title: Light modulation of human sleep depends on a polymorphism in the clock gene Period3.
abstract: Non-image-forming (NIF) responses to light powerfully modulate human physiology. However, it remains scarcely understood how NIF responses to light modulate human sleep and its EEG hallmarks, and if there are differences across individuals. Here we investigated NIF responses to light on sleep in individuals genotyped for the PERIOD3 (PER3) variable-number tandem-repeat (VNTR) polymorphism. Eighteen healthy young men (20-28 years; mean ± SEM: 25.9 ± 1.2) homozygous for the PER3 polymorphism were matched by age, body-mass index, and ethnicity. The study protocol comprised a balanced cross-over design during the winter, during which participants were exposed to either light of 40 lx at 6,500 K (blue-enriched) or light at 2,500 K (non-blue enriched), during 2h in the evening. Compared to light at 2,500 K, light at 6,500 K induced a significant increase in all-night NREM sleep slow-wave activity (SWA: 1.0-4.5 Hz) in the occipital cortex for PER3(5/5) individuals, but not for PER3(4/4) volunteers. Dynamics of SWA across sleep cycles revealed increased occipital NREM sleep SWA for virtually all sleep episode only for PER3(5/5) individuals. Furthermore, they experienced light at 6,500 K as significantly brighter. Intriguingly, this subjective perception of brightness significantly predicted their increased occipital SWA throughout the sleep episode. Our data indicate that humans homozygous for the PER3(5/5) allele are more sensitive to NIF light effects, as indexed by specific changes in sleep EEG activity. Ultimately, individual differences in NIF light responses on sleep may depend on a clock gene polymorphism involved in sleep-wake regulation.
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland; Cyclotron Research Center, University of Liège, Liège, Belgium.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Chellappa
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Antoine U
authors.initials: AU
authors.lastname: Viola
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bachmann
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gabel
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Micheline
authors.initials: M
authors.lastname: Maire
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Carolin F
authors.initials: CF
authors.lastname: Reichert
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Valomon
authors.affiliation: Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Landolt
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland. Electronic address: Christian.Cajochen@upkbs.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Cajochen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004569:Electroencephalography; D006720:Homozygote; D006801:Humans; D008027:Light; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012890:Sleep / Q000235:genetics*; D012895:Sleep, REM / Q000235:genetics; D055815:Young Adult
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins
keywords: Clock gene polymorphism; Luminance encoding; Non-image-forming system; Sleep EEG activity; Spectral analysis