# Functional and Neurochemical Substrates of Amygdala-Frontal Circuitry across Development and Anxiety

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $13,717

## Abstract

Generalized anxiety disorder (GAD) is a debilitating illness characterized by persistent and exaggerated
worrying. It can disruptively interfere with everyday functioning, and is associated with poor health, and
negative financial and social outcomes. As one of the most common anxiety disorders, GAD affects millions of
Americans each year with a 12-month prevalence of 3.1%. Compared to the stable rates in children and
younger adolescents, new onset of GAD increases substantially from 16 to 26 years of age, suggesting the
transition from late adolescence to early adulthood as a key high-risk stage for GAD. Amygdala-frontal
circuitry, particularly functional interactions between the amygdala and anterior cingulate cortex (ACC), plays a
critical role in threat processing and emotional regulation, and has been centrally implicated in anxiety
disorders. Specifically, adult-like connectivity/activity in the ACC appears to emerge in late adolescence, and
gradually develops into adulthood as an effective top-down inhibitory regulation. It is possible that
developmental deviations of the amygdala-ACC interaction may trigger the development of GAD during the
transition from late adolescence to early adulthood. Therefore, a cross-sectional multimodal study (fMRI+MRS
[functional MRI + magnetic resonance spectroscopy]) is designed to examine the developmental trajectories of
amygdala-ACC circuitry in healthy (N = 40) and anxious (N = 40) participants between 16 to 26 years old. The
overarching objective of this study is to uncover an integrated functional-neurochemical biomarker for healthy
versus anxious development. Specifically, fMRI will be used to measure the functional connectivity between
the amygdala and the ACC in response to social threats; 1H-MRS will be used to measure the concentrations
of the primary excitatory neurotransmitter glutamate and the primary inhibitory neurotransmitter GABA (γ-
aminobutyric acid) in the ACC. Disrupted functional connectivity and imbalanced neurochemistry as identified
in this study can serve as objective and developmentally sensitive markers for identifying at-risk individuals for
early intervention and prevention of GAD. The integrated functional-neurochemical biomarker of healthy and
anxious development can also guide the development of novel treatments targeting at the glutamatergic and
GABAergic systems from a neurodevelopmental perspective.

## Key facts

- **NIH application ID:** 10058131
- **Project number:** 1R21MH116475-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Shaolin Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $13,717
- **Award type:** 1
- **Project period:** 2020-08-12 → 2020-11-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058131

## Citation

> US National Institutes of Health, RePORTER application 10058131, Functional and Neurochemical Substrates of Amygdala-Frontal Circuitry across Development and Anxiety (1R21MH116475-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10058131. Licensed CC0.

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