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Circadian and Ultradian Cortisol Rhythms in Chronic Sleep Continuity

Award Number: K23HL141581
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 10/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Circadian and Ultradian Cortisol Rhythms in Chronic Sleep Continuity - 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 medicine to further explore and document any association of HPA-axis abnormalities with persistent wakefulness at night. The pedagogic approach includes routine one-on-one mentorship, directed readings, course work, mini-fellowships, lab-based trainings, and conferences/workshops.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	National Center on Sleep Disorders Research	002	6	7/31/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	National Center on Sleep Disorders Research	001	6	5/16/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$118,777
2025	2023	UNIVERSITY OF ARKANSAS	1125 W MAPLE ST STE 316	FAYETTEVILLE	AR	72701	WASHINGTON	USA	National Center on Sleep Disorders Research	000	5	5/15/2025	NON-COMPETING CONTINUATION	-$118,777
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $153,760 )
2023	2023	UNIVERSITY OF ARKANSAS SYSTEM	1125 WEST MAPLE STE 210	FAYETTEVILLE	AR	72701	WASHINGTON	USA	National Center on Sleep Disorders Research	000	5	5/10/2023	NON-COMPETING CONTINUATION	$153,760
														Subtotal = $153,760

Issue Date FY: 2022 ( Subtotal = $153,760 )
2022	2022	UNIVERSITY OF ARKANSAS SYSTEM	1125 WEST MAPLE STE 210	FAYETTEVILLE	AR	72701	WASHINGTON	USA	National Center on Sleep Disorders Research	000	4	5/22/2022	NON-COMPETING CONTINUATION	$153,760
														Subtotal = $153,760

Issue Date FY: 2021 ( Subtotal = $153,760 )
2021	2021	UNIVERSITY OF ARKANSAS SYSTEM	1125 WEST MAPLE STE 210	FAYETTEVILLE	AR	72701	WASHINGTON	USA	National Center on Sleep Disorders Research	002	3	5/20/2021	NON-COMPETING CONTINUATION	$153,760
2021	2020	UNIVERSITY OF ARKANSAS SYSTEM	1125 WEST MAPLE STE 210	FAYETTEVILLE	AR	72701	WASHINGTON	USA	National Center on Sleep Disorders Research	001	2	2/1/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$175,432
2021	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	National Center on Sleep Disorders Research	000	1	2/1/2021	NEW	-$175,432
														Subtotal = $153,760

Issue Date FY: 2020 ( Subtotal = $153,760 )
2020	2020	UNIVERSITY OF ARKANSAS SYSTEM	1125 WEST MAPLE STE 210	FAYETTEVILLE	AR	72701	WASHINGTON	USA	National Center on Sleep Disorders Research	001	2	4/3/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$153,760
2020	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	National Center on Sleep Disorders Research	000	1	3/31/2020	NEW	$0
														Subtotal = $153,760

Issue Date FY: 2019 ( Subtotal = $180,846 )
2019	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	National Center on Sleep Disorders Research	001	1	9/16/2019	NEW	$0
2019	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	National Center on Sleep Disorders Research	000	1	6/14/2019	NEW	$180,846
														Subtotal = $180,846

Grand Total All Awards = $795,886

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Circadian and Ultradian Cortisol Rhythms in Chronic Sleep Continuity

Award Number: K23HL141581

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 10/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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