BACKGROUND: Anorexia nervosa (AN) is a mental disorder characterized by dietary restriction, fear of gaining weight, and distorted body image. Recent studies indicate the hippocampus, crucial for learning and memory, may be affected in AN, yet subfield-specific effects remain unclear. Here we investigated hippocampal subfield alterations in acute AN, changes following weight-restoration and their associations with leptin levels.

METHODS: T1-weighted magnetic resonance imaging scans were processed using FreeSurfer. We compared 22 left and right hemispheric hippocampal subfield volumes cross-sectionally and longitudinally in females with acute AN (n = 165 at baseline, n = 110 after partial weight-restoration), healthy females (n = 271, HC), and females after long-term recovery from AN (n = 79) using linear models.

RESULTS: We found that most hippocampal subfield volumes were significantly reduced in AN compared to HC (~ - 3.9%). Certain areas like the subiculum exhibited no significant reduction in the acute state of AN, while other areas, like the hippocampal tail, showed strong decreases (~ - 9%). Following short-term weight-recovery, most subfields increased in volume. Comparisons between participants after long-term weight-recovery and HC yielded no differences. The hippocampal tail volume was positively associated with leptin levels in AN independent of BMI.

CONCLUSIONS: Our study provides evidence of differential volumetric differences in hippocampal subfields between individuals with AN and HC and almost complete normalization after weight rehabilitation. These alterations are spatially inhomogeneous and more pronounced compared to other major mental disorders (e.g., major depressive disorder, schizophrenia). We provide novel insights linking hypoleptinemia to hippocampal subfield alterations hinting towards clinical relevance of leptin normalization in AN recovery. This article is protected by copyright. All rights reserved.