Development of Neural Mechanisms Underlying Threat Processing: Associations With Childhood Social Reticence and Adolescent Anxiety

Anita Harrewijn*, Sonia G. Ruiz, Rany Abend, Simone P. Haller, Anni R. Subar, Caroline Swetlitz, Emilio A. Valadez, Melissa A. Brotman, Gang Chen, Andrea Chronis-Tuscano, Ellen Leibenluft, Yair Bar-Haim, Nathan A. Fox, Daniel S. Pine

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Social reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety. Methods: In this 16-year longitudinal study, social reticence was assessed from 2 to 7 years of age; anxiety symptoms and neural mechanisms during the dot-probe task were assessed at 10, 13, and 16 years of age. The sample included 144 participants: 71 children provided data at age 10 (43 girls, meanage = 10.62), 85 at age 13 (46 girls, meanage = 13.25), and 74 at age 16 (36 girls, meanage = 16.27). Results: A significant interaction manifested among social reticence, anxiety symptoms, and time, on functional connectivity between the left amygdala and the left dorsolateral prefrontal cortex, voxelwise p < .001, clusterwise familywise error p < .05. Children with high social reticence showed a negative association between amygdala–dorsolateral prefrontal cortex connectivity and anxiety symptoms with age, compared to children with low social reticence, suggesting distinct neurodevelopmental pathways to anxiety. Conclusions: These findings were present across all conditions, suggesting task-general effects in potential threat processing. Additionally, the timing of these neurodevelopmental pathways differed for children with high versus low social reticence, which could affect the timing of effective preventive interventions.

Original languageEnglish
JournalBiological Psychiatry Global Open Science
StateAccepted/In press - 2023


  • Adolescence
  • Anxiety
  • Functional connectivity
  • Social reticence
  • Threat processing
  • fMRI


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