# Sleep and Cardiovascular Health in Adolescence

> **NIH NIH R01** · SRI INTERNATIONAL · 2020 · $756,559

## Abstract

PROJECT SUMMARY/ABSTRACT
 Insomnia is highly prevalent in adolescence, particularly in post-pubertal girls and tends to persist over time.
Insomnia is considered a hyperarousal disorder, in which abnormally elevated levels of cognitive and
physiological activation, particularly evident at bed-time, prevent individuals from falling asleep and having a
restorative night’s sleep. Hyperarousal is a major pathophysiological mechanism linking insomnia with poor
mental and physical health, including cardiovascular (CV) disease. We and others have shown evidence of
autonomic nervous system (ANS) dysfunction such as hyperactivation of the sympathetic branch of the ANS –
a major etiological factor in CV disease – in young and midlife adults, both before and during sleep. It is
unknown if ANS hyperarousal is evident in adolescents with insomnia.
 The biological basis for an emerging sex difference in insomnia prevalence in adolescence is unknown. Our
pilot data reveal intriguing evidence of sex-differences in basic and stress-dependent ANS modulation during
sleep in adolescents with girls showing a greater ANS response to stress. These data suggest the existence of
a predisposing and stress-dependent ANS vulnerability in female adolescents, a potential pathway to develop
insomnia. This proposal takes a novel approach to investigating the manifestation of physiological ANS and CV
hyperarousal in adolescents with insomnia by experimentally manipulating the pre-sleep arousal state via
stress-induced ANS up-regulation and relaxation-driven ANS down-regulation. In addition, the proposal
focuses on sex differences in ANS and CV responses to pre-sleep ANS manipulation, potentially addressing
the question of why female sex is a major risk factor for insomnia.
 We aim to test 110 male and female high-school students (16-18y) with and without DSM-5 Insomnia
Disorder, during a regular in-lab polysomnographic night (baseline) and under experimental pre-sleep stress
(psychosocial stressor) and pre-sleep relaxation (Virtual reality ANS bio-feedback) intervention nights, using
state-of-the-art, noninvasive, beat-to-beat ANS and CV measures, including blood pressure, to assess
nocturnal ANS and CV function in adolescents with insomnia (Aim 1); the impact of pre-sleep ANS arousal
levels on nocturnal ANS and CV function, and sleep in adolescents with and without insomnia, considering
possible sex differences (Aim 2), and the extent to which nocturnal ANS and CV function mediate the effect of
pre-sleep arousal levels on objective and perceived sleep quality (Aim 3).
 This proposal has the potential to elucidate pathophysiological ANS hyperarousal underlying Insomnia
Disorder in adolescence, including potential reasons for the vulnerability to insomnia in girls, leading to better
recognition and potentially new treatment strategies of this disorder targeted at the state of ANS hyperarousal
in the pre-sleep period.

## Key facts

- **NIH application ID:** 9839663
- **Project number:** 5R01HL139652-03
- **Recipient organization:** SRI INTERNATIONAL
- **Principal Investigator:** Massimiliano de Zambotti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $756,559
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839663

## Citation

> US National Institutes of Health, RePORTER application 9839663, Sleep and Cardiovascular Health in Adolescence (5R01HL139652-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9839663. Licensed CC0.

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