Sleep in Children With Autism Spectrum Disorder

Kotagal, Suresh; Broomall, Eileen

doi:10.1016/j.pediatrneurol.2012.05.007

Cited by 211 publications

(124 citation statements)

References 58 publications

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Section: Introductionmentioning

confidence: 92%

“…2 Parents of children with ASD report 50-80% prevalence of sleep problems compared with a 9-50% prevalence rate reported by parents of age-matched typically developing children. 2 Common sleep etiological factors that are present in children with ASD are rapid eye movement sleep abnormalities, dysregulation of melatonin synthesis, difficulty in settling to sleep, night waking, irregular sleep patterns, short-duration sleep, and daytime sleepiness. 2,3 Persistent sleep problems are thought to adversely affect cognitive, physical, and social function, learning, mood, and behavior in these individuals and, in addition, cause significant stress for families and caretakers.…”

Section: Introductionmentioning

confidence: 92%

“…2 Common sleep etiological factors that are present in children with ASD are rapid eye movement sleep abnormalities, dysregulation of melatonin synthesis, difficulty in settling to sleep, night waking, irregular sleep patterns, short-duration sleep, and daytime sleepiness. 2,3 Persistent sleep problems are thought to adversely affect cognitive, physical, and social function, learning, mood, and behavior in these individuals and, in addition, cause significant stress for families and caretakers. 3 Better understanding of the sleep difficulties experienced by children with ASD may reduce the adverse effects and decrease family stress, possibly with targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

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MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith–Magenis and fragile X syndromes

et al. 2014

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Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/ snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders. Significant sleep problems are highly prevalent in individuals with ASD. 2 Parents of children with ASD report 50-80% prevalence of sleep problems compared with a 9-50% prevalence rate reported by parents of age-matched typically developing children. 2 Common sleep etiological factors that are present in children with ASD are rapid eye movement sleep abnormalities, dysregulation of melatonin synthesis, difficulty in settling to sleep, night waking, irregular sleep patterns, short-duration sleep, and daytime sleepiness. 2,3 Persistent sleep problems are thought to adversely affect cognitive, physical, and social function, learning, mood, and behavior in these individuals and, in addition, cause significant stress for families and caretakers. 3 Better understanding of the sleep difficulties experienced by children with ASD may reduce the adverse effects and decrease family stress, possibly with targeted therapies.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith–Magenis and fragile X syndromes

et al. 2014

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“…Rett's disorder, tuberous sclerosis, Smith–Magenis syndrome and Angelman syndrome) (Kotagal and Broomall, 2012; Elrod and Hood, 2015). The sleep disturbances exacerbate cognitive performance deficits and behavioural problems and subsequently entire family distress (Doo and Wing, 2006).…”

Section: Melatonin In the Treatment Of Circadian Rhythm And Sleep Dismentioning

confidence: 99%

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Zisapel

2018

British J Pharmacology

567

350

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In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN‐activated, light‐inhibited production of melatonin conveys the message of darkness to the clock and induces night‐state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo‐controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm‐related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non‐restorative) sleep quality, non‐dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep‐anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build‐up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease.Linked ArticlesThis article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

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“…Otherwise, melatonin receptor independent pathway is unaffected by morphophysiological barriers including the blood brain barrier [21,22]. In clinical, melatonin is commonly used for insomnia, and also applied in children with autism [23]. And experimental studies reported that melatonin treatment could attenuate sleep disorder without side effect [24].…”

Section: Introductionmentioning

confidence: 99%

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

Won

Jin

Lee

et al. 2017

Preprint

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Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

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Sleep in Children With Autism Spectrum Disorder

Cited by 211 publications

References 58 publications

MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith–Magenis and fragile X syndromes

MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith–Magenis and fragile X