# Tracking the dynamic trajectory of behavioral, physiological, and neurobiological stress responses in female adolescents at high and low familial risk for depression.

> **NIH MH R01** · MCLEAN HOSPITAL · 2026 · $705,959

## Abstract

Project Summary/Abstract. Stress and a parental history of Major Depressive Disorder (MDD) are among the
most potent risk factors for future MDD development. Evidence suggests that the offspring of parents with
MDD are especially vulnerable to the development of maladaptive responses to stress. Early adolescence is a
critical window for studying MDD risk, as this developmental stage is just prior to the peak period of initial MDD
onsets and a time of enhanced stress sensitivity, especially among females. Despite the importance of stress
in MDD onset, the neural mechanisms underlying stress responses in female adolescents at high familial risk
for MDD remain unclear. Furthermore, little is known about how stress-induced brain network changes may be
linked to physiological and behavioral responses to stress and be predictive of future MDD onset. In this R01
resubmission, we aim to test a model in which having a parental history of MDD increases the risk for
dysfunctional dynamic default mode network (DMN) – Central Executive Network (CEN) stress responses, two
networks consistently linked to MDD pathophysiology and stress responsivity, prior to the onset of depression.
Specifically, we expect that adolescents with versus without a parental MDD history will spend more time and
persist longer in a DMN-CEN co-activated pattern in response to stress. We further hypothesize that this
maladaptive DMN-CEN pattern will predict maladaptive psychophysiological and behavioral responses seen in
the adolescents’ natural environment. Together, we expect that this stress sensitive profile of dysfunctional
dynamic DMN-CEN, psychophysiological, and behavioral responses will predict future depression onset. We
focus on DMN-CEN dynamics given accumulating evidence showing that, relative to static network properties,
brain network dynamic properties may be more robustly associated with MDD pathophysiology as well as the
behavioral and psychophysiological processes impacted by stress and 

## Key facts

- **NIH application ID:** 11319792
- **Project number:** 5R01MH137441-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Emily  Belleau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** MH
- **Fiscal year:** 2026
- **Award amount:** $705,959
- **Award type:** 5
- **Project period:** 2025-04-15T00:00:00 → 2030-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11319792

## Citation

> US National Institutes of Health, RePORTER application 11319792, Tracking the dynamic trajectory of behavioral, physiological, and neurobiological stress responses in female adolescents at high and low familial risk for depression. (5R01MH137441-02). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11319792. Licensed CC0.

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