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Author Lockley, S.W.; Brainard, G.C.; Czeisler, C.A.
Title (up) High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light Type Journal Article
Year 2003 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 88 Issue 9 Pages 4502-4505
Keywords Human Health; Adult; Area Under Curve; Circadian Rhythm/*radiation effects; Female; Humans; *Light; Male; Melatonin/*metabolism; Pineal Gland/metabolism/radiation effects; Saliva/metabolism; Non-programmatic
Abstract The endogenous circadian oscillator in mammals, situated in the suprachiasmatic nuclei, receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells. The human circadian pacemaker is exquisitely sensitive to ocular light exposure, even in some people who are otherwise totally blind. The magnitude of the resetting response to white light depends on the timing, intensity, duration, number and pattern of exposures. We report here that the circadian resetting response in humans, as measured by the pineal melatonin rhythm, is also wavelength dependent. Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density. Similarly, 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light, and is dependent on the duration of exposure in addition to wavelength. These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system, the sensitivity of which peaks at approximately 555 nm. Thus photopic lux, the standard unit of illuminance, is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker.
Address Division of Sleep Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:12970330 Approved no
Call Number LoNNe @ kagoburian @ Serial 778
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Author Chellappa, S.L.; Viola, A.U.; Schmidt, C.; Bachmann, V.; Gabel, V.; Maire, M.; Reichert, C.F.; Valomon, A.; Gotz, T.; Landolt, H.-P.; Cajochen, C.
Title (up) Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3 Type Journal Article
Year 2012 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 97 Issue 3 Pages E433-7
Keywords Adult; Alleles; Cross-Over Studies; Female; Genotype; Homozygote; Humans; *Light; Male; Melatonin/*blood/genetics; *Minisatellite Repeats; Period Circadian Proteins/*genetics; *Polymorphism, Genetic; Questionnaires; Sleep/genetics; Wakefulness/*genetics
Abstract CONTEXT: Light exposure, particularly at the short-wavelength range, triggers several nonvisual responses in humans. However, the extent to which the melatonin-suppressing and alerting effect of light differs among individuals remains unknown. OBJECTIVE: Here we investigated whether blue-enriched polychromatic light impacts differentially on melatonin and subjective and objective alertness in healthy participants genotyped for the PERIOD3 (PER3) variable-number, tandem-repeat polymorphism. DESIGN, SETTING, AND PARTICIPANTS: Eighteen healthy young men homozygous for the PER3 polymorphism (PER3(5/5)and PER3(4/4)) underwent a balanced crossover design during the winter season, with light exposure to compact fluorescent lamps of 40 lux at 6500 K and at 2500 K during 2 h in the evening. RESULTS: In comparison to light at 2500 K, blue-enriched light at 6500 K induced a significant suppression of the evening rise in endogenous melatonin levels in PER3(5/5) individuals but not in PER3(4/4). Likewise, PER3(5/5) individuals exhibited a more pronounced alerting response to light at 6500 K than PER3(4/4) volunteers. Waking electroencephalographic activity in the theta range (5-7 Hz), a putative correlate of sleepiness, was drastically attenuated during light exposure at 6500 K in PER3(5/5) individuals as compared with PER3(4/4). CONCLUSIONS: We provide first evidence that humans homozygous for the PER3 5/5 allele are particularly sensitive to blue-enriched light, as indexed by the suppression of endogenous melatonin and waking theta activity. Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in the sleep-wake regulation.
Address Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstrasse 27, CH-4012 Basel, Switzerland
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:22188742 Approved no
Call Number IDA @ john @ Serial 301
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Author Ruger, M.; St Hilaire, M.A.; Brainard, G.C.; Khalsa, S.-B.S.; Kronauer, R.E.; Czeisler, C.A.; Lockley, S.W.
Title (up) Human phase response curve to a single 6.5 h pulse of short-wavelength light Type Journal Article
Year 2013 Publication The Journal of Physiology Abbreviated Journal J Physiol
Volume 591 Issue Pt 1 Pages 353-363
Keywords Adolescent; Adult; Body Temperature; Circadian Rhythm/*physiology; Female; Humans; *Light; Male; Melatonin/physiology; Young Adult; blue light; melatonin; photic response; whort-wavelength
Abstract The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a phase response curve (PRC). Previous PRCs in humans have utilized high-intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive to short-wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol. Eighteen young healthy participants (18-30 years) were studied for 9-10 days in a time-free environment. The protocol included three baseline days followed by a constant routine (CR) to assess initial circadian phase. Following this CR, participants were exposed to a 6.5 h 480 nm light exposure (11.8 muW cm(-2), 11.2 lux) following mydriasis via a modified Ganzfeld dome. A second CR was conducted following the light exposure to re-assess circadian phase. Phase shifts were calculated from the difference in dim light melatonin onset (DLMO) between CRs. Exposure to 6.5 h of 480 nm light resets the circadian pacemaker according to a conventional type 1 PRC with fitted maximum delays and advances of -2.6 h and 1.3 h, respectively. The 480 nm PRC induced approximately 75% of the response of the 10,000 lux white light PRC. These results may contribute to a re-evaluation of dosing guidelines for clinical light therapy and the use of light as a fatigue countermeasure.
