Dynamic Structural Brain Changes in Anorexia Nervosa: A Replication Study, Mega-analysis, and Virtual Histology Approach

Bahnsen, Klaas; Bernardoni, Fabio; King, Joseph A.; Geisler, Daniel; Weidner, Kerstin; Roessner, Veit; Patel, Yash; Paus, Tomáš; Ehrlich, Stefan

doi:10.1016/j.jaac.2022.03.026

Cited by 24 publications

(53 citation statements)

References 54 publications

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“…Group comparisons revealed significantly increased levels of NF-L, tau protein, and GFAP in acAN-TP1 compared to HC. As expected and shown in our previous studies (Bahnsen et al, 2022;Bernardoni et al, 2016), acAN-TP1 showed widespread reductions in CT (online Supplementary Fig. S1).…”

Section: Study Sample and Clinical Measuressupporting

confidence: 91%

“…Speculatively, the differential relationships found between the investigated markers and CT might be due to their different origins: NF-L is abundant in large-caliber myelinated axons (Gaetani et al, 2019;Zetterberg et al, 2013), while tau protein is predominantly expressed in thin non-myelinated axons of cortical interneurons (Trojanowski et al, 1989;Zetterberg et al, 2013). In line with this, a recent study found that CT reductions in AN are more prevalent in regions with greater structural and functional connectivity to other brain regions ('hubs'; Bahnsen et al, 2022). Neuronal damage or remodeling processes occurring in the acutely underweight state of AN (Hellerhoff et al, 2021;King et al, 2018;Nilsson et al, 2019) might thus be more pronounced in these regions.…”

Section: Psychological Medicinementioning

confidence: 89%

“…The additional HC group consisted of 149 female participants (age range 12-23 years) of whom two were excluded after quality control (final sample of 147 HC participants). The sample partially overlaps with our previous studies (Bahnsen et al, 2022;Bernardoni et al, 2016;Hellerhoff et al, 2021; see online Supplementary Information 1.1 for Details). AN patients were studied in the acutely underweight state (acAN-TP1) not more than 96 h after admission to intensive treatment and reassessed after short-term partial weight restoration (acAN-TP2; after an a priori-defined minimum BMI increase of 10%; all patients in the present sample had a BMI increase >14%).…”

Section: Participantsmentioning

confidence: 99%

“…Each participant's T1-weighted MP-RAGE images were first preprocessed in an automated manner with the FreeSurfer software suite (https://surfer.nmr.mgh.harvard.edu/; version 5.3; Desikan et al 2006;Fischl & Dale, 2000;Fischl et al 2002Fischl et al , 2004. Thereafter quality control (online Supplementary Information 1.4.2) was carried out as described in our previous studies (Bahnsen et al, 2022;Bernardoni et al, 2016;Reuter, Schmansky, Rosas, & Fischl, 2012). All images underwent further longitudinal preprocessing with the FreeSurfer longitudinal stream.…”

Section: Mri Acquisition and Processing And Ct Estimationmentioning

confidence: 99%

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Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa

et al. 2023

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Background Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN. Methods Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n = 147). Results In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected. Conclusions A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.

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Section: Study Sample and Clinical Measuressupporting

confidence: 91%

Section: Psychological Medicinementioning

confidence: 89%

Section: Participantsmentioning

confidence: 99%

Section: Mri Acquisition and Processing And Ct Estimationmentioning

confidence: 99%

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Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa

et al. 2023

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“…In acute AN, we recently showed that leptin levels predicted the severity of volumetric reductions in rostral‐medially clustered nuclei within the amygdaloid complex independent of body mass index (BMI) 29 . In contrast to well‐known global gray matter reductions in AN, 13,18–20,30–33 within‐amygdala alterations were subregion‐specific, involving accessory basal, cortical, medial nuclei, and corticoamygdaloid transition volumes, clustered in the rostral‐medial amygdala 29 . Additionally, according to research in rodents, these rostral‐medial amygdala nuclei are densely equipped with leptin receptors 34 and play roles in the evaluation of the emotional valence of gustatory, olfactory, and visual stimuli, fear and reward learning, and long‐term memory formation from affective information 10–13 .…”

Section: Introductionmentioning

confidence: 99%

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa

Wronski,

Hohnemann,

Bernardoni

et al. 2023

Acta Psychiatr Scand

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ObjectiveThe amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral‐medial cluster substantially affected) and, in another study, elevated food−/weight‐related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN‐related rumination and potentially mediate the leptin‐rumination relationship in AN.MethodsRumination (food−/weight‐related) was assessed using ecological momentary assessment for a 14‐day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12–29 years, majority admitted to inpatient treatment) and age‐matched healthy females (n = 51) to investigate associations between rostral‐medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi‐level structural equation models.ResultsReduced right accessory basal and cortical nuclei volumes predicted more frequent weight‐related rumination in AN; both nuclei fully mediated the effect of leptin on weight‐related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females.ConclusionThis study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

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Hypothalamic subregion alterations in anorexia nervosa and obesity: Association with appetite‐regulating hormone levels

Alzaid,

Simon,

Brugnara

et al. 2024

Intl J Eating Disorders

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ObjectiveAnorexia nervosa (AN) and obesity are weight‐related disorders with imbalances in energy homeostasis that may be due to hormonal dysregulation. Given the importance of the hypothalamus in hormonal regulation, we aimed to identify morphometric alterations to hypothalamic subregions linked to these conditions and their connection to appetite‐regulating hormones.MethodsStructural magnetic resonance imaging (MRI) was obtained from 78 patients with AN, 27 individuals with obesity and 100 normal‐weight healthy controls. Leptin, ghrelin, and insulin blood levels were measured in a subsample of each group. An automated segmentation method was used to segment the hypothalamus and its subregions. Volumes of the hypothalamus and its subregions were compared between groups, and correlational analysis was employed to assess the relationship between morphometric measurements and appetite‐regulating hormone levels.ResultsWhile accounting for total brain volume, patients with AN displayed a smaller volume in the inferior‐tubular subregion (ITS). Conversely, obesity was associated with a larger volume in the anterior‐superior, ITS, posterior subregions (PS), and entire hypothalamus. There were no significant volumetric differences between AN subtypes. Leptin correlated positively with PS volume, whereas ghrelin correlated negatively with the whole hypothalamus volume in the entire cohort. However, appetite‐regulating hormone levels did not mediate the effects of body mass index on volumetric measures.ConclusionOur results indicate the importance of regional structural hypothalamic alterations in AN and obesity, extending beyond global changes to brain volume. Furthermore, these alterations may be linked to changes in hormonal appetite regulation. However, given the small sample size in our correlation analysis, further analyses in a larger sample size are warranted.Public SignificanceUsing an automated segmentation method to investigate morphometric alterations of hypothalamic subregions in AN and obesity, this study provides valuable insights into the complex interplay between hypothalamic alterations, hormonal appetite regulation, and body weight, highlighting the need for further research to uncover underlying mechanisms.

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Dynamic Structural Brain Changes in Anorexia Nervosa: A Replication Study, Mega-analysis, and Virtual Histology Approach

Cited by 24 publications

References 54 publications

Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa

Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa

Hypothalamic subregion alterations in anorexia nervosa and obesity: Association with appetite‐regulating hormone levels

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