Functional decoupling of melatonin suppression and circadian phase resetting in humans
Open accessAbstract
Key points: There is assumed to be a monotonic association between melatonin suppression and circadian phase resetting induced by light exposure. We tested the association between melatonin suppression and phase resetting in humans. Sixteen young healthy participants received nocturnal bright light (∼9500 lux) exposure of continuous or intermittent patterns, and different durations ranging from 12 min to 6.5 h. Intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every bright light stimulus in an intermittent exposure pattern induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest that phase shifts and melatonin suppression are functionally independent such that one cannot be used as a proxy measure of the other. Continuous experimental light exposures show that, in general, the conditions that produce greater melatonin suppression also produce greater phase shift, leading to the assumption that one can be used as a proxy for the other. We tested this association in 16 healthy individuals who participated in a 9‐day inpatient protocol by assessing melatonin suppression and phase resetting in response to a nocturnal light exposure (LE) of different patterns: (i) dim‐light control (<3 lux; n = 6) or (ii) two 12‐min intermittent bright light pulses (IBL) separated by 36 min of darkness (∼9500 lux; n = 10). We compared these results with historical data from additional LE patterns: (i) dim‐light control (<3 lux; n = 11); (ii) single continuous bright light exposure of 12 min ( n = 9), 1.0 h ( n = 10) or 6.5 h ( n = 6); or (iii) an IBL light pattern consisting of six 15‐min pulses with 1.0 h dim‐light recovery intervals between them during a total of 6.5 h ( n = 7). All light exposure groups had significantly greater phase‐delay shifts than the dim‐light control condition ( P < 0.0001). While a monotonic association between melatonin suppression and circadian phase shift was observed, intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every IBL stimulus induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest unique specificities in how light‐induced phase shifts and melatonin suppression are mediated such that one cannot be used as a proxy measure of the other.
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Melatonin suppression and circadian phase shifts are not arising from a unitary pathway resulting in a direct relationship between them.
“However, these two effects are not arising from a unitary pathway resulting in a direct relationship between melatonin suppression and phase shifts. There is now accruing evidence that they may be indeed separable [63].”
From Effects of light on human circadian rhythms, sleep and mood (2019) · cites this paper as [63]
The Results section reports no significant association between melatonin suppression and phase shifts within any of the six light-exposure conditions. The Discussion concludes that the responses are not closely functionally coupled, supporting the claim that suppression does not directly predict phase shifts. It proposes, but does not establish, a pathway-based explanation; the categorical claim that they do not arise from a unitary pathway goes beyond the evidence. (LLM, conf=0.85)
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- Authors
- Rahman, S. A., St Hilaire, M. A., Gronfier, C., Chang, A., Santhi, N., Czeisler, C. A., Klerman, E. B., & Lockley, S. W.
- Affiliations
- Brigham and Women's Hospital (US)
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham & Women's Hospital Boston MA USA
- Lyon 1 Université (FR)
- Corresponding author
- Rahman, Shadab A.
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2018-04-29
- Volume
- 596
- Issue
- 11
- Pages
- 2147-2157
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC5983136
- OpenAlex
- W2806949397
- Cited by
- 58
- References
- 38
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 2 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 12 · 2018: 4
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- National Space Biomedical Research Institute (HFP02801, HFP02802)
- Harvard Catalyst
- National Institutes of Health (HL094654, P01‐AG09975, R01‐HL114088, RC2‐HL101340‐0, K02‐HD045459, K24‐HL105664, T32‐HL07901, 1UL1 TR001102‐01, 8UL1TR000170‐05, UL1 RR 025758)
- National Aeronautics and Space Administration (NAG 5‐3952)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Physical Sciences › Environmental Science › Global and Planetary Change › Impact of Light on Environment and Health
- Keywords
- melatonin suppression, phase lag, nocturnal light exposure, circadian rhythm, light-induced phase shift, dim light, chronobiology
- MeSH terms
- Adaptation, Physiological, Adolescent, Adult, Circadian Rhythm, Darkness, Female, Heart Rate, Humans, Light, Male, Melatonin, Photic Stimulation, Sleep, Young Adult, Healthy Volunteers
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