Vol 9, No 3 - Chronobiology in Psychiatry
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any aspects of human physiology and behavior are dominated by 24-hour rhythms that have a major impact on our health and well-being. For example, sleep- wake cycles, alertness and performance patterns, core body temperature rhythms, and the production of hor- mones such as melatonin and cortisol are all regulated by an endogenous near-24-hour oscillator in the suprachi- asmatic nuclei (SCN) of the anterior hypothalamus.The cells in these nuclei spontaneously generate rhythms with a period close to, but not exactly, 24 hours, and in order for the circadian pacemaker to ensure that physiology and behavior are appropriately timed to anticipate events in the outside world, environmental time cues must be able to reset this internal clock to 24 hours. The major environmental  time  cue  that  resets  these  rhythms  in mammals is the 24-hour light-dark cycle generated by the earth’s  axial  rotation.  Light  information  is  captured exclusively by the eyes using specialized retinal photore- ceptors and transduced directly to the SCN via a dedi- cated  neural  pathway,  the  retinohypothalamic  tract (RHT). Each day the light-dark cycle resets the internal clock, which in turn synchronizes the physiology and behavior controlled by the clock. The major biochemical correlate of the light-dark cycle is provided by the pineal melatonin rhythm. Under nor- mal light-dark conditions, melatonin is produced only C l i n i c a l  r e s e a r c h M Copyright © 2007 LLS SAS.  All rights reserved www.dialogues-cns.org Visual impairment and circadian rhythm disorders Steven W. Lockley, PhD; Josephine Arendt, PhD, FRCPath; Debra J. Skene, PhD Keywords:    blindness;   circadian;   melatonin;   sleep;   alertness;   performance; entrainment; non-24-hour sleep-wake disorder; advanced sleep phase syndro- me; delayed sleep phase syndrome Author affiliations: Division of Sleep Medicine, Brigham and Women’s Hospital, Harvard  Medical  School,  Boston,  Mass,  USA  (Steven  W.  Lockley);  Centre  for Chronobiology,  School  of  Biomedical  and  Molecular  Sciences,  University  of Surrey, Guildford, UK (Josephine Arendt, Debra J. Skene)   Address for correspondence: Steven W. Lockley, PhD, Division of Sleep Medicine, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston MA 02115 USA (e-mail: slockley@hms.harvard.edu) Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance pat- terns, and many daily hormone profiles. These rhythms are  spontaneously  generated  by  an  internal  “pace- maker” in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external envi- ronment. Sighted individuals take this daily synchro- nization process for granted, although they experience some  of  the  consequences  of  circadian  desynchrony when “jetlagged” or working night shifts. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the hypothalamic circadian clock, resulting in cyclical episodes of poor sleep and daytime dysfunction. Daily melatonin administration, which provides a replacement synchronizing daily “time cue,” is a promising therapeutic strategy, although opti- mal treatment dose and timing remain to be deter- mined.    © 2007, LLS SAS Dialogues Clin Neurosci. 2007;9:301-314.