# A translational approach for identifying factors and mechanisms underlying pathological anxiety in preadolescent girls

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $777,346

## Abstract

Project Summary/Abstract
Persistent and symptomatic anxiety during childhood is pathological and is a risk factor for the later development
of stress-related psychopathology. Anxious young girls are particularly at risk, as during the transition to
adolescence the prevalence of anxiety disorders (ADs) and depression markedly increases in females compared
to males. Our work in children demonstrates that persistent and symptomatic anxiety is dimensionally related to
altered function of neural circuits identified to be associated with responses to threat. Additionally, anxiety
symptoms and levels of distress are highly overlapping between children that do and do not meet DSM-5 criteria
for ADs. These findings, along with the risk conferred by early-life anxiety, provide a rationale for studying the
broad range of pathological anxiety in preadolescent girls. In addition to daytime worries and fears, sleep-related
symptoms (e.g. pre-sleep arousal, poor sleep quality) are common in anxiety, occurring in up to 90% of youth
with ADs. It is critical to understand how sleep physiology relates to the pathophysiology of childhood anxiety
because sleep is a homeostatic regulator that is involved in learning and memory consolidation, and also
influences emotion regulation. Here, we will use a translational approach leveraging our nonhuman primate
(NHP) model of pathological anxiety to conduct parallel neuroimaging and EEG sleep studies in preadolescent
girls and preadolescent female rhesus monkeys with pathological anxiety. Using multimodal imaging, hdEEG
sleep recordings, and home sleep EEG data, studies in preadolescent girls with pathological anxiety will explore
hypotheses implicating the basolateral amygdala (BLA) and anterior insula (AI) in mediating altered anxiety-
related daytime neural circuit function as well as alterations in REM and regional slow wave sleep. Studies using
similar methods will be performed in NHPs that will be aimed at causal mechanisms. By chemogenetically
activating BLA or AI neurons prior to sleep, the NHP studies will test the roles of the BLA and AI in mediating the
linkage between alterations in sleep and daytime neural circuit function that are associated with pathological
anxiety. Understanding daytime neural alterations associated with pathological anxiety in relation to disrupted
sleep physiology is highly relevant for elucidating mechanisms underlying childhood pathological anxiety and in
conceptualizing new treatment approaches.

## Key facts

- **NIH application ID:** 10873049
- **Project number:** 5R01MH132671-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Ned H Kalin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $777,346
- **Award type:** 5
- **Project period:** 2023-06-21 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873049

## Citation

> US National Institutes of Health, RePORTER application 10873049, A translational approach for identifying factors and mechanisms underlying pathological anxiety in preadolescent girls (5R01MH132671-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873049. Licensed CC0.

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