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

Objective: 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 (7T) fMRI.Method: 25 (13 female) 12-17 years-old adolescents and 44 (31 male) 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).Results: Contrary to hypotheses, amygdala activity in the Worry condition was positively correlated with age. In partial confirmation of hypotheses, female participants had elevated Worry – Neutral PVN activity (driven by lower Neutral activity), but elevated amygdala-vmPFC connectivity during Reappraisal than male participants. In exploratory analyses, female participants had elevated amygdala-PVN connectivity during Reappraisal compared to male participants. Conclusion: Adolescents utilize less amygdala-centered networks during worry than adults, suggesting that interventions designed for adults may not translate directly to adolescents. Female individuals show increased PVN recruitment and amygdala-PVN activity during worry, which could predispose them to more somatic symptoms of anxiety. Results may inform clinical presentation and interventions for anxiety disorders.