Associations between adrenarcheal hormones, amygdala functional connectivity and anxiety symptoms in children

Objective: The transition from childhood to adolescence is a vulnerable period for the development of anxiety
symptoms. There is some evidence that hormonal changes occurring during adrenarche, an early pubertal phase,
might play a role in this increased vulnerability. Little is known about underlying brain mechanisms. Given the
role of the amygdala-based fear circuit in anxiety, the current study aimed to investigate whether children’s
adrenarcheal hormone levels were associated with functional connectivity of the amygdala while processing
fearful facial expressions, and how this in turn related to anxiety symptoms.
Method: Participants were 83 children (M age 9.53 years) who completed two morning saliva collections to
measure levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS), and testosterone. They also completed
the Spence Children’s Anxiety Scale (SCAS), and viewed fearful and calm facial expressions while undergoing a
functional MRI scan. Psychophysiological interaction (PPI) analyses were performed to examine amygdala
connectivity and significant clusters were fed into a bootstrapping mediation model.
Results: In boys, mediation analyses showed an indirect positive effect of testosterone on anxiety symptoms,
which was mediated by amygdala-secondary visual cortex connectivity as well as amygdala-anterior cingulate
connectivity. In girls, DHEAS showed a negative indirect association with anxiety symptoms mediated by
amygdala connectivity to the fusiform face area and insula.
Conclusion: The results indicate unique roles for adrenarcheal hormones in anxiety and suggest that amygdala
connectivity may represent an important neural mechanism in these associations. Importantly, results reveal
prominent sex differences in the biological mechanisms associated with anxiety in children undergoing adrenarche.