# Neural Origins of Temperamental Risk for Anxiety

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $231,750

## Abstract

Project Summary
Anxiety disorders affect one third of the US population, significantly burdening individuals and society.
Although rates peak in late adolescence, anxiety disorders have origins in infant and early childhood
temperament. Moreover, beyond predicting risk for later anxiety, early temperament even more strongly
predicts later neural correlates of anxiety. As such, temperament may identify an enduring neural “risk
signature.” Precisely characterizing this signature may generate knowledge that would help reduce the burden
of long-term mental health problems. However, most research quantifies such neural risk signatures in older
children and adults. Thus, it remains unclear whether such a risk signature, involving temperament and brain
function, manifests in infancy before predicting later behavior. Here, we propose to recruit a sample of typically
developing 3-5-month-old infants screened to identify negative reactive temperament, characterize their brain
networks using magnetic resonance imaging (MRI), and assess their Behavioral Inhibition (BI) at 13-15 months
of age. Our prior work uses novelty-evoked motor activity and behavioral distress to quantify a temperamental
bias called negative reactivity. This bias predicts later avoidance of unfamiliar stimuli or contexts during early
childhood, a pattern called BI. BI, in turn, is associated with functioning in the brain’s salience and ventral
attention networks. Moreover, BI is the best early-child behavioral predictor of later anxiety disorders,
conditions also associated with functioning in the salience and ventral attention networks. We will test the
hypothesis that behaviorally assessed negative reactivity in early infancy is associated with decreased
functional connectivity in the salience and ventral attention networks relative to non-reactive infants. Identifying
the neural underpinnings of heightened negative reactivity in infancy and links to BI will elucidate the
neurobiological origins of risk for the development of anxiety.

## Key facts

- **NIH application ID:** 10127236
- **Project number:** 1R21MH122976-01A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Nathan A Fox
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,750
- **Award type:** 1
- **Project period:** 2020-12-10 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127236

## Citation

> US National Institutes of Health, RePORTER application 10127236, Neural Origins of Temperamental Risk for Anxiety (1R21MH122976-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10127236. Licensed CC0.

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