Related Experiment Video
Updated: May 10, 2025
08:36
Collecting Sleep, Circadian, Fatigue, and Performance Data in Complex Operational Environments
Published on: August 8, 2019
11.8K
Indirect Effect Model with Surge Function for Describing Melatonin Circadian Rhythm: Quantitative Comparison and
Zhanhui Lv1,2, Zimo Zhang3, Lu Wang2
1Department of Clinical Pharmacology, Pharmacy College, Nanjing Medical University, Nanjing, China.
Neuroendocrinology
|April 27, 2025
Summary
Delayed sleep-wake phase disorder (DSWPD) patients show altered melatonin production and delayed dim light melatonin onset (DLMO) compared to normal sleepers. Quantitative pharmacology models reveal key differences in circadian melatonin profiles.
Area of Science:
- Pharmacology
- Chronobiology
- Sleep Medicine
Background:
- Investigating circadian rhythm of melatonin in normal sleepers and DSWPD patients.
- Utilizing quantitative pharmacology to understand sleep disorders and their mechanisms.
Purpose of the Study:
- To quantitatively compare melatonin circadian rhythm characteristics between normal sleepers and DSWPD patients.
- To predict melatonin concentration and DLMO using Bayesian estimation.
Main Methods:
- Developed an indirect effect model with a surge function.
- Employed diagnostic plots, VPC, and bootstrapping for model evaluation.
- Used Monte Carlo simulations and Bayesian estimation for quantitative comparisons and predictions.
Main Results:
- DSWPD patients exhibit a ~7-hour delay in DLMO and reduced melatonin production rate constants.
- Melatonin elimination rate constants were similar between DSWPD patients and normal sleepers.
- Bayesian estimation accurately predicted melatonin levels and DLMO in DSWPD patients within ±10% error.
Conclusions:
- DSWPD patients have altered circadian melatonin profiles, including reduced production and delayed DLMO.
- The developed model effectively estimates melatonin rhythm characteristics and DLMO using sparse data.
- Quantitative pharmacology provides insights into DSWPD pathophysiology.
Related Concept Videos
01:19Management of Insomnia
185
The sleep cycle, an integral part of human health, consists of several stages with distinct characteristics and functions. It begins with a transition from wakefulness to sleep, known as the light sleep phase, followed by the restorative deep sleep phase, essential for physical recovery and growth. The cycle concludes with the Rapid Eye Movement (REM) phase, characterized by high brain activity and vivid dreaming. Insomnia, a prevalent sleep disorder, involves difficulty falling asleep, staying...
185
02:19Circadian Rhythms and Gene Regulation
4.0K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.0K
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
97
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
97
01:11Understanding Sleep
198
Sleep, an essential biological state, involves significant reductions in physical activity, sensory awareness, and interaction with the environment. This complex physiological process is primarily regulated by specific brain regions, notably the hypothalamus and pons, which govern the sleep-wake cycle or circadian rhythm.
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...
198
01:24Sleep-Wake Cycles
1.1K
Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
1.1K
01:13Insufficient Sleep and Sleep Deprivation
118
Insufficient sleep refers to not getting the recommended amount of sleep for optimal functioning, even if it's just slightly less than needed. Sleep insufficiency may occur due to lifestyle choices, such as staying up late for social events or work, resulting in routinely getting less sleep than required. For example, consistently sleeping 6 hours when the body needs 7-9 hours can lead to cumulative effects on health and well-being.
Sleep deprivation is a more severe form of sleep loss...
Sleep deprivation is a more severe form of sleep loss...
118