Effects of sex, pubertal stage, and pubertal hormones on frontal and limbic responses to fearful and happy faces during early adolescence.

Adolescence is a key stage of brain development marked by heightened emotional reactivity, with variability across individuals and sexes. Puberty onset also initiates a cascade of changes that influence how the brain responds to social-emotional information. To more fully characterize the role of sex and puberty in the brain's response to social-emotional cues during early adolescence, we tested the main and interactive effects of sex, pubertal stage, and pubertal hormone levels on neural activation to negative and positive facial expressions. Combining baseline and 2-year follow-up data from the Adolescent Brain Cognitive DevelopmentSM study (N = 13,182 observations at two timepoints; 53% male; ages 9-13), we examined neural activation to fearful and happy faces (vs. neutral faces) in the amygdala, anterior cingulate cortex (ACC), ventrolateral prefrontal cortex, ventromedial prefrontal cortex, and dorsolateral prefrontal cortex engaged during an emotional n-back fMRI task. Pubertal development was assessed via parent-report of the child's pubertal stage and salivary hormone levels additionally indexed maturational changes from puberty beyond stage-based milestone achievements. A significant pubertal stage × estradiol interaction was found on ACC activation to happy faces among girls, indicating that estradiol level was positively associated with ACC activation in prepubertal girls but negatively in late-pubertal girls. No significant main effects of sex, puberty stage or hormone levels, or any other interactions withstood multiple comparison correction. These findings suggest estradiol's effects on neural processing of positive social-emotional cues change across puberty among girls and may signify hormone-related shifts from emotional reactivity to regulation in the brain.