BACKGROUND: Cortical folding is thought to remain relatively invariant after birth. Therefore, differences seen in psychiatric disorders have been proposed as early biomarkers or used as intermediate phenotypes in imaging genetics studies. Anorexia nervosa (AN) is associated with drastic and rapid structural brain alterations and thus may be an ideal model disorder to study environmental influences on cortical folding.

METHODS: To date, the only two studies in AN applied different methods (local gyrification index and mean curvature) and found seemingly discordant results. We computed both vertexwise measures in a sizable sample of acutely underweight female AN patients (n = 87, mean age 16.5 years), long-term recovered patients (n = 58, mean age 22 years), and healthy control participants (n = 141, mean age 19.5 years). The majority of acutely ill patients were scanned longitudinally (n = 57) again after partial weight normalization (>14% body mass index increase).

RESULTS: While gyrification was broadly reduced in acutely ill patients, normal values were restored in most brain regions after partial weight restoration (≈3 months), and after full recovery no significant differences were evident relative to control participants. Increased gyrification was largely predicted by weight restoration alone. Results for absolute mean curvature analyses complemented those obtained using the local gyrification index.

CONCLUSIONS: Together, these findings indicate that nutritional status affects cortical folding and suggest that gyrification studies may need to better control for environmental factors. Moreover, they provide novel support for the likelihood that macroscopic changes in the cortical organization in AN are more reflective of nutritional state than premorbid trait markers or permanent scars.