Differential alterations of amygdala nuclei volumes in acutely ill patients with anorexia nervosa and their clinical and neuroendocrine associations

Anorexia nervosa (AN) is a severe psychiatric disorder that predominantly affects girls and young women during adolescence. Patients with acute AN show symptoms indicative of limbic dysregulation including high depressive and anxious symptom levels as well as altered reward sensitivity. The amygdala is a subcortical limbic structure involved in the regulation of fear and reward processing and consisting of histologically and functionally distinct subregions. New automated structural MRI segmentation tools facilitate the in vivo study of individual amygdala nuclei in clinical populations. This study investigates amygdala nuclei volumes in AN, their potential clinical relevance and relationship with leptin levels, a key indicator of AN-related neuroendocrine alterations.

Methods

Processing of T1-weighted MRI scans comprised amygdala subsegmentation using FreeSurfer and multi-stage quality control. Left and right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (n=168, 12–29 years) and age-matched healthy females (n=168) applying general linear model approaches. Associations with leptin, BMI, illness duration, and psychiatric symptoms were analyzed via robust linear regression.

Results

Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN relative to HC. More importantly, three specific nuclei (accessory basal, cortical nucleus, and corticoamygdaloid transition in the rostral-medial amygdala) showed greater bilateral volumetric reduction in AN relative to the reduction of whole amygdala and total subcortical gray matter volumes. Basal, lateral, and paralaminar nuclei were relatively less reduced. All nuclei volumes within the rostral-medial cluster were positively associated with leptin levels above and beyond BMI effects.

Conclusions

In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory and food-related reward processing, may represent a structural correlate of AN-related psychopathology. Hypoleptinemia might be linked to these rostral-medial amygdala alterations.