Delayed sleep phase disorder, circadian genes, sleep homeostasis and light sensitivity

© Cambridge University Press 2013.In humans, the sleep–wake cycle is determined by the interaction of the endogenous circadian clock and sleep homeostat, and exogenous factors such as the light/dark cycle, which is important for circadian entrainment, and social influences such as work and recreation (Figure 31.1). These factors interact and it is often difficult to determine the causes and nature of altered sleep–wake timing. Abnormal sleep–wake timing may be a simple consequence of an abnormal phase relationship of the circadian clock and environmental time. This may be caused by aberrant light exposure patterns or extreme intrinsic periods of the circadian clock. The timing of the sleep–wake cycle relative to the circadian sleep propensity rhythm may be altered because of fast or slow build-up of homeostatic sleep pressure. Recent mathematical models of the sleep–wake cycle have indeed demonstrated that one particular phenotype may be related to parameters of very different processes [1]. Here, we focus on some of the genetic factors that are associated with abnormally delayed sleep timing, and explore to what extent the effects of these factors can be attributed to physiological processes such as light sensitivity, sleep homeostasis or circadian period. Circadian rhythm sleep disorders (CRSDs) refer to sleep disturbances that are primarily due to alterations of the circadian time-keeping system or are related to a misalignment of endogenous circadian rhythms and the required sleep–wake time (see [2]). The latter distinction is important because social factors may necessitate a non-desirable sleep–wake schedule, as occurs in shift work, for example. Shift work disorder and jet lag disorder are CRSDs that are caused by exogenous factors, whereas dysfunction of the endogenous circadian clock is thought to be the primary cause of delayed sleep phase disorder (DSPD). A better understanding of what causes CRSDs and inter-individual vulnerability differences is important because of the large proportion of the population who regularly undertake shift work, the epidemiological evidence linking insufficient sleep with negative health outcomes [3], and known associations between extreme evening preference and health problems such as mood disorders, metabolic disorders, and cardiovascular risk (see [4])