Interindividual variability in sensitivity to light synchronisation effects and circadian characterization of individuals

The human circadian system represents an evolutionary adaptation to the rhythmic changes of the external environment driven by the Earth’s rotation, resulting in a near-24-hour endogenous cycle.

The human circadian system is synchronized to the external light–dark cycle, with light serving as the primary zeitgeber regulating physiological and behavioral rhythms, including melatonin secretion. However, accumulating evidence indicates substantial interindividual variability in circadian sensitivity to light, which may critically influence the effectiveness of light-based interventions. Nocturnal light exposure induces highly variable melatonin suppression across individuals, suggesting marked differences in circadian photoreception.

Light information is conveyed via intrinsically photosensitive retinal ganglion cells, and their melanopsin-mediated responses can be assessed non-invasively using pupillometry, particularly the post-illumination pupil response. In addition to physiological variability, genetic polymorphisms in circadian clock genes (e.g., PER2, PER3) and phototransduction pathways (e.g., OPN4) have been associated with differences in sleep timing, chronotype, and light responsiveness. Together, these findings highlight the need for a multimodal approach to characterize individual differences in circadian light sensitivity.

This study investigates behavioral, physiological, and genetic determinants of circadian light sensitivity using a comprehensive multimodal design. Participants undergo structured assessment including a novel questionnaire targeting sensitivity to morning, evening, and nocturnal light (QASTL), alongside standardized instruments assessing chronotype (MEQ), sleep quality (PSQI), and depressive symptoms (Beck Depression Inventory). Physiological measures include salivary melatonin profiling assessed by radioimmunoassay and pupillometry to capture melanopsin-driven pupil responses. Genotyping is performed for selected polymorphisms associated with circadian regulation and light perception (PER2, PER3, OPN4).

Melatonin suppression is assessed under controlled conditions using monochromatic blue light exposure (λ = 480 nm, 1000 lux) delivered via standardized light therapy glasses. Participants undergo daytime saliva sampling to establish baseline melatonin profiles, followed by nocturnal light exposure during which the degree of melatonin suppression and subsequent recovery to physiological levels are quantified as markers of circadian responsiveness.

The current analysis is based on data from 163 volunteers (mean age 20.3 ± 7.2 years; 76 males, 87 females). A subset of participants (n = 45), stratified across chronotypes, undergoes detailed laboratory assessment. Preliminary observations indicate substantial interindividual variability in melatonin suppression responses, supporting the presence of distinct sensitivity phenotypes. Ongoing analyses aim to determine the extent to which pupillary responses, questionnaire-derived measures, and genetic polymorphisms predict physiological sensitivity to light.

The aim of this study is to identify individuals with high and low sensitivity to light and to characterize circadian system function in those exhibiting reduced responsiveness to light therapy. By integrating behavioral, physiological, and genetic markers, this work seeks to improve prediction of therapeutic outcomes and contribute to the development of personalized chronotherapeutic strategies. A better understanding of interindividual variability in circadian photoreception may also help refine the timing, intensity, and spectral composition of light exposure in both clinical and real-world settings. Ultimately, such stratification could reduce non-response rates and improve the efficiency of interventions targeting circadian misalignment and related disorders.

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