United States Department of Transportation
i
Gene Expression Biomarkers of the Response To Sleep Loss With and Without Modafinil
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2023-09-01
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[PDF-2.04 MB]
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Abstract:Sleep disruption presents a substantial risk to health and safety, particularly due to the risks of performance degradation in safety-critical operations that can result in catastrophic injuries or mortality. Federal regulations exist to minimize the risks of fatigue with limitations on hours worked and requirements for fatigue risk management plans. Yet, even with workload controls and scheduled opportunities for rest, fatigue may be caused by factors such as personal and lifestyle choices, illness, and circadian disruption from travel across multiple time zones. Complicating risk mitigation is the challenge of identifying and measuring fatigue. Here, we report on gene expression biomarkers (biological indicators) for cognitive impairment during sleep loss. We observe hundreds of genes whose expression is associated with attention changes during one night of sleep loss. Several genes are identified that we previously associated with attention impairment in a separate study of sleep loss. The reproducibility of findings may indicate the robustness of these candidate fatigue impairment biomarkers. However, some biomarker genes only associate with certain tests of impairment (e.g., attention lapses but not self-reported fatigue), suggesting that different biomarker panels may be developed to assess the particular cognitive domains that need monitoring for a given safety critical operation. We also find that using a drug countermeasure (modafinil) not only helps mitigate impairment on tests of attention lapses, but also disrupts gene expression associations with attention lapses. Further research is needed to confirm whether this represents a unique effect of modafinil administration, or emphasizes the need to ensure biomarker validation occurs both in the presence and absence of countermeasures.
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