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

Abstract

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.

Keywords: BMI; Cortical thickness; MRI; Subcortical volume; Surface area.

Figure 1.

Subcortical volume reductions in anorexia nervosa. Differences (Cohen’s d) between A) patients with Anorexia Nervosa (AN) and healthy controls (HC₂) and B) all groups, including acute (acAN) and partially weight-restored patients (pwrAN). Color scale: Warmer colors indicate lower volumes (Cohen’s d; averaged across the left and right hemispheres, but depicted on the right side of the brain) in patients compared to controls. Error bars are 95% confidence intervals.

Figure 2.

Reductions in A) cortical thickness and B) surface area between patients with Anorexia Nervosa (AN) and healthy controls (HC₂). Results, which are uncorrected for global measures, are shown on the left in each panel. Results, which are corrected for global measures, are shown on the right in each panel. Color scale: Warmer colors indicate reductions (Cohen’s d effect size; averaged across the left and right hemispheres, but depicted on the right side of the brain) in patients compared to controls.

Figure 3.

Pairwise reductions, shown as Cohen’s d effect sizes, in A) cortical thickness and B) surface area between acute patients with Anorexia Nervosa (acAN), partially weight-restored patients (pwrAN) and healthy controls (HC₃). Color scale: Warmer colors indicate reductions (Cohen’s d; averaged across the left and right hemispheres, but depicted on the right side of the brain).

Figure 4.

Neural contextualization of cortical thickness case-control differences. Cohen’s d effect sizes in the context of: A) regional cytoarchitecture, specifically overall cellular density (A; top panel) and laminar differentiation (A; lower panel); B) cytoarchitectonic classes based on postmortem work by von Economo and Koskinas; and degree centrality according to C) functional and D) structural connectivity.