More similarity than difference: Comparison of within- and between-sex variance in early adolescent brain structure.

Abstract

Adolescent neuroimaging studies of sex differences in the human brain predominantly examine average differences between males and females. This focus on mean differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain. We aimed to characterize the variance in brain macro- and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11-year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N = 7,723). For global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within- and between-sex variance, overlap between male and female distributions, inhomogeneity of variance, effect size, and CLES. We examined these sex differences using both unadjusted (raw) brain estimates and residualized brain estimates from mixed-effects modeling (adjusted) to account for variance better attributed to age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable. Contrary to the popular view of the brain as sexually dimorphic, we found high similarity and low difference between sexes in all regional measurements of brain structure examined after accounting for other sources of variance. However, the sex difference for adjusted total brain volume (TBV) had a medium effect size and a 71.9% probability that a randomly chosen male adolescent would have a larger brain than a randomly chosen female adolescent. All cortical and subcortical volumes showed significant inhomogeneity of variance between sexes, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Previously reported sex differences in early adolescent regional human brain volume may, therefore, be driven by disparities in variance, rather than binary, sex-based phenotypes. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure.