Dynamic Amygdala Nuclei Alterations in Relation to Weight-Status in Anorexia Nervosa Are Mediated by Leptin

The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, we found differential amygdala nuclei alterations in acute anorexia nervosa (AN): Rostral-medial nuclei involved in fear/reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here we investigated longitudinal amygdala nuclei alterations in AN in relation to weight-status and their associations with leptin levels.T1-weighted structural MRI scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before/after short-term weight-restoration (N=110, >14% BMI-increase over three months) and female individuals with a history of AN (N=79, long-term [mean=5 years] weight-recovered) were compared to female healthy control participants (N=271) using linear mixed effects models.Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight-restoration (Cohen's d range=0.17-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions and anterior amygdaloid areas were only partially normalized following short-term weight-restoration. Right anterior amygdaloid area remained reduced after long-term weight-recovery compared to control participants (d=0.36). Leptin increase, accompanying short-term weight-restoration, mediated the effect of weight-gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei.Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during/after short-term weight-restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN.We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.