Adrenarcheal Timing Longitudinally Predicts Anxiety Symptoms via Amygdala Connectivity During Emotion Processing

Objective: This study aimed to examine longitudinally whether adrenarcheal timing (adrenarcheal hormone levels independent of age) and tempo (change in hormone levels over time) were associated with amygdala functional connectivity and how this in turn related to anxiety symptoms in the transition from childhood to adolescence. Method: Participants were 64 children (34 girls) who completed the Spence Children's Anxiety Scale and saliva collections to measure levels of testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate at rwo time points (mean age 9.5 years at time 1 [T1], 12.2 years at time 2 [T2]). Participants also viewed fearful and calm facial expressions while undergoing functional magnetic resonance imaging scanning at both time points. Amygdala functional connectivity was assessed with psychophysiological interaction analysis and modeled longitudinally with the Multivariate and Repeated Measures MATLAB toolbox. Results: Controlling for age, higher dehydroepiandrosterone sulfate at T1 was related to an increase in amygdala to inferior frontal gyrus connectivity over time (T1 to T2) in boys, but the opposite pattern was found in girls. Dehydroepiandrosterone at T1 showed a positive association with amygdala connectivity to several lateral prefrontal areas and the anterior cingulate across time. Higher dehydroepiandrosterone at T1 was indirectly related to more anxiety symptoms at T2, controlling for symptoms at T1, via more positive amygdala to inferior frontal gyrus connectivity. Changes in hormone levels did not relate to changes in amygdala connectivity (from T1 to T2). Conclusion: The results suggest that amygdala to prefrontal cortex connectivity may be a mechanism through which early adrenarcheal timing predicts the development of anxiety symptoms during adrenarche.