Elsevier

Pediatric Neurology

Volume 47, Issue 4, October 2012, Pages 242-251
Pediatric Neurology

Review Article
Sleep in Children With Autism Spectrum Disorder

https://doi.org/10.1016/j.pediatrneurol.2012.05.007Get rights and content

Abstract

Children with autism spectrum disorder demonstrate an increased prevalence of difficulties with sleep initiation and maintenance. The consequences may include alterations in daytime behavior, memory, and learning in patients, and significant stress in caretakers. The dysregulation of melatonin synthesis, sensitization to environmental stimuli, behavioral insomnia syndromes, delayed sleep phase syndrome, rapid eye movement sleep behavior disorder, and comorbid anxiety, depression, and epilepsy comprise common etiologic factors. The clinical assessment of sleep problems in this population and a management algorithm are presented.

Introduction

According to the Diagnostic and Statistical Manual IV, autism spectrum disorder is defined as a health condition with qualitative impairments in social interactions and communication in association with restricted, repetitive, and stereotyped behaviors, interests, and activities. The onset of the syndrome usually occurs before 3 years of age. The term encompasses autism, Asperger syndrome, and pervasive developmental disorder, not otherwise specified. In 2006, the Centers for Disease Control had estimated the incidence of autism spectrum disorder at 1 in 110 children, prevalence at 9 per 1000, and a male/female ratio of 4:1 [1]. It remains unclear whether an actual increase in occurrence of the disorder has taken place during the past decade, or whether more cases are being recognized as a consequence of increased awareness of autism spectrum disorder among the general population and health professionals. Perhaps both factors are in play. Regardless, health professionals who care for developmentally disabled children seem to be encountering larger numbers of patients with a diagnosis of autism spectrum disorder in their office practice. Given the pervasiveness of sleep problems in autism spectrum disorder, their potential for adverse effects upon both the patient and caretaker, and the likely availability of some treatments, we provide an overview of sleep-wake problems in this population.

Section snippets

Prevalence of sleep-wake problems

Parental surveys indicate a 50-80% prevalence of sleep problems in children with autism spectrum disorder, compared with a 9-50% prevalence rate in age-matched, typically developing subjects [2], [3], [4], [5], [6]. The degree of cognitive impairment likely does not influence the prevalence of sleep problems in autism spectrum disorder, because they are observed in those who are severely mentally handicapped as well as those who are high functioning, with intelligence quotients greater than 70

Relationship of sleep problems to specific clinical characteristics of autism spectrum disorder

In a survey of 250 Hong Kong Chinese children with pervasive developmental disorder, Doo and Wing, using the Children’s Sleep Habits Questionnaire, reported that the onset of pervasive developmental disorder signs before age 2 years was predictive of significant sleep problems [5]. Bedtime resistance and parasomnias comprised the most common types of sleep disturbance.

Based on their clinical course, children with autism spectrum disorder can be subdivided into those with indolent signs since

Role of good sleep in learning and behavioral regulation

Early developmental and behavioral intervention is the cornerstone of management in autism spectrum disorder [15]. To some extent, the success of early intervention hinges on sleep, which is essential for optimizing cognition, memory, behavioral regulation, and learning [16], [17], [18]. For an event to be encoded and then consolidated into long-term memory, exposure to adequate sleep is essential after occurrence of the event [16]. In this regard, procedural memories, such as those for

Developmental aspects of sleep dysregulation

In a small number of patients, autism has been associated with mutations in the neuroligin-3 (NLGN3) and neuroligin-4 (NLGN4) genes that are expressed at postsynaptic sites [22]. In conjunction with synaptic scaffolding protein 3 (SHANK3) and the presynaptically located neurexin (NRXN1) gene, neuroligin-3 and neuroligin-4 regulate the formation of synapses [22]. Neurexins and neuroligins influence the glutamine-related vs γ-amino butyric acid-related specialization of synapses. The insertion of

Neurophysiologic aspects of sleep dysregulation

Wrist actigraphy and nocturnal polysomnography comprise two tools commonly used in the study of sleep in autism spectrum disorder. Actigraphy uses an accelerometer to detect and record muscle activity. The sampling rate consists of several times per second. The device is generally worn on the left wrist. Based on the presence or absence of muscle activity, researchers can determine with a reasonable degree of reliability when children go to sleep and awaken. This information can be gathered

Circadian rhythm sleep disturbances

Circadian (from the Latin circa = around, and diem = day) rhythms are regulated at the level of the suprachiasmatic nucleus of the hypothalamus by at least 10 known genes. Rhythmic oscillations of cells of the suprachiasmatic nucleus regulate slave clocks in other regions of the brain and peripheral clocks in other organ systems through direct projections or humoral factors [34]. The suprachiasmatic nucleus, which contains receptors for melatonin, influences the behavior, physiology, and

Sleep history

How alert and refreshed a child feels in the morning upon awakening provides a useful indicator of the quality of night sleep. Researchers should ask about daytime inattentiveness, mood swings, napping, and medications that may affect alertness and sleep. Events and rituals that may be unduly activating and that occur during the 4-6 hours before bedtime should be documented. Does fluctuation occur in the sleeping environment or in bedtime routines from one night to the next? Children with

Management

Our algorithm (Fig 2) provides a scheme for management. Initially the researcher needs to target the most likely type of disturbance, realizing that there more than one category of signs may be present. A multidisciplinary team approach involves the pediatric developmental specialist, neurologist, pediatrician, sleep specialist, psychologist, social worker, nurses, school authorities, and not least, the parents. Key components of management will be discussed next.

Future directions

Prolonged wakefulness of more than 6 hours induces endoplasmic stress and the unfolded protein response in the murine cerebral cortex [55]. Concentrations of immunoglobulin-binding protein, also known as heat-shock protein 5A, rise within 6, 9, and 12 hours of sleep deprivation [56]. Similarly, the function of a variety of genes such as endoplasmic reticulum protein-72, the eukaryotic translation initiation factor eiF4B, and caspase-9, which are involved with the endoplasmic stress response, is

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