , Altrecht Mental Health Institute, Utrecht University (Autor:in)
  • Unna Danner - , Altrecht Mental Health Institute, Utrecht University (Autor:in)
  • Sophia I. Thomopoulos - , Keck School of Medicine at University of Southern California (Autor:in)
  • Laura Berner - , Icahn School of Medicine at Mount Sinai (Autor:in)
  • Neda Jahanshad - , Keck School of Medicine at University of Southern California (Autor:in)
  • Sophia Frangou - , University of British Columbia, Icahn School of Medicine at Mount Sinai (Autor:in)
  • Joseph A. King - , Psychosoziale Medizin und Entwicklungsneurowissenschaften (Autor:in)
  • Paul Thompson - , Keck School of Medicine at University of Southern California (Autor:in)
  • Stefan Ehrlich - , Psychosoziale Medizin und Entwicklungsneurowissenschaften, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie (Autor:in)

Abstract

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/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. Mega-analyses reinforced previous meta-analytic findings of pronounced and widespread GM deficits in AN compared to HC. Normative modelling revealed that the frequency of infranormal z-scores (23/68 cortical thickness, 13/14 subcortical volume metrics) and supranormal z-scores (35/68 cortical thickness, 17/68 cortical surface area metrics) was significantly higher in AN than expected based on reference data. Individuals with AN could be reliably differentiated from HC using machine-learning classifiers (ROC–AUC = 0.75–0.81). In contrast, neither group-level differences nor frequency of extreme z-scores differed between AN subtypes, and individuals with different subtypes could not be reliably differentiated from each other. Importantly, the observational design cannot distinguish neurobiological differences related to AN from the effects of starvation or low BMI in the AN versus HC analyses. The lack of differences between subtypes does not exclude brain structural differences between AN subtypes that might be detectable with other modalities or analytic approaches. 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.

Details

OriginalspracheEnglisch
Aufsatznummere1004809
Seitenumfang20
FachzeitschriftPLoS medicine
Jahrgang23
Ausgabenummer5
PublikationsstatusVeröffentlicht - 20 Mai 2026
Peer-Review-StatusJa

Externe IDs

PubMed 42160333
ORCID /0000-0003-2132-4445/work/222089360
ORCID /0000-0002-2864-5578/work/222089366
ORCID /0000-0001-8029-8270/work/222089416
ORCID /0000-0002-5112-405X/work/222089469
ORCID /0000-0002-5413-0359/work/222089818

Schlagworte

ASJC Scopus Sachgebiete