Exploring Gray–White Matter Contrast in Anorexia Nervosa: A Structural MRI Study

Background: Anorexia nervosa (AN) is a severe psychiatric disorder characterized by self-imposed starvation, intense fear of weight gain, and distorted body image. Beyond its profound psychological impact, chronic malnutrition induces structural brain changes, including reductions in gray- and white-matter volumes. Gray–white matter contrast (GWC) derived from T1-weighted MRI has emerged as an indirect marker of intracortical myelin and tissue integrity but has not yet been examined in AN. Aim of the Study: This study sought to characterize vertex-wise differences in cortical GWC between adolescents and young adults with AN and age-matched healthy controls (HC). A secondary goal was to compare these GWC findings with conventional cortical thickness (CT) measures and to explore their relationships with clinical severity indices. Materials and Methods: A cross-sectional sample of 58 female participants (29 AN; 29 HC) aged 14–34 years was recruited. High-resolution T1-weighted images were acquired on a 3 T scanner and processed with FreeSurfer 7.4.1. GWC maps were computed at each cortical vertex as the percent signal contrast between adjacent white and gray matter, then smoothed (15 mm FWHM) and projected to the fsaverage template. Vertex-wise general linear models assessed group differences in GWC under two conditions: (1) controlling for age only, and (2) controlling for age and vertex-wise CT. A separate model tested CT differences controlling for age. Cluster-wise correction for multiple comparisons used Monte Carlo simulation (cluster‐forming threshold |t| > 2.00, cluster‐wise p < 0.05). Within the AN group, Spearman correlations related mean GWC in significant clusters to BMI at scan, age of onset, and illness duration. Results: In the age-only GWC model, two clusters in the left hemisphere showed significantly higher GWC in AN compared to HC, namely the inferior temporal cortex (cluster size 1,386.7 mm²; peak MNI coordinates –43.1, –11.5, –36.9; CWP = 0.002) and the medial orbitofrontal cortex (cluster size 860.8 mm²; peak MNI coordinates –8.7, 48.2, –9.9; CWP = 0.030). In the model controlling for both age and vertex-wise CT, no clusters survived correction despite unthresholded maps qualitatively resembling the age-only pattern. Analysis of cortical thickness revealed no significant group differences after correction, with unthresholded maps showing minimal divergence. Finally, within the AN group, mean GWC in each cluster did not correlate significantly with BMI at scan, age of onset, or illness duration. Conclusions: Patients with AN exhibit focal increases in cortical GWC, most prominently in the left medial orbitofrontal and inferior temporal cortices, despite the absence of detectable cortical thinning. These findings suggest that malnutrition-related microstructural changes (e.g., reduced intracortical myelin, fluid shifts) may sharpen the gray–white boundary on T1-weighted MRI. The elimination of GWC differences when adjusting for CT likely reflects shared variance rather than true absence of effect, underscoring GWC’s complementary sensitivity to tissue properties beyond morphometry. Lack of correlations with clinical indices may be due to limited sample size and the cross-sectional design. Future longitudinal and multimodal studies are warranted to determine whether GWC alterations serve as state markers of malnutrition or reflect trait vulnerabilities, and to evaluate their reversibility with weight restoration.