Address Circadian Physiology Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. mrueger@rics.bwh.harvard.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3751 ISBN Medium
Area Expedition Conference
Notes PMID:23090946; PMCID:PMC3630790 Approved no
Call Number IDA @ john @ Serial 239
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Author Revell, V.L.; Molina, T.A.; Eastman, C.I.
Title (up) Human phase response curve to intermittent blue light using a commercially available device Type Journal Article
Year 2012 Publication The Journal of Physiology Abbreviated Journal J Physiol
Volume 590 Issue Pt 19 Pages 4859-4868
Keywords Adolescent; Adult; Circadian Clocks/physiology/*radiation effects; Female; Humans; *Light; Male; Melatonin/analysis/physiology; Saliva/chemistry; Young Adult; blue light
Abstract Light shifts the timing of the circadian clock according to a phase response curve (PRC). To date, all human light PRCs have been to long durations of bright white light. However, melanopsin, the primary photopigment for the circadian system, is most sensitive to short wavelength blue light. Therefore, to optimise light treatment it is important to generate a blue light PRC.We used a small, commercially available blue LED light box, screen size 11.2 x 6.6 cm at approximately 50 cm, approximately 200 muW cm(-2), approximately 185 lux. Subjects participated in two 5 day laboratory sessions 1 week apart. Each session consisted of circadian phase assessments to obtain melatonin profiles before and after 3 days of free-running through an ultradian light-dark cycle (2.5 h wake in dim light, 1.5 h sleep in the dark), forced desynchrony protocol. During one session subjects received intermittent blue light (three 30 min pulses over 2 h) once a day for the 3 days of free-running, and in the other session (control) they remained in dim room light, counterbalanced. The time of blue light was varied among subjects to cover the entire 24 h day. For each individual, the phase shift to blue light was corrected for the free-run determined during the control session. The blue light PRC had a broad advance region starting in the morning and extending through the afternoon. The delay region started a few hours before bedtime and extended through the night. This is the first PRC to be constructed to blue light and to a stimulus that could be used in the real world.
Address University of Surrey, Guildford, Surrey GU2 7XH, UK
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3751 ISBN Medium
Area Expedition Conference
Notes PMID:22753544; PMCID:PMC3487041 Approved no
Call Number IDA @ john @ Serial 345
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Author Foster, R.G.; Roenneberg, T.
Title (up) Human responses to the geophysical daily, annual and lunar cycles Type Journal Article
Year 2008 Publication Current Biology : CB Abbreviated Journal Curr Biol
Volume 18 Issue 17 Pages R784-R794
Keywords Human Health; Biological Clocks; Birth Rate; Circadian Rhythm; Death; Female; Human Activities; Humans; Male; Moon; *Periodicity; Photoperiod; Seasons; Sexual Behavior; Sleep
Abstract Collectively the daily, seasonal, lunar and tidal geophysical cycles regulate much of the temporal biology of life on Earth. The increasing isolation of human societies from these geophysical cycles, as a result of improved living conditions, high-quality nutrition and 24/7 working practices, have led many to believe that human biology functions independently of them. Yet recent studies have highlighted the dominant role that our circadian clock plays in the organisation of 24 hour patterns of behaviour and physiology. Preferred wake and sleep times are to a large extent driven by an endogenous temporal program that uses sunlight as an entraining cue. The alarm clock can drive human activity rhythms but has little direct effect on our endogenous 24 hour physiology. In many situations, our biology and our society appear to be in serious opposition, and the damaging consequences to our health under these circumstances are increasingly recognised. The seasons dominate the lives of non-equatorial species, and until recently, they also had a marked influence on much of human biology. Despite human isolation from seasonal changes in temperature, food and photoperiod in the industrialised nations, the seasons still appear to have a small, but significant, impact upon when individuals are born and many aspects of health. The seasonal changes that modulate our biology, and how these factors might interact with the social and metabolic status of the individual to drive seasonal effects, are still poorly understood. Lunar cycles had, and continue to have, an influence upon human culture, though despite a persistent belief that our mental health and other behaviours are modulated by the phase of the moon, there is no solid evidence that human biology is in any way regulated by the lunar cycle.
Address Circadian and Visual Neuroscience, Nuffield Laboratory of Ophthalmology, University of Oxford, Levels 5 & 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 7BN, UK. russell.foster@eye.ox.ac.uk
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0960-9822 ISBN Medium
Area Expedition Conference
Notes PMID:18786384 Approved no
Call Number LoNNe @ kagoburian @ Serial 752
Permanent link to this record