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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 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 (up) 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:22188742 Approved no
Call Number IDA @ john @ Serial 301
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Author Kayumov, L.; Casper, R.F.; Hawa, R.J.; Perelman, B.; Chung, S.A.; Sokalsky, S.; Shapiro, C.M.
Title Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work Type Journal Article
Year 2005 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 90 Issue 5 Pages 2755-2761
Keywords Lighting; Adult; *Circadian Rhythm; Female; Humans; *Light; Male; Melatonin/*secretion; *Work Schedule Tolerance
Abstract Decreases in melatonin production in human and animals are known to be caused by environmental lighting, especially short-wavelength lighting (between 470 and 525 nm). We investigated the novel hypothesis that the use of goggles with selective exclusion of all wavelengths less than 530 nm could prevent the suppression of melatonin in bright-light conditions during a simulated shift-work experiment. Salivary melatonin levels were measured under dim (<5 lux), bright (800 lux), and filtered (800 lux) light at hourly intervals between 2000 and 0800 h in 11 healthy young males and eight females (mean age, 24.7 +/- 4.6 yr). The measurements were performed during three nonconsecutive nights over a 2-wk period. Subjective sleepiness was measured by self-report scales, whereas objective performance was assessed with the Continuous Performance Test. All subjects demonstrated preserved melatonin levels in filtered light similar to their dim-light secretion profile. Unfiltered bright light drastically suppressed melatonin production. Normalization of endogenous melatonin production while wearing goggles did not impair measures of performance, subjective sleepiness, or alertness.
Address Sleep Research Laboratory, Department of Psychiatry, University Health Network, ECW 3D-035, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. lkayumov@uhnres.utoronto.ca
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 (up) 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:15713707 Approved no
Call Number LoNNe @ kagoburian @ Serial 640
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Author Cajochen, C.; Munch, M.; Kobialka, S.; Krauchi, K.; Steiner, R.; Oelhafen, P.; Orgul, S.; Wirz-Justice, A.
Title High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light Type Journal Article
Year 2005 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 90 Issue 3 Pages 1311-1316
Keywords Human Health; Adult; Body Temperature Regulation/physiology/*radiation effects; Circadian Rhythm/physiology/radiation effects; Color; Heart Rate/physiology/*radiation effects; Humans; *Light; Male; Melatonin/*metabolism; Retinal Cone Photoreceptor Cells/physiology; Sleep Stages/physiology/radiation effects; Wakefulness/physiology/*radiation effects
Abstract Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.
Address Centre for Chronobiology, Psychiatric University Clinic, Wilhelm Kleinstr. 27, CH-4025 Basel, Switzerland. christian.cajochen@pukbasel.ch
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 (up) 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:15585546 Approved no
Call Number LoNNe @ kagoburian @ Serial 728
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Author Lockley, S.W.; Brainard, G.C.; Czeisler, C.A.
Title 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 (up) 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:12970330 Approved no
Call Number LoNNe @ kagoburian @ Serial 778
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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 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 (up) 0022-3751 ISBN Medium
Area Expedition Conference
Notes PMID:23090946; PMCID:PMC3630790 Approved no
Call Number IDA @ john @ Serial 239
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