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. 2009 Jun;4(2):165-177.
doi: 10.1016/j.jsmc.2009.01.004.

Effect of Light on Human Circadian Physiology

Effect of Light on Human Circadian Physiology

Jeanne F Duffy et al. Sleep Med Clin. 2009 Jun.

Abstract

The circadian system in animals and humans, being near but not exactly 24-hours in cycle length, must be reset on a daily basis in order to remain in synchrony with external environmental time. This process of entrainment is achieved in most mammals through regular exposure to light and darkness. In this chapter, we review the results of studies conducted in our laboratory and others over the past 25 years in which the effects of light on the human circadian timing system were investigated. These studies have revealed, how the timing, intensity, duration, and wavelength of light affect the human biological clock. Our most recent studies also demonstrate that there is much yet to learn about the effects of light on the human circadian timing system.

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Conflict of interest statement

Financial disclosure

Dr. Duffy reports no conflicts of interest. Dr. Czeisler has received consulting fees from or served as a paid member of scientific advisory boards for: Actelion, Ltd.; Avera Pharmaceuticals, Inc.; Axon Labs, Inc.; Cephalon, Inc.; Delta Airlines; Eli Lilly and Co.; Fedex Kinko’s; Garda Inspectorate, Republic of Ireland, Fusion Medical Education, LLC, Hypnion, Inc.; Morgan Stanley; Sanofi-Aventis, Inc.; the Portland Train Blazers; Sleep Multimedia, Inc.; Sleep Research Society (for which Dr. Czeisler served as president); Respironics, Inc.; Koninklijke Philips Electronics, N.V.; Sepracor, Inc.; Somnus Therapeutics, Inc.; Takeda Pharmaceuticals; Vanda Pharmaceuticals, Inc., Vital Issues in Medicine and Warburg-Pincus. Dr. Czeisler also owns an equity interest in Axon Labs, Inc.; Lifetrac, Inc.; Somnus Therapeutics, Inc.; and Vanda Pharmaceuticals, Inc.

Dr. Czeisler has received lecture fees from the Accreditation Council of Graduate Medical Education; Alfresa; Cephalon, Inc.; Clinical Excellence Commission (Australia); Dalhousie University; Duke University Medical Center; Institute of Sleep Health Promotion (NPO); London Deanery; Morehouse School of Medicine; Sanofi-Aventis, Inc.; Takeda; Tanabe Seiyaku Co., Ltd.; Tokyo Electric Power Company (TEPCO).

Dr. Czeisler has also received clinical trial research contracts from Cephalon, Inc., Merck & Co., Inc., and Pfizer, Inc.; an investigator-initiated research grant from Cephalon, Inc.; and his research laboratory at the Brigham and Women’s Hospital has received unrestricted research and education funds and/or support for research expenses from Cephalon, Inc., Koninklijke Philips Electronics, N.V., ResMed, and the Brigham and Women’s Hospital.

The Harvard Medical School Division of Sleep Medicine (HMS/DSM), which Dr. Czeisler directs, has received unrestricted research and educational gifts and endowment funds from: Boehringer Ingelheim Pharmaceuticals, Inc., Cephalon, Inc., George H. Kidder, Esq., Gerald McGinnis, GlaxoSmithKline, Herbert Lee, Hypnion, Jazz Pharmaceuticals, Jordan’s Furniture, Merck & Co., Inc., Peter C. Farrell, Ph.D., Pfizer, ResMed, Respironics, Inc., Sanofi-Aventis, Inc., Sealy, Inc., Sepracor, Inc., Simmons, Sleep Health Centers LLC, Spring Aire, Takeda Pharmaceuticals, Tempur-Pedic, Aetna US Healthcare, Alertness Solutions, Inc., Axon Sleep Research Laboratories, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Catalyst Group, Cephalon, Inc., Clarus Ventures, Comfortaire Corporation, Committee for Interns and Residents, Farrell Family Foundation, George H. Kidder, Esq., GlaxoSmithKline, Hypnion, Inc., Innovative Brands Goup, Nature’s Rest, Jordan’s Furniture, King Koil Sleep Products, King Koil, Division of Blue Bell Mattress, Land and Sky, Merck Research Laboratories, MPM Capital, Neurocrine Biosciences, Inc., Orphan Medical/Jazz Pharmaceuticals, Park Place Corporation, Pfizer Global Pharmaceuticals, Pfizer Healthcare Division, Pfizer, Inc., Pfizer/Neurocrine Biosciences, Inc., Purdue Pharma L. P., ResMed, Inc., Respironics, Inc., Sanofi-Aventis, Inc., Sanofi-Synthelabo, Sealy Mattress Company, Sealy, Inc., Sepracor, Inc., Simmons Co., Sleep Health Centers LLC, Spring Air Mattress Co., Takeda Pharmaceuticals, Tempur-Pedic Medical Division, Total Sleep Holdings, Vanda Pharmaceuticals, Inc., and the Zeno Group, together with gifts from many individuals and organizations through an annual benefit dinner.

