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

doi:10.1016/j.bpsgos.2023.01.008

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

Biol Psychiatry Glob Open Sci. 2023 Feb 3;3(4):893-901. doi: 10.1016/j.bpsgos.2023.01.008. eCollection 2023 Oct.

Authors

Anita Harrewijn^{1

2}, Sonia G Ruiz¹, Rany Abend^{1

3}, Simone P Haller¹, Anni R Subar⁴, Caroline Swetlitz⁵, Emilio A Valadez⁶, Melissa A Brotman¹, Gang Chen⁷, Andrea Chronis-Tuscano⁸, Ellen Leibenluft¹, Yair Bar-Haim⁹, Nathan A Fox⁶, Daniel S Pine¹

Affiliations

¹ Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
² Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands.
³ School of Psychology, Reichman University, Herzliya, Israel.
⁴ Department of Psychology, University of Denver, Denver, Colorado.
⁵ Department of Psychology, Boston University, Boston, Massachusetts.
⁶ Department of Human Development and Quantitative Methodology, University of Maryland, College Park, Maryland.
⁷ Scientific and Statistical Computing Core, National Institute of Mental Health, Bethesda, Maryland.
⁸ Department of Psychology, University of Maryland, College Park, Maryland.
⁹ School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.

Abstract

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, mean_age = 10.62), 85 at age 13 (46 girls, mean_age = 13.25), and 74 at age 16 (36 girls, mean_age = 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.

Keywords: Adolescence; Anxiety; Functional connectivity; Social reticence; Threat processing; fMRI.

Abstract

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