Multimodal circadian phenotyping reveals distinct mechanisms of photic entrainment failure in two sighted patients with non-24-hour sleep-wake disorder
Abstract
Non-24-h sleep-wake disorder (N24SWD) is a rare circadian rhythm disorder in sighted patients whose underlying pathophysiology remains poorly understood. Here, we aimed to investigate the mechanisms of impaired circadian entrainment by combining assessments of retinal and melanopsin function, circadian light responsiveness and endogenous circadian rhythmicity. Two sighted patients with confirmed N24SWD underwent comprehensive circadian phenotyping targeting three complementary components of the circadian system: retinal and melanopsin-mediated photoreception, endogenous circadian timing, and circadian responsiveness to light. Retinal function was assessed using full-field electroretinography and chromatic pupillometry with measurement of the post-illumination pupil response (PIPR). Endogenous circadian phase and period were characterized through continuous core body temperature monitoring and hourly plasma melatonin and cortisol sampling during a 25-h multiple-nap protocol conducted under modified constant-routine conditions. Circadian light responsiveness was evaluated using three 15-min light exposures delivered at different irradiance levels and circadian phases across three consecutive nights, with simultaneous assessment of light-induced melatonin suppression. The first subject exhibited preserved melanopsinergic response as indicated by a normal PIPR, but showed no melatonin suppression regardless of light timing or illuminance levels. The intrinsic circadian period of…
Read the paper
Related studies
- A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Evaluating the Evidence Base of Melatonin, Light Exposure, Exercise, and Complementary and Alternative Medicine for Patients with Insomnia Disorder
- Use of Melatonin and/on Ramelteon for the Treatment of Insomnia in Older Adults: A Systematic Review and Meta-Analysis
- Influence of evening light exposure on polysomnographically assessed night-time sleep: A systematic review with meta-analysis
- Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation
- Significant potential of melatonin therapy in Parkinson’s disease – a meta-analysis of randomized controlled trials
- Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.