Finding a Research Path for the Identification of Biomarkers of Sleepiness

Sleep disorders and sleep deprivation are an important cause of morbidity and mortality in the United States and worldwide.1 As a consequence, billions of dollars are spent each year on the direct costs of sleep disorders and sleep deprivation. These medical costs include expenses associated with doctor visits, hospital services, prescriptions, and over the counter medications. The indirect costs associated with sleep disorders and sleep loss also result in billions of dollars of non-productive annual expenditures, including costs associated with illness-related morbidity and mortality, absenteeism, presenteeism, disability, reduction or loss of productivity, industrial and motor vehicle accidents, hospitalization, and increased alcohol consumption. Thus, sleep disorders and sleep deprivation are significant threats to public health and productivity in the United States and worldwide and no signs of abatement are emerging. One barrier to reducing their impact is the failure to recognize on a societal and personal level, the major consequence of sleep deprivation—sleepiness. Division of Sleep Medicine, Brigham and Women’s Hospital and Harvard Medical School Boston, MA Unfortunately, despite the extraordinary advances made by sleep and circadian sciences in recent years, a simple, accurate and relatively inexpensive biomarker to assess sleepiness remains a major challenge. Currently, objective markers of sleepiness are based on difficult to interpret and frequently cumbersome electrophysiologic and/or behavioral tests such as the multiple sleep latency test, psychomotor vigilance test, and pupillometry. Although these tests have proven useful for scientific investigations, they are difficult to use in field studies and would have little practical application in occupational and personal safety scenarios. However, notwithstanding considerable effort, to date no reliable, easy to perform biomarkers of sleepiness have been developed. There is an important need for this technology in several areas: 1) in research field studies of the impact of sleep deprivation in both small and large size cohorts; 2) in clinical and occupational settings where assessment of sleepiness would be considerably useful to objectively validate symptoms of sleepiness and in determining fitness for duty; 3) for personal use where such testing might ultimately provide a means for an individual to determine his/her level of sleepiness and allow self adjustment of medication, analogous to the manner that home glucose testing is used today; and 4) for disease risk stratification in conditions where insufficient sleep has been shown to increase incidence or severity of a disease. In order to highlight the need for further research into identification of sleepiness biomarkers, and to stimulate further investigative efforts in this area, the Division of Sleep Medicine at Harvard Medical School2 hosted a conference on September 21-22, 2010 Boston, MA entitled “Finding a Research Path for the Identification of Biomarkers of Sleepiness.” The conference objectives were the following: Provide an overview of the utility of current instruments to detect and quantify levels of sleepiness including both subjective and objective tools or techniques. Present current research on the use of genomic, proteomic, and molecular approaches to assess sleepiness with the emphasis on how such techniques might be used clinically or for clinical research. Stimulate research into the development of clinically useful biomarkers of sleepiness. This supplement consisting of short articles by the speakers summarizes their presentations. In addition, there are two edited panel discussions consisting of dialog among the speakers and the audience. The first article by Dr. Charles Czeisler is a summary of the keynote address entitled “Impact of Sleepiness on Public Health — Utility of a Biomarker” further emphasizing the importance of recognizing sleepiness in society and why a biomarker would be useful. An article by Dr. Michelle Albert illustrates how biomarkers have been found to be useful in the field of cardiovascular medicine. This is followed by a series of three articles by Drs. Thomas Balkin, James Krueger and colleagues, and Namni Goel and David Dinges discussing current behavioral, electrophysiologic and genetic markers of sleepiness, concluding with a panel discussion on the “Current Status of Measuring Sleepiness.” After the panel discussion, is an article by Dr. Paul Shaw and colleagues describing changes in gene expression in Drosophila as a model for identifying relevant gene expression changes in humans after sleep deprivation. This is followed by articles by Dr. Michelle Miller on the association of inflammatory markers with sleepiness and Dr. Krueger and colleagues on the biochemical regulation of sleep. The potential utility of proteonomic and genomic techniques for identification of a sleepiness biomarker is outlined by Drs. Nirinjini Naidoo and George Church. An additional article by Dr. Giovanna Carpagnano, who was scheduled to speak but who was subsequently unable to attend, on use of exhaled breath analysis as a technique for biomarker identification is included as well. The supplement concludes with a second panel discussion focused on answering the question “Can There Be a Biomarker for Sleepiness?” Not included in the supplement are articles from two other speakers, Drs. Robin Farias-Eisner and Edward Haeggstrom on Biomarkers and Cancer — Lessons for Sleep Research and Traffic and work safety: Nonlinear Transient Analysis to Enhance a Posturographic Sleepiness. However, abstracts of their presentations as well as the agenda for the entire conference can be found at http://sleep.med.harvard.edu/what-we-do/biomarkers-conference. With this background, it is the hope of conference organizers and sponsors that awareness of societal and personal impact of sleepiness is heightened and that there is an acceleration of research into identifying biomarkers of sleepiness.