Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults
van der Meijden, Wisse P. ; Van Someren, Jamie L. ; te Lindert, Bart H.W. ; Bruijel, Jessica ; van Oosterhout, Floor ; Coppens, Joris E. ; Kalsbeek, Andries ; Cajochen, Christian ; Bourgin, Patrice ; Van Someren, Eus J.W.
In: Sleep, 2016, vol. 39, no. 6, p. 1305-1310
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- Abstract Study Objectives: 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). Methods: 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. Results: 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. Conclusions: 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. Significance Biological mechanisms underlying individual differences in sleep timing are insufficiently understood. We show an association of individual differences in sleep timing with specific functionality of melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). Focusing on adolescents and young adults, an age range with known vulnerability to a delayed sleep phase, we measured the post-illumination pupil response after blue light. This measure of intrinsic ipRGC functionality was consistently associated with three independent measures of sleep timing (i.e., a chronotype questionnaire, a sleep diary, and actigraphy). Individuals with a later sleep timing had a stronger intrinsic ipRGC responsiveness to blue light. Clinical interventions for delayed sleep phase syndrome may benefit from considering hypersensitivity to blue light.