Circadian and Ultradian Cortisol Rhythms in Chronic Sleep Continuity Disturbance

NIH RePORTER · NIH · K23 · $153,760 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Approximately 30-50% of the US population experiences acute sleep continuity disturbance (i.e., insomnia) per annum, and approximately 10% of the population report chronic levels of insomnia. Chronic insomnia (CI) is associated with significant daytime impairment and is a substantial risk factor for multiple psychiatric and medical disorders. Given CI's prevalence and consequences, it is essential to identify factors that perpetuate this disorder. One of the leading candidates for the neurobiological basis of CI is hypothalamic-pituitary-adrenal (HPA) axis dysregulation, specifically, alterations in cortisolinergic tone. Cortisol secretory patterns exhibit both a circadian and an ultradian rhythm. Ultradian pulses (i.e., every 60-120 minutes) are hypothesized to be involved in the maintenance of wakefulness during the day and may be related to the inhibition of wakefulness at night (i.e., the inhibition of pulses promotes the consolidation of sleep). While cortisol pulses naturally occur with transient awakenings, we hypothesize that these pulses can become a conditioned phenomenon in CI that predisposes the individual to awaken and/or experience prolonged nocturnal awakenings. Increased cortisol pulses during the day may also be expected because of the increased effort required to maintain wakefulness, and in turn, these increased pulses may further condition the aberrant occurrence of cortisol pulses at night. The scientific aims are (1) to evaluate whether subjects with CI, as compared to good sleepers, exhibit greater ultradian cortisol pulsatility during the day and/or at night, and (2) to quantify the association between ultradian cortisol secretion and metrics related to spontaneous awakenings from sleep (i.e., timing, frequency, duration, and EEG spectral profile of the awakenings). The proposed study will be conducted as a between-subjects design, examining 20 individuals with CI and 20 good sleepers during two consecutive nights in the laboratory (Night 1 is a screening night). While in the lab, blood will be sampled every 10 minutes for 24 hours and sleep will be polysomographically recorded. A refined delineation of both the circadian and ultradian aspects of cortisol secretion may allow for a better understanding of the etiology of chronic insomnia, the efficacy of established treatments, and potentially the development of new therapeutic approaches. The training plan includes educational activities that encompass three broad topic areas: (1) general skills (i.e., professional, ethics, and research training activities), (2) principles and practice and methodology issues related to neuroendocrinology, and (3) principles and practice and methodology issues related to behavioral sleep medicine and sleep medicine. The training plan builds upon the applicant's background in depression-related sleep research and stress physiology and provides the necessary training in neuroendocrinology, behavioral sleep medicine, and sleep medici...

Key facts

NIH application ID
10137997
Project number
5K23HL141581-03
Recipient
UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
Principal Investigator
Ivan Vargas
Activity code
K23
Funding institute
NIH
Fiscal year
2021
Award amount
$153,760
Award type
5
Project period
2019-10-01 → 2024-05-31