Identifying neurodevelopmental signatures of worry: An ultra-high field (7-Tesla) fMRI study among adolescents and young adults

Worry plays an important role in anxiety disorders, but its neurodevelopment remains unclear. Worry increases during adolescence when cognitive-affective neural circuits are developing, impacting girls especially. Activity of and connectivity between amygdala and paraventricular nucleus (PVN) of the hypothalamus play an important role in anxiety symptoms, and amygdala-ventromedial prefrontal cortex (vmPFC) connectivity subserves emotion regulation. Here, we examined how functional changes in these circuits related to age, sex, and anxiety symptoms among adolescents and young adults using ultra-high field (7 T) fMRI. 25 (13 female) 12-17 years-old adolescents and 44 (31 female) 18-31 years-old young adults completed fMRI worry induction and reappraisal tasks previously used in adults. Brain activity was extracted from a priori regions of interest in amygdala, PVN and vmPFC, and connectivity was calculated using generalized psychophysiological interaction (gPPI). The task modulated worry as expected, but did not modulate amygdala activity or amygdala-vmPFC activity; however, PVN activity was elevated in Worry compared to Neutral, and amygdala-PVN connectivity was decreased in Reappraisal compared to Worry and Neutral. Contrary to hypotheses, no relationships were seen between amygdala activity or amygdala-vmPFC connectivity with sex or age. In exploratory analyses, female participants had elevated amygdala-PVN connectivity during Reappraisal compared to male participants. PVN and amygdala-PVN activity may be central to real-time worry, and Reappraisal appears to reduce amygdala-PVN connectivity. Female individuals show increased amygdala-PVN activity, which could predispose them to more somatic symptoms of anxiety. Results suggest that somatic-focused interventions may be beneficial for worry, especially in female individuals. • This study examined brain activity during worry in 69 individuals age 12-31. • Adolescents had less amygdala activity than adults, implying worry networks differ by age. • Females had more activity/connectivity in regions associated with somatic symptoms. • Treatment for anxiety disorders may benefit from tailoring by age and sex.