# Neonatal Brain Activity and Risk for Anxiety Disorders in Early Childhood

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $377,554

## Abstract

Anxiety disorders are the most common form of pediatric psychiatric illness, affecting up to 30% and severely
impairing up to 20% of all youth prior to age 18. Unfortunately, up to 50% of children remain symptomatic even
with the best available treatment, making anxiety disorders a major public health problem. A major barrier to
devising new treatments for anxiety disorders is that the brain pathophysiology likely starts at birth or earlier,
but little is known about the earliest stages of abnormal brain development. This proposal measures brain
activity and brain connectivity in neonates at high versus low risk for developing an anxiety disorder; uncovers
the first steps in the neurodevelopmental pathway that results in an anxiety disorder; and provides a framework
for early identification, prevention, and new treatment development. Anxiety disorders in adults are associated
with increased activity in brain networks that respond to changes in the environment or `novelty', coupled with
decreased activity in brain networks that regulate this novelty response. Behavioral and EEG data suggest that
these processes may start in infancy. Infants with an enduring enhanced behavioral and neural (as measured
by EEG) reaction to novelty are described as having the `behavioral inhibition (BI)' temperament and are at
high risk for later development of an anxiety disorder. High maternal prenatal anxiety is similarly associated
with both increased reactivity to novelty and increased risk for developing an anxiety disorder in offspring. The
objective of this application is to identify the specific brain networks in newborn infants that are associated with
this enduring enhanced response to novelty and that represent increased risk for later development of an
anxiety disorder. To achieve this objective, we will use task-based fMRI to measure regional brain activity that
is elicited by sudden, unexpected auditory stimuli (`oddballs') in sleeping neonates. Activity evoked by the initial
oddballs represents the initial novelty response, while activity evoked by later oddballs represents the potential
regulatory response. The central hypotheses are that neonates at high risk for developing an anxiety disorder
(on the basis of either high maternal anxiety or high BI) demonstrate increased activity in brain networks that
respond to novelty; coupled with decreased activity in regulatory networks after repeated presentation of the
stimuli. We will also use resting-state fMRI to measure network connectivity, and we predict that risk for anxiety
disorders will be associated with altered connectivity in networks that respond to novelty. We will test these
hypotheses by recruiting pregnant mothers and obtaining MRI in offspring (n=150) within 2 weeks of birth. We
will then assess the neonates and mothers at 3 additional visits over the first 2 years of life. We will assess
maternal anxiety during pregnancy with questionnaires and infant temperament in the first 2 years with...

## Key facts

- **NIH application ID:** 10789865
- **Project number:** 5R01MH122389-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Chad Michael Sylvester
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $377,554
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10789865

## Citation

> US National Institutes of Health, RePORTER application 10789865, Neonatal Brain Activity and Risk for Anxiety Disorders in Early Childhood (5R01MH122389-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10789865. Licensed CC0.

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