(PS9-D83) Sex Differences in the Relationship Between Adolescent Anxiety Sensitivity and Brain Circuits Related to Emotion Regulation

Introduction: Adolescence is a tumultuous developmental period marked by significant social and biological changes, as well as the onset of internalizing pathologies such as anxiety. Moreover, females are disproportionately affected, and these differences emerge or widen in adolescence. Previous research has linked the onset of pathological anxiety in adolescence to deficits in emotion regulation, but the mechanisms that contribute to these differences in emotion regulation remain understudied. The current study uses fMRI to examine sex differences in the relationship between anxiety sensitivity and circuits involved in emotion regulation. 

Methods: 66 adolescents (M/SDage= 12.23/.97; 51.5% female) completed the Childhood Anxiety Sensitivity Index (CASI; M/SD = 28.42/6.28), a self-report measure of sensitivity to anxiety-related physiological sensations (e.g., heart rate). Adolescents also performed an emotion regulation behavioral task during an fMRI scan. Initial analyses examined the relationship between CASI, regulation condition (regulate emotion vs. react), and stimulus valence (negative vs. neutral). Finally, we examined the moderating role of biological sex on these relationships. 

Results: Initial analyses revealed significant clusters in left Brodmann areas 6 and 8 in which CASI moderated neural responses to regulation demands. Specifically, higher CASI was linked to greater activation during regulate but not react. Analyses also revealed clusters in which biological sex moderated the relationship between CASI and neural responses to the stimulus valence. Specifically, higher CASI was linked to greater activation in right agranular orbitofrontal cortex when encountering negative (but not neutral) stimuli, and this was only observed in females. Conversely, higher CASI was associated with weaker activation in frontal pole (BA 10) when viewing negative (but not neutral) stimuli, and this was only observed in males.  

Discussion: Our results provide novel insight into sex differences in the relationship between anxiety sensitivity and emotion regulation during adolescence. Results from regulation contrasts suggest increased activation of left Brodmann areas 6 and 8 were specific to engagement in regulation, indicating those with higher anxiety sensitivity recruit more from these regions. Additionally, findings suggest risk for anxiety symptomatology for female adolescents may be specifically related to heightened activation in response to negative stimuli. Furthermore, increased activation of left medial frontal gyrus may serve as a risk factor for developmental deficits in regulatory capacity. Etiological and clinical implications of anxiety pathology development will be further discussed.