ReviewCircadian rhythms and sleep in children with autism
Introduction
Many children with autism suffer some form of sleep disturbance (Richdale, 1999). Although the consequences of sleep problems have been more extensively studied in adults, sleep loss in children and adolescents has been associated with daytime sleepiness and impaired performance at school (Meijer et al., 2000, Wolfson and Carskadon, 2005). Furthermore, parents of children with autism report their own sleep is disrupted as a result of their child's sleeping patterns (Polemini et al., 2005). Negative consequences of sleep disturbance could therefore also threaten the efficacy of behavioral treatments for children with autism, both in terms of performance of the child as well as the ability of the parents to properly employ learned treatment strategies and techniques.
Increased sleep latencies, waking during the night and difficulty awakening in the morning are among the most frequently reported problems (Patzold et al., 1998, Richdale and Prior, 1995, Wiggs and Stores, 2004, Williams et al., 2004), resulting in less overall total sleep. Such abnormalities suggest that the sleep problems may represent a circadian disturbance in the daily timing of neurobehavioral and endocrine functions. This theory is supported by limited information regarding abnormal cortisol and melatonin profiles in children with autism (Corbett et al., 2006, Corbett et al., 2008, Curin et al., 2003, Kulman et al., 2000, Richdale and Prior, 1992, Ritvo et al., 1993, Tordjman et al., 1997, Tordjman et al., 2005). Although recent efficacy studies of melatonin treatment to correct sleep in these children are based on impairment of the circadian system (Andersen et al., 2008, Paavonen et al., 2003), few published reports have thoroughly examined the putative association between sleep disturbance and circadian rhythms in autism (Richdale, 1999). Furthermore, sleep and hormonal patterns in autism have not been examined within the context of normal development of circadian rhythms nor have current models of sleep been applied as a framework for considering the most common sleep problems in these children. The goal of this paper is to characterize what is currently known about sleep and circadian rhythms as a way to gain insight into the sleep disturbance often reported in children with autism.
Section snippets
Sleep and circadian rhythms
A well recognized model of sleep posits that there are two principle modulators of sleep and wakefulness: sleep homeostasis and the circadian pacemaker (Borbély, 1982, Borbély et al., 1989; see Fig. 1). Under normal conditions, relative coordination of the sleep homeostatic and circadian systems is what accounts for a typical daily schedule in adults, with 16 h of constant wakefulness during the day and 8 h of consolidated sleep at night (Dijk and Czeisler, 1995).
Sleep homeostasis is a regulatory
Circadian sleep disorders
Normal patterns of sleep and circadian rhythms may become disrupted as a result of a misalignment between the circadian system and the sleep–wake cycle or via direct impairment of circadian functioning. A hallmark characteristic of most circadian sleep disorders is the inability to sleep during desired times, with common complaints of difficulty in initiating or maintaining sleep, early awakening and/or impaired alertness during waking hours. Interestingly, these are also among the most common
Sleep and circadian rhythms in children with autism
Some have conjectured that the frequently reported sleep problems in children with autism may be due to a circadian disturbance (Patzold et al., 1998, Richdale and Prior, 1995). Yet published reports examining the putative relationship between sleep disturbance and circadian rhythms in children with autism have been limited (Richdale, 1999). A current review of the literature is timely due to a subsequent surge in studies confirming and refining those earlier insights. Still, speculation of
Relationship of melatonin to sleep and circadian rhythms
One of the best markers of the human circadian pacemaker is the pineal hormone melatonin rhythm. The natural light–dark cycle entrains the rhythmic synthesis and secretion of melatonin via a neural pathway separate from the visual system, called the retinohypothalamic tract (RHT) (Klein et al., 1991, Moore, 1983). In all species, including humans, melatonin secretion is high at night and low during the day (Arendt, 1995, Tamarkin et al., 1980). Specifically, in individuals normally entrained to
Hormone profiles in children with autism
Neuroendocrine markers provide additional circadian endpoints that are less subject to social influences. Both cortisol and melatonin levels have been quantified in children with autism via sampling of blood, urine and saliva. Known studies of hormones and autism will be described in order to assess what are likely to be the most reliable findings. Better understanding of these overt rhythms in children with autism will provide an important clue in determining the circadian contribution to the
Impairments in entrainment
Alterations in sleep and hormonal rhythms in children with autism may, in theory, be due to impairment of entrainment mechanisms. Children with autism are subject to many variables that could potentially impact usual signals of entrainment, including hyper- and hypo-sensitivities to visual and auditory stimuli (Talay-Ongan and Wood, 2000), decreased attention to social cues (Dawson et al., 1998), and possible misalignment between circadian phase and light–dark cycles (as described earlier).
Development of sleep and circadian rhythms
The development of a mature sleep–wake rhythm is a fairly well described process. Importantly, there is a rather large range of what is to be considered normal childhood sleep behavior. Likewise, significant individual differences have been reported in development of circadian rhythms, both in pre-term and full-term infants (Kennaway et al., 1992, Mirmiran and Kok, 1991, Sadeh, 1997). This section will rely heavily on generalities derived from multiple studies. Examining the timing of the
Suggestions
Sleep disturbance can be a rather serious problem that requires identification of causal factors in order to develop appropriate treatment methods. Because there are many variables to consider within the complexities of both sleep and autism, it is challenging to interpret existing data as well as design studies that are going to yield meaningful information. Sleep problems most commonly reported in children with autism are now considered within the context of the Borbély two-process model,
Summary
Chronic decrements in sleep lead to a variety of problems, regardless of the cause (Dinges, 2006, for review). It has been hypothesized that sleep disturbance may even predict autistic behaviors throughout the day (Schreck et al., 2004). This review has focused primarily on circadian disturbances because these appear to represent a large proportion of all reported problems in children with autism, based on similar patterns to well established circadian sleep disorders. Furthermore, current
Conclusion
There is value to exploring the dynamic relationship between circadian rhythms and sleep via established models, recognized pathologies and as a normal course of development in order to gain further insight into the potential relevance to children with autism. It is now necessary to examine sleep studies in children with autism, with consideration of circadian influences, in an effort to better understand the underlying mechanisms and minimize the negative impact of these disturbances on both
Acknowledgements
Special thanks to Michael Gorman for his critical reading of multiple drafts of the article. Further thanks to Aaron Steckelberg for helping to develop the Figures. Lastly, I would also like to acknowledge Laura Schreibman, Stephan Anagnastoras, and Lauren McNulty for constructive comments on an earlier version.
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