Disorders of sleep and circadian rhythms

Abstract

Sleep is fundamental to the survival of humans. However, knowledge regarding the role of sleep and its regulation is poorly understood. Genetics in flies, mice, and humans has led to a detailed understanding of some aspects of circadian regulation. Sleep homeostasis (the effect of increasing periods of wakefulness on our sleep propensity) is largely not understood. Sleep homeostasis is distinct from, but also linked to, the circadian clock. It is only in the last two decades that our understanding of some sleep disorders has been revealed. These breakthroughs were mostly fueled by intensive investigation using genetic tools. Although modern human genetics has revolutionized scientific research of neurologic disorders beginning ~35 years ago, studies of sleep and sleep disorders have lagged behind those of many neurologic diseases. This is due to the complexity in phenotyping behaviors like sleep and the fact that sleep is strongly influenced by environmental and other factors. We have long been aware that the amount of sleep required by individuals is normally distributed in the general population with small proportions of people being natural short or natural long sleepers. However, it has been less than a decade since Mendelian families of natural short sleepers have been recognized. Recent work has made significant advances and mechanistic insights of several sleep disorders as well as familial natural short sleepers by using ever-improving human genetic and cellular molecular tools. Given recent advances into genetic and biologic understanding of sleep, the hope of understanding this indispensable process is closer. Ultimately, our growing understanding will lead to more effective treatments of human sleep disorders.

Keywords: circadian rhythms; human genetics; sleep disorders.