Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults.
Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN).



Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8-35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy.



All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry.



Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep.
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.|Sleep Disorders Center, CHU and FMTS, CNRS-UPR 3212, Institute of Cellular and Integrative Neurosciences, University of Strasbourg, Strasbourg, France.|Center for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
Wisse P
WP
van der Meijden
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.|Barlaeus Gymnasium, Amsterdam, The Netherlands.
Jamie L
JL
Van Someren
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.
Bart H W
BH
Te Lindert
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.
Jessica
J
Bruijel
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.|Amsterdam Sleep Center, MC Slotervaart, Amsterdam, The Netherlands.
Floor
F
van Oosterhout
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.
Joris E
JE
Coppens
Netherlands Institute for Neuroscience, Dept. Hypothalamic Integration Mechanisms, Amsterdam, The Netherlands.|Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Andries
A
Kalsbeek
Center for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
Christian
C
Cajochen
Sleep Disorders Center, CHU and FMTS, CNRS-UPR 3212, Institute of Cellular and Integrative Neurosciences, University of Strasbourg, Strasbourg, France.
Patrice
P
Bourgin
Netherlands Institute for Neuroscience, Department of Sleep and Cognition, Amsterdam, The Netherlands.|Departments of Integrative Neurophysiology and Medical Psychology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, the Netherlands.
Eus J W
EJ
Van Someren
D056044:Actigraphy; D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D003116:Color; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007206:Individuality; D008027:Light; D055537:Light Signal Transduction / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D010775:Photic Stimulation; D066250:Pretectal Region / Q000502:physiology / Q000528:radiation effects; D011680:Pupil / Q000502:physiology / Q000528:radiation effects; D012160:Retina / Q000502:physiology / Q000528:radiation effects; D017299:Rod Opsins / Q000378:metabolism*; D057566:Self Report; D012890:Sleep / Q000502:physiology* / Q000528:radiation effects; D013493:Suprachiasmatic Nucleus / Q000502:physiology / Q000528:radiation effects; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult; D000099210:Melanopsin
D017299:Rod Opsins; D000099210:Melanopsin
circadian; light; melanopsin; post-illumination pupil response; sleep timing