Analysis method and experimental conditions affect computed circadian phase from melatonin data

Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of...

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Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e33836-e33836
Main Authors: Klerman, Hadassa, St Hilaire, Melissa A, Kronauer, Richard E, Gooley, Joshua J, Gronfier, Claude, Hull, Joseph T, Lockley, Steven W, Santhi, Nayantara, Wang, Wei, Klerman, Elizabeth B
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Biology
Biomarkers - blood
Body temperature
Circadian Rhythm
Circadian Rhythm Signaling Peptides and Proteins - metabolism
Circadian rhythms
Comparative analysis
Computer Science
Curve fitting
Data collection
Data loss
Differential equations
Estimates
Hospitals
Humans
Insomnia
Laboratories
Life Sciences
Light
Mathematical models
Medical schools
Medicine
Melatonin
Melatonin - blood
Methods
Middle Aged
Missing data
Models, Biological
Offsets
Older people
Secretion
Set theory
Sleep
Variability
Womens health
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Summary:Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based and physiologically-based linear differential equations. To determine which method provides the most accurate assessment of circadian phase, we compared the ability to fit the data and the variability of phase estimates for seventeen different markers of melatonin phase derived from these methodological categories. We used data from three experimental conditions under which circadian rhythms - and therefore calculated melatonin phase - were expected to remain constant or progress uniformly. Melatonin profiles from older subjects and subjects with lower melatonin amplitude were less likely to be fit by all analysis methods. When circadian drift over multiple study days was algebraically removed, there were no significant differences between analysis methods of melatonin onsets (P = 0.57), but there were significant differences between those of melatonin offsets (P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0033836