Tremendous progress in the past few years has led to the identification of several circadian clock genes. This now makes it possible to determine how alterations of human circadian clock genes, and their expression, could lead to differences in circadian and sleep/wake cycle phenotypes. Of particular interest for understanding genetics of the human circadian system are individuals with sleep phase disorders, such as delayed sleep phase syndrome (DSPS) and advanced sleep phase syndrome (ASPS), because recent studies indicate a genetic basis for these disorders. While it is assumed that both ASPS and DSPS are disorders of circadian timing, little is known about how the circadian clock system, or its interaction with sleep processes, are affected in these individuals. Therefore, one of the overall objectives of the proposed studies is to determine the properties (e.g., phase, amplitude, and period) of circadian rhythms under entrained and constant routine conditions in familial ASPS or DSPS. A second objective is to test hypotheses that could explain the mechanisms (i.e., response to light, alterations in period) that underlie the phase disturbance in these conditions. Although it is commonly assumed that sleep per se is normal in the circadian sleep phase disorders, there is some evidence to suggest that the regulation of sleep homeostasis may be altered in DSPS. Therefore, a third specific aim of the proposed studies is to define the sleep-wake characteristics via EEG/polysomnography in DSPS and ASPS subjects during baseline sleep and recovery sleep following sleep deprivation in which the subjects are allowed to begin recovery sleep at a normal or an abnormal circadian time. The approach of studying familial DSPS and ASPS provides a unique opportunity to clearly define circadian and sleep phenotypes in individuals whose sleep/wake cycle is due to intrinsic biological changes and not merely a result of environmental influences and societal pressures. The results of these studies are expected to not only lead to new insights into the regulation of sleep and circadian rhythms in humans, but also to new therapeutic approaches for the treatment of sleep/wake cycle disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL069988-04
Application #
7076267
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Twery, Michael
Project Start
2003-09-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$362,526
Indirect Cost
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Reid, Kathryn J; Baron, Kelly G; Zee, Phyllis C (2014) Meal timing influences daily caloric intake in healthy adults. Nutr Res 34:930-5
Reid, Kathryn J; Santostasi, Giovanni; Baron, Kelly G et al. (2014) Timing and intensity of light correlate with body weight in adults. PLoS One 9:e92251
Baron, Kelly Glazer; Reid, Kathryn J; Horn, Linda Van et al. (2013) Contribution of evening macronutrient intake to total caloric intake and body mass index. Appetite 60:246-251
Reid, Kathryn J; Jaksa, Ashley A; Eisengart, Julie B et al. (2012) Systematic evaluation of Axis-I DSM diagnoses in delayed sleep phase disorder and evening-type circadian preference. Sleep Med 13:1171-7
Zhu, Lirong; Zee, Phyllis C (2012) Circadian rhythm sleep disorders. Neurol Clin 30:1167-91
Turek, Fred W; Vitaterna, Martha Hotz (2011) Molecular neurobiology of circadian rhythms. Handb Clin Neurol 99:951-61
Baron, Kelly G; Reid, Kathryn J; Kern, Andrew S et al. (2011) Role of sleep timing in caloric intake and BMI. Obesity (Silver Spring) 19:1374-81
Dodson, Ehren R; Zee, Phyllis C (2010) Therapeutics for Circadian Rhythm Sleep Disorders. Sleep Med Clin 5:701-715
Chang, Anne-Marie; Reid, Kathryn J; Gourineni, Ramadevi et al. (2009) Sleep timing and circadian phase in delayed sleep phase syndrome. J Biol Rhythms 24:313-21
Reid, Kathryn J; Zee, Phyllis C (2009) Circadian rhythm disorders. Semin Neurol 29:393-405

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