# Effects of Early Life Stress and Sleep Disturbance on Frontolimbic Development and Risk for Depression Across Adolescence

> **NIH NIH F32** · STANFORD UNIVERSITY · 2024 · $81,892

## Abstract

Project Summary/Abstract
Major depressive disorder (MDD) is among the most prevalent, recurrent, and functionally debilitating of all
psychiatric disorders. The incidence of MDD rises sharply during adolescence, and individuals who have an
onset of MDD in adolescence tend to have a more chronic and severe course of depression than do those with
a later onset. Thus, there is an urgent need to develop effective approaches for early identification, prevention,
and intervention for MDD. Experiences of early life adversity (ELA), which affect over 40% of children, are a
strong predictor of MDD. Research suggests that one pathway by which ELA increases risk for MDD is through
alterations in the structural and functional development of frontolimbic regions implicated in stress reactivity
and regulation; however, the direction of these effects and how they unfold over time are not known. Moreover,
the biobehavioral mechanisms by which ELA influences neurodevelopment and risk for MDD are not well
understood. In this context, sleep disturbances is a significant risk factor for MDD across the lifespan and is an
underexplored pathway by which ELA might increase risk for MDD during adolescence. Sleep disturbances
tend to increase during adolescence due to a combination of normative biological and psychosocial changes;
indeed, over 70% of high-school students report getting insufficient sleep. Emerging research suggests that
adolescents with greater sleep disturbances have both attenuated white matter development in tracts that
connect frontolimbic regions and heightened frontolimbic reactivity to stress. The overlapping neurobiological
and health effects of ELA and sleep disturbances suggest that sleep disturbance is a critical pathway that links
ELA to frontolimbic alterations and increased risk for MDD. The proposed research addresses critical gaps in
the literature by examining the multivariate and longitudinal effects of ELA, sleep disturbances, and frontolimbic
connectivity during adolescence and how these factors predict risk for depression in young adulthood.
Leveraging data from a multimethod longitudinal study, the proposed project investigates sleep disturbances
as a pathway linking ELA with alterations in frontolimbic development and risk for MDD across adolescence
and young adulthood (9-20 years of age). The results of this project will not only increase our understanding of
the neurobiological mechanisms by which ELA relates to increased risk for MDD, but will also provide insight
into sleep disturbances as a potential target of intervention during adolescence to ameliorate the effects of
ELA. Moreover, the proposed training plan will enable the applicant to gain theoretical and methodological
expertise in studying the relations among ELA, sleep quality, frontolimbic development, and psychopathology
during adolescence, and to develop professional skills necessary to transition to an independent research
career. Stanford University, the institutio...

## Key facts

- **NIH application ID:** 10936530
- **Project number:** 5F32MH135657-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jessica Phuong Uy
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $81,892
- **Award type:** 5
- **Project period:** 2023-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936530

## Citation

> US National Institutes of Health, RePORTER application 10936530, Effects of Early Life Stress and Sleep Disturbance on Frontolimbic Development and Risk for Depression Across Adolescence (5F32MH135657-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10936530. Licensed CC0.

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