Sex differences in the neural correlates of affective reactivity and regulation in early adolescence

Internalizing disorders are the leading cause of disability worldwide. Despite this public health crisis, borne disproportionately by female adolescents, specific neural mechanisms driving these differences remain unclear. The present study investigated sex differences in the neural circuitry underlying emotion regulation in a community sample of 180 early adolescents (M_age= 12.03 years; 54.4 % female). Participants were instructed to either react naturally or regulate their affective responses to negative or neutral stimuli. Voxelwise analyses revealed a significant 3-way interaction between sex, regulation (e.g., regulate vs. react), and stimulus valence (e.g., negative vs. neutral) in bilateral middle/medial orbitofrontal cortex (OFC), right middle frontal gyrus (MFG), and right amygdala. Specifically, female adolescents recruited bilateral OFC when asked to regulate their responses to aversive images. Recruitment of left (but not right) OFC was greater for male adolescents than female adolescents when regulating their responses to neutral stimuli. Finally, greater deactivation of right MFG was found when female adolescents reacted naturally to aversive stimuli, relative to male adolescents. These regions play critical roles in cognitive processes involved in emotion regulation. Our identification of sex-specific mechanisms supporting affective processes in early adolescents may reflect risk factors that can be intervened upon before the crystallization of internalizing pathology.