The HMS/DSM Sleep and Health Education Program has received Educational Grant funding from Cephalon, Inc., Takeda Pharmaceuticals, Sanofi-Aventis, Inc. and Sepracor, Inc.

Dr. Czeisler is the incumbent of an endowed professorship provided to Harvard University by Cephalon, Inc. and holds a number of process patents in the field of sleep/circadian rhythms (e.g., photic resetting of the human circadian pacemaker). Since 1985, Dr. Czeisler has also served as an expert witness on various legal cases related to sleep and/or circadian rhythms.

Figures

Figure 1
Figure 1
Phase response curve to a single 6.5-hour episode of bright light in young adults. Phase shifts (in hours) of the plasma melatonin rhythm are plotted with respect to the circadian phase at which the center of the 6.5-hour light stimulus was presented. By convention, phase delay shifts (shifts to a later hour) are plotted as negative numbers, while phase advance shifts (shifts to an earlier hour) are plotted as positive numbers. Phase shift magnitude was determined by assessing phase before and after the light stimulus. Circadian phase of the light stimulus was defined relative to the midpoint of the plasma melatonin rhythm (defined as 22h) assessed just prior to the stimulus. Data from circadian phase 6–18 are double-plotted for better visualization. The open circle represents a subject whose phase shift was determined using salivary melatonin. The solid line represents a best-fit dual harmonic function to the data points. The dashed horizontal line represents the assumed 0.54-hour average phase delay drift of the human circadian pacemaker between the pre- and post-stimulus phase assessments. Figure reproduced with permission from Reference 42 [Khalsa SBS, Jewett ME, Cajochen C, and Czeisler CA. A phase response curve to single bright light pulses in human subjects. J Physiol (Lond) 2003; 549(Pt 3):945–952].
Figure 2
Figure 2
Phase shifts (panel A) and melatonin suppression (Panel B) in response to a 3-cycle 5-hour light stimulus in young adults. The magnitude of the phase shift (in hours) is plotted with respect to the illuminance of the light stimulus (in lux). Symbols represent mean (± s.e.m.) responses from each group of 7–9 subjects. The solid line represents a 3-paramater logistic curve fit to the data, and the upper and lower 95% confidence intervals of this fit are shown in the dashed lines. Figure reproduced with permission from Reference 63 [Zeitzer JM, Khalsa SB, Boivin DB, Duffy JF, Shanahan TL, Kronauer RE, and Czeisler CA. Temporal dynamics of late-night photic stimulation of the human circadian timing system. Am J Physiol 2005; 289(3):R839–R844].
Figure 3
Figure 3
Phase resetting responses to a 3-cycle 5-hour stimulus in young adults. The magnitude of the phase shift (in hours) is plotted with respect to the relative duration of the bright light exposure. The 0% group was exposed to complete darkness throughout the 5-hour stimulus and the 100% group was exposed to continuous bright light throughout the stimulus. Two groups received intermittent bright light exposure during the 5-hour stimulus: 5.3 minutes of bright light interspersed with 19.7 minutes of darkness (31% relative duration group); or 46 minutes of bright light interspersed with 44 minutes of darkness (63% relative duration group). Each point represents the response from 1 subject, and the horizontal bars represent the median phase shift for the group. Figure reproduced with permission from Reference 70 [Rimmer DW, Boivin DB, Shanahan TL, Kronauer RE, Duffy JF, and Czeisler CA. Dynamic resetting of the human circadian pacemaker by intermittent bright light. Am J Physiol 2000; 279(5):R1574–R1579]

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