title: Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.
abstract: Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.
authors.affiliation: Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ho Mien
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Eric Chern-Pin
authors.initials: EC
authors.lastname: Chua
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Pauline
authors.initials: P
authors.lastname: Lau
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Luuan-Chin
authors.initials: LC
authors.lastname: Tan
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Ivan Tian-Guang
authors.initials: IT
authors.lastname: Lee
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Sing-Chen
authors.initials: SC
authors.lastname: Yeo
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Sara Shuhui
authors.initials: SS
authors.lastname: Tan
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gooley
mesh_terms: D000328:Adult; D001831:Body Temperature; D002940:Circadian Rhythm / Q000528:radiation effects*; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D010775:Photic Stimulation; D011680:Pupil / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology
chemical_list: D008550:Melatonin; D006854:Hydrocortisone