Abstract
BackgroundAlthough sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioinformatics analyses to explore candidate gene expression biomarkers associated with total sleep deprivation (TSD), and more specifically, the phenotype of neurobehavioral impairment from TSD. Healthy adult volunteers were recruited to a sleep laboratory for seven consecutive days (six nights). After two Baseline nights of 10 h time in bed, 11 subjects underwent an Experimental phase of 62 h of continuous wakefulness, followed by two Recovery nights of 10 h time in bed. Another six subjects underwent a well-rested Control condition of 10 h time in bed for all six nights. Blood was drawn for measuring gene expression on days two, four, and six at 4 h intervals from 08:00 to 20:00 h, corresponding to 12 timepoints across one Baseline, one Experimental, and one Recovery day.ResultsAltogether 212 genes changed expression in response to the TSD Treatment, with most genes exhibiting down-regulation during TSD. Also, 28 genes were associated with neurobehavioral impairment as measured by the Psychomotor Vigilance Test. The results support previous findings associating TSD with the immune response and ion signaling, and reveal novel candidate biomarkers such as the Speedy/RINGO family of cell cycle regulators.ConclusionsThis study serves as an important step toward understanding gene expression changes during sleep deprivation. In addition to exploring potential biomarkers for TSD, this report presents novel candidate biomarkers associated with lapses of attention during TSD. Although further work is required for biomarker validation, analysis of these genes may aid fundamental understanding of the impact of TSD on neurobehavioral performance.
Highlights
Sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans
Statistical models confirmed a significant effect of the total sleep deprivation (TSD) Treatment on Psychomotor Vigilance Test (PVT) lapses (Figs. 1 and 2, Additional file 2: Supplementary text)
Model selection by the lowest AIC and BIC scores preferred models including a Treatment by Phase interaction (χ2 = 21, df = 2, P = 2.58E-05; Fig. 2 Mean (± 1 SE) Psychomotor Vigilance Test (PVT) lapses
Summary
Sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. Neurobehavioral tests have revealed assorted forms of performance deficits from sleep loss, including impairment of learning and of responses to feedback in decision making [3, 6, 7]. Since its introduction over 30 years ago, Besides neurobehavioral testing, efforts have been made to identify molecular biomarkers such as differentially expressed genes or metabolites affected by sleep loss [11,12,13,14,15,16,17]. Beyond identifying the mere presence of a process or response, many biomarkers such as differentially expressed genes can provide mechanistic insights. Surprisingly little effort has been made to synthesize molecular biomarker research with results from neurobehavioral assays
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