Review
Circadian rhythms and sleep in children with autism

https://doi.org/10.1016/j.neubiorev.2009.11.017Get rights and content

Abstract

A growing body of research has identified significant sleep problems in children with autism. Disturbed sleep–wake patterns and abnormal hormone profiles in children with autism suggest an underlying impairment of the circadian timing system. Reviewing normal and dysfunctional relationships between sleep and circadian rhythms will enable comparisons to sleep problems in children with autism, prompt a reexamination of existing literature and offer suggestions for future inquiry. In addition, sleep and circadian rhythms continue to change over the course of development even in typical, healthy humans. Therefore, exploring the dynamic relationship between circadian rhythms and sleep throughout development provides valuable insight into those sleep problems associated with autism. Ultimately, a better understanding of sleep and circadian rhythms in children with autism may help guide appropriate treatment strategies and minimize the negative impact of these disturbances on both the children and their families.

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.

References (171)

  • D.-J. Dijk et al.

    Melatonin effect on daytime sleep in men: suppression of EEG low frequency activity and enhancement of séépindle frequency activity

    Neurosci Lett

    (1995)
  • D. Dinges

    The state of sleep deprivation: from functional biology to functional consequences

    Sleep Med Rev

    (2006)
  • M. Diomedi et al.

    Sleep abnormalities in mentally retarded autistic subjects: Down's syndrome with mental retardation and normal subjects

    Brain Dev

    (1999)
  • M. Elia et al.

    Sleep in subjects with autistic disorder: a neurophysiological study

    Brain Dev

    (2000)
  • C. Kirschbaum et al.

    Salivary cortisol in psychoneuroendocrine research: recent developments and applications

    Psychoneuroendocrinology

    (1994)
  • M. Mirmiran et al.

    Influence of light in the NICU on the development of circadian rhythms in preterm infants

    Seminars in Perinatology

    (2000)
  • M. Mirmiran et al.

    Circadian rhythms in early human development

    Early Hum Dev

    (1991)
  • C. Acebo et al.

    Estimating sleep patterns with activity monitoring in children and adolescents: how many nights are necessary for reliable measures?

    Sleep

    (1999)
  • C. Acebo et al.

    Sleep/wake patterns derived from activity monitoring and maternal report for healthy 1–5 year old children

    Sleep

    (2005)
  • P. Achermann et al.

    Mathematical models of sleep regulation

    Front Biosci

    (2003)
  • H. Allik et al.

    Sleep patterns of school-age children with Asperger syndrome or high-functioning autism

    J Autism Dev Disord

    (2006)
  • American College of Physicians-American Society of Internal Medicine

    (PDF: full text). International Classification of Sleep Disorders: Diagnostic & Coding Manual

    (2005)
  • S. Amir et al.

    Resetting of the circadian clock by a conditioned stimulus

    Nature

    (1996)
  • S. Ancoli-Israel et al.

    A pedigree of one family with delayed sleep phase syndrome

    Chronobiol Int

    (2001)
  • T. Anders et al.

    Sleeping through the night: a developmental perspective

    Pediatrics

    (1992)
  • T. Anders et al.

    Normal sleep in neonates and children

  • I. Andersen et al.

    Melatonin for insomnia in children with autism spectrum disorders

    J Child Neurol

    (2008)
  • S. Antonini et al.

    The emergence of salivary cortisol circadian rhythm and its relationship to sleep activity in preterm infants

    Clin Endocrinol

    (2000)
  • H. Aoki et al.

    Hypersensitivity of melatonin suppression in response to light in patients with delayed sleep phase syndrome

    Chronobiol Int

    (2001)
  • S. Archer et al.

    A polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference

    Sleep

    (2003)
  • J. Ardura et al.

    Emergence and evolution of the circadian rhythm of melatonin in children

    Hormone Res

    (2003)
  • J. Arendt

    Melatonin assay in body fluids

    J Neural Transm Suppl

    (1978)
  • J. Arendt

    Melatonin and the Mammalian Pineal Gland

    (1995)
  • J. Aschoff et al.

    Human circadian rhythms in continuous darkness: Entrainment by social cues

    Science

    (1971)
  • A. Beltrami et al.

    Sleep and bedtime behavior in pre-school-aged children

    Pediatrics

    (1983)
  • F. Bes et al.

    The distribution of slow-wave sleep across the night: a comparison for infants, children and adults

    Sleep

    (1991)
  • A. Borbély

    Sleep regulation: circadian rhythm and homeostasis

  • A. Borbély et al.

    Sleep initiation and initial sleep intensity: interaction of homeostatic and circadian mechanisms

    J Biol Rhythms

    (1989)
  • Z. Boulos et al.

    Light visor treatment for jet lag after westaward travel across six time zones

    Aviat Space Environ Med

    (2002)
  • G. Brainard et al.

    Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor

    J Neurosci

    (2001)
  • H. Burgess et al.

    Individual differences in the amount and timing of salivary melatonin secretion

    PLoS ONE

    (2008)
  • L. Constandil et al.

    Day-night changes in c-fos expression in the fetal sheep suprachiasmatic nucleus at late gestation

    Reprod Fertil Dev

    (1995)
  • S. Coons et al.

    Development of consolidated sleep and wakeful periods in relation to the daynight cycle in infancy

    Dev Med Child Neurol

    (1984)
  • B. Corbett et al.

    Variable cortisol circadian rhythms in children with autism and anticipatory stress

    J Psychiatry Neurosci

    (2008)
  • J. Curin et al.

    Lower cortisol and higher ACTH levels in individuals with autism

    J Autism Dev Dis

    (2003)
  • L. Curzi-Dascalova et al.

    Neurophysiological basis and behavior of early sleep

  • C. Czeisler et al.

    Exposure to bright light and darkness to treat physiologic maladaptation to night work

    New Engl J Med

    (1990)
  • C. Czeisler et al.

    Stability, precision, and near-24-hour period of the human circadian pacemaker

    Science

    (1999)
  • G. Dawson et al.

    Children with autism fail to orient to naturally occurring social stimuli

    J Autsim Dev Dis

    (1998)
  • Cited by (129)

    • Sleep Problems and Circadian Functioning in Children and Adolescents With Autism Spectrum Disorder

      2022, Pediatric Neurology
      Citation Excerpt :

      Circadian rhythms can be studied using various indicators such as changes in different hormones, core body temperature, and rest-activity cycles.11-13 In individuals with ASD, melatonin has been found to be one of the most useful markers of the human circadian pacemaker, and previous research has reported dysregulated cortisol secretion in ASD compared with control subjects.10,14,15 Previous publications evaluating rest-activity cycles and sleep data in ASD have mainly used subjective data derived from questionnaires.

    View all citing articles on Scopus
    View full text