# Combining human and nonhuman primate studies to understand the pathophysiology of childhood anxiety disorders

> **NIH NIH U01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $376,343

## Abstract

Project Summary
Anxiety disorders (ADs) are the most prevalent psychiatric ailments in children and adolescents. Childhood
ADs substantially impair development and confer high risk for later psychopathology including persistent
anxiety, depression and comorbid substance abuse. Given the high prevalence and long-term negative impact
of childhood ADs, it is critical to successfully treat ADs early in development. Unfortunately, many children with
these disorders either fail to fully respond to treatment or relapse. Understanding the biology of childhood ADs
is crucial for developing early interventions with the potential to reduce the chronicity and comorbidity
associated childhood onset. Cross-species conservation of brain-behavior relationships provides a unique
opportunity to link basic neuroscience in nonhuman primates with clinical neuroscience in childhood ADs to
identify the neural substrates of childhood anxiety. The proposed project will capitalize on this exceptional
advantage by using two integrated approaches: 1) a multisite multimodal imaging study that extends promising
basic science findings in nonhuman primates to a large sample of preadolescents with ADs and 2) a molecular
study that translates neural findings in childhood ADs to gene expression studies in nonhuman primates using
our fully-phenotyped nonhuman primate brain bank focused on alterations in neuroplasticity transcripts.
Findings from our nonhuman primate studies highlight the importance of identifying neural substrates that
contribute to shared variance across ADs, as well as specific neural substrates that are associated with
particular anxiety phenotypes. This approach is consistent with evidence of shared and specific features of
childhood ADs: most children with ADs present with an admixture of symptoms and treatment responses are
similar across diagnoses suggesting shared neural substrates; however, substantial variation in symptoms and
presentation suggest heterogeneous neural substrates. The study will focus on three specific aims: (1) Identify
neural alterations that are shared among childhood generalized anxiety disorder, social anxiety disorder, and
separation anxiety disorder; (2) determine neural alterations linked to specific anxiety-relevant RDoC
constructs (i.e. acute, potential, and sustained threat, and generalization of conditioned fear); and (3)
Investigate molecular alterations in brain regions central to childhood ADs, guided by the childhood AD studies
in Aims 1 and 2, with a particular focus on neuroplasticity-related alterations. Studying a large sample of AD
children is critical to parse the heterogeneity common in childhood ADs; to achieve this goal, we have
assembled three sites with expertise in anxiety (nonhuman primate models of anxiety, childhood anxiety,
developmental psychology) and advanced methods (gene expression, neuroimaging, and statistics). Ultimately
we aim to elucidate the neurobiological mechanisms underlying childhood ADs to i...

## Key facts

- **NIH application ID:** 10414803
- **Project number:** 5U01MH112913-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jennifer Urbano Blackford
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $376,343
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414803

## Citation

> US National Institutes of Health, RePORTER application 10414803, Combining human and nonhuman primate studies to understand the pathophysiology of childhood anxiety disorders (5U01MH112913-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10414803. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*