Amygdala Subregion Volumes and Apportionment in Preadolescents - Associations with Age, Sex, and Body Mass Index

Importance: The amygdala, a key limbic structure, plays a critical role in emotional, social, and appetitive behaviors that develop throughout adolescence. Composed of a heterogeneous group of nuclei, questions remain about potential differences in the maturation of its subregions during development.

Objective: To characterize the associations between developmental variables and amygdala subregion volumes during preadolescence.

Design setting and participants: Cross-sectional Adolescent Brain Cognitive Development (ABCD^®) Study data was collected from 3,953 9- and 10-year-old children between September 1, 2016, and October 15, 2018. Data analysis was conducted between June 1, 2023, and July 30, 2024.

Main outcomes and measures: Using the CIT168 Amygdala Atlas, nine amygdala subregion volumes were quantified from high-quality MRI scans. Linear mixed-effects models were used to examine the effects of age, sex, pubertal stage, and body mass index z-score (BMIz) on subregion volumes and their relative apportionment within the amygdala.

Results: The study population consisted of 3,953 preadolescents (mean [SD] age, 120 [7.41] months; 1,763 [44.6%] female; 57 [1.4%] Asian, 527 [13.3%] Black, 740 [18.7%] Hispanic, 2,279 [57.7%] white, and 350 [8.9%] from other racial/ethnic groups [identified by parents as American Indian/Native American, Alaska Native, Native Hawaiian, Guamanian, Samoan, other Pacific Islander, or other race]). Distinct associations were observed between age, sex, and BMIz and whole amygdala volume, subregion volumes, and subregion apportionment. Pubertal stage was not related to amygdala subregion volumes. Age was associated with near-global expansion of amygdala subregions during this developmental period. Female sex was linked to smaller volumes in most amygdala subregions, with larger relative apportionment in dorsal amygdala subregions and smaller apportionment in the basolateral ventral paralaminar subregion. Higher BMIz was associated with smaller volumes in large laterobasal subregions, with increased relative apportionment in smaller subregions.

Conclusions and relevance: This cross-sectional study suggests that age, but not pubertal stage, is associated with near-global expansion of the amygdala at ages 9 and 10, while sex and BMIz are linked to distinct changes in amygdala subregions that explain observed differences in total volumes. These findings provide a foundational context for understanding how developmental variables influence amygdala structure in preadolescents, with implications for understanding future risk for brain disorders.