In relation to anxiety severity, puberty moderates functional connectivity between the amygdala and anterior...

Anxiety symptoms often escalate in peri-adolescence (ages 10-13 years), a sensitive period when puberty-related changes occur in neural systems implicated in psychopathology. Greater amygdala activation and altered functional connectivity with the medial prefrontal cortex (mPFC) in response to negative stimuli have been associated with higher anxiety levels. Still, how puberty influences the relationship between neural functioning and anxiety symptoms remains unclear. In this study, we investigated whether pubertal status moderated the associations of amygdala activation and functional connectivity with mPFC subregions and anxiety symptom severity in 144 peri-adolescents spanning from typical to clinical severity. Participants viewed complex negative and neutral images (i.e., scenes) during an fMRI task. General linear models assessed the effects of pubertal status, amygdala activation, mPFC functional connectivity, and age on anxiety severity. We found a significant interaction between pubertal status and the difference in connectivity between the amygdala and the anterior cingulate cortex (ACC), a ventral mPFC subregion, in the negative versus neutral condition (p = .009), with evidence of a negative relationship that was greatest in more pubertally mature participants. We also observed a significant negative association between amygdala-ACC connectivity and anxiety severity for negative stimuli (p = .037). While results demonstrated negative stimuli elicited greater amygdala activation than neutral stimuli (p < .001), this difference was not moderated by pubertal status or associated with anxiety severity. Our results suggest that middle-to-late puberty is a critical window where amygdala-ACC connectivity is more strongly associated with anxiety severity, particularly for negative compared to neutral stimuli.