# Physiological and Behavioral Basis of Circadian Rhythm Delayed Sleep-Wake Phase Disorder

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $655,655

## Abstract

PROJECT SUMMARY/ABSTRACT
Delayed Sleep Wake Phase Disorder (DSWPD) is a common circadian rhythm sleep-wake disorder that is
characterized by difficulty in initiating sleep at night and subsequent difficulty in waking at times required for work
or school. Consequently, DSWPD is often associated with excessive daytime sleepiness, reduced academic and
work performance, mood disturbances and reduced quality of life. Considering the significant negative impact of
DSWPD on sleep quality, performance, mental and physical health and well-being, the physiological basis of the
disorder surprisingly remains unclear. Classically, DSWPD is assumed to stem from a delay of central circadian
timing. However, recent evidence shows that those clinically diagnosed with DSWPD fall into at least two distinct
phenotypes: those with delayed circadian timing and sleep (DSWPD1) and those with typical circadian timing
but delayed sleep (DSWPD2). Using pupillometry, our group has shown differences in light sensitivity between
the DSWPD1 and DSWPD2 subtypes, as well as within the DSWPD1 group (high (HLS) and low sensitivity to
light (LLS)), indicating that clinically diagnosed DSWPD likely represents a complex interplay between underlying
physiological differences and behaviors that can affect sleep timing. However, current diagnostic criteria do not
consider these distinct phenotypes, which can limit diagnostic accuracy and hinder the development of
personalized treatments that target the underlying alterations in physiology and behavior of these DSWPD
subtypes. The overall goal of the proposed research is to identify the physiological basis of DSWPD subtypes,
and to use these findings to inform development of mechanistically based approaches in circadian medicine.
This project will enroll 220 patients with DSWPD who will undergo circadian physiological and behavioral
phenotyping by actigraphy, dim light melatonin sampling, pupillary light sensitivity, as well as assessment of
mood, alertness and meal timing using questionnaires. In addition, we will evaluate light sensitivity in LLS
DSWPD1, as measured by the suppression of melatonin, and test whether the SSRI citalopram can enhance
light sensitivity. Finally, mathematical modeling will be used to integrate physiological (pupillometry) and
behavioral assessments to identify DSWPD subtypes. The proposed research will form the basis for the
development of light sensitivity-based tools and algorithms that integrate physiological and behavioral
biomarkers which can lead to a personalized multimodal approach for the care of patients with circadian rhythm
disorders.

## Key facts

- **NIH application ID:** 10937779
- **Project number:** 1R01HL174661-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Sabra M Abbott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $655,655
- **Award type:** 1
- **Project period:** 2024-09-17 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937779

## Citation

> US National Institutes of Health, RePORTER application 10937779, Physiological and Behavioral Basis of Circadian Rhythm Delayed Sleep-Wake Phase Disorder (1R01HL174661-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10937779. Licensed CC0.

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