Differential longitudinal changes of hippocampal subfields in patients with anorexia nervosa

Abstract

BackgroundAnorexia 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.MethodsT1‐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.ResultsWe 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.ConclusionsOur 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.

Anorexia-Induced Hypoleptinemia Drives Adaptations in the JAK2/STAT3 Pathway in the Ventral and Dorsal Hippocampus of Female Rats

“…We believe that such alterations might contribute to driving the transition from adaptation to starvation toward maladaptive alterations that are still observed even when bodyweight is recovered. Our data could help explain the hippocampal-dependent structural and functional impairments observed in the ABA model (Mottarlini et al, unpublished data) [ 54 ] and in patients with AN [ 55 , 56 , 57 ].…”

“…Among the extra-hypothalamic regions in which leptin exerts its function, we focused our attention on the hippocampus since sizeable reductions in hippocampal subfield volumes have been observed in young, acutely underweight patients with AN and, even more interestingly, a larger reduction of these hippocampal subfields has been predicted by hypoleptinemia in the acute phase of the disorder [ 55 ]. We investigated the two main subregions of the Hip, dorsal and ventral, since they play different roles in regulating emotion, stress-related responses and cognitive processes.…”