Comparisons of the Variability of Three Markers of the Human Circadian Pacemaker

Journal of Biological Rhythms - Tập 17 Số 2 - Trang 181-193 - 2002
Elizabeth B. Klerman1, Hayley B. Gershengorn2, Jeanne F. Duffy3, Richard E. Kronauer2
1Division of Sleep Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Sleep Medicine, Brigham and Women's Hospital, 221 Long-wood Avenue, Boston, MA 02115, USA
2Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
3Division of Sleep Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA

Tóm tắt

A circadian pacemaker within the central nervous system regulates the approximately 24-h physiologic rhythms in sleep cycles, hormone secretion, and other physiologic functions. Because the pacemaker cannot be examined directly in humans, markers of pacemaker function must be used to study the pacemaker and its response to environmental stimuli. Core body temperature (CBT), plasma cortisol, and plasma melatonin are three marker variables frequently used to estimate the phase of the human pacemaker. Measurements of circadian phase using markers can contain variability due to the circadian pacemaker itself, the intrinsic variability of the marker relative to the pacemaker, the method of analysis of the marker, and the marker assay. For this report, we compared the mathematical variability of a number of methods of identifying circadian phase from CBT, plasma cortisol, and plasma melatonin data collected in a protocol in which pacemaker variability was minimized using low light levels and regular timing of both the light pattern and the rest/activity schedule. We hoped to assess the relative variabilities of the different physiological markers and the analysis methods. Methods were based on the crossing of an absolute threshold, on the crossing of a relative threshold, or on fitting a curve to all data points. All methods of calculating circadian phase from plasma melatonin data were less variable than those calculated using CBT or cortisol data. The standard deviation for the phase estimates using CBT data was 0.78 h, using cortisol data was 0.65 h, and for the eight analysis methods using melatonin data was 0.23 to 0.35 h. While the variability for these markers might be different for other subject populations and/or less stringent study conditions, assessment of the intrinsic variability of the different calculations of circadian phase can be applied to allow inference of the statistical significance of phase and phase shift calculations, as well as estimation of sample size or statistical power for the number of subjects within an experimental protocol.

Từ khóa


Tài liệu tham khảo

10.1097/00001756-199803300-00002

10.1038/379540a0

Boivin DB, 1995, Journal of Sleep Research, 5, S20

10.1177/074873049200700301

Campbell SS, 1993, Sleep, 16, 638

Czeisler CA, 1995, Circadian Clocks and Their Adjustment, 254

10.1126/science.284.5423.2177

Czeisler CA, 2000, Principles and Practice of Sleep Medicine, 353

10.3109/07420529209064548

10.1016/0304-3940(94)91059-6

Deacon SJ, 1993, Melatonin and the Pineal Gland: From Basic Science to Clinical Application, 387

Duffy JF, 1993, Encyclopedia of Sleep and Dreaming, 134

10.1113/jphysiol.1996.sp021593

Hughes RJ, 1998, Sleep, 21, 52

Illnerová H, 1991, Suprachiasmatic Nucleus: The Mind's Clock, 197

10.1038/350059a0

Kittrell EMW, 1991, Suprachiasmatic Nucleus: The Mind's Clock, 233

Klerman EB, 2001, Zeitgebers, Entrainment and Masking of the Circadian System, 155

Klerman EB, 1998, Am J Physiol, 274, R991

10.3109/07420528909059144

10.1111/j.1749-6632.1985.tb11815.x

10.1046/j.1365-2869.1996.d01-67.x

Moore-Ede MC, 1982, The Clocks That Time Us: Physiology of the Circadian Timing System

Ritz-De Cecco A, 1999, Sleep Research Online, 2, 620

Shanahan TL (1995) Circadian physiology and the plasma melatonin rhythm in humans. Harvard Medical School, M.D. honor thesis.

10.1210/jcem-73-2-227

10.1053/sper.2000.9123

10.1177/074873099129000560

10.1210/jcem-71-2-452

10.1177/074873049701200507

10.1177/074873001129002060

Wyatt JK, 1999, Am J Physiol, 277, R1152

10.1016/S0002-9343(99)00266-1

Thông tin
Thông tin xuất bản

Journal of Biological Rhythms

Tập 17 Số 2

181-193

Thông tin tác giả