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Amygdala Subregional Structure and Intrinsic Functional Connectivity Predicts Individual Differences in Anxiety During Early Childhood
Open accessAbstract
Background Early childhood anxiety has been linked to an increased risk for developing mood and anxiety disorders. Little, however, is known about its effect on the brain during a period in early childhood when anxiety-related traits begin to be reliably identifiable. Even less is known about the neurodevelopmental origins of individual differences in childhood anxiety.Methods We combined structural and functional magnetic resonance imaging with neuropsychological assessments of anxiety based on daily life experiences to investigate the effects of anxiety on the brain in 76 young children. We then used machine learning algorithms with balanced cross-validation to examine brain-based predictors of individual differences in childhood anxiety.Results Even in children as young as ages 7 to 9, high childhood anxiety is associated with enlarged amygdala volume and this enlargement is localized specifically to the basolateral amygdala. High childhood anxiety is also associated with increased connectivity between the amygdala and distributed brain systems involved in attention, emotion perception, and regulation, and these effects are most prominent in basolateral amygdala. Critically, machine learning algorithms revealed that levels of childhood anxiety could be reliably predicted by amygdala morphometry and intrinsic functional connectivity, with the left basolateral amygdala emerging as the strongest predictor.Conclusions Individual differences in anxiety can be reliably detected with high predictive value in amygdala-centric emotion circuits at a surprisingly young age. Our study provides important new insights into the neurodevelopmental origins of anxiety and has significant implications for the development of predictive biomarkers to identify children at risk for anxiety disorders.
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“Findings in the amygdala regions for anxious vs. non-anxious adolescents are less clear, with some studies reporting larger volumes in the right and left amygdala, specifically the basolateral amygdala35,36, smaller volumes in the left amygdala31,37,38 or no difference in amygdala volume39.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [36]
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“Altogether, our findings suggest that amygdala hyperconnectivity in anxious children has a neuroanatomical profile similar to those seen in adults with high anxiety (17,18) or anxiety disorders (39,46).”
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Metadata
- Authors
- Qin, S., Young, C. B., Duan, X., Chen, T., Supekar, K., & Menon, V.
- Affiliations
- Stanford Medicine (US)
- Northwestern University (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 75
- Issue
- 11
- Pages
- 892-900
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3984386
- OpenAlex
- W2009779345
- Cited by
- 249
- References
- 64
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 21 · 2023: 26 · 2022: 20 · 2021: 30 · 2020: 29 · 2019: 20 · 2018: 20 · 2017: 24 · 2016: 18 · 2015: 18 · 2014: 9
- FWCI
- 16.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001085)
- National Institute of Mental Health (MH084164, R01MH084164)
- National Center for Research Resources (UL1RR025744)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD057610, HD047520, HD059205, R01HD047520, R01HD059205)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- childhood anxiety, amygdala, basolateral amygdala, amygdala volume, intrinsic functional connectivity, individual differences, brain development, emotion regulation, predictive biomarkers, early childhood
- MeSH terms
- Amygdala, Anxiety, Brain Mapping, Child, Female, Humans, Magnetic Resonance Imaging, Male, Psychological Tests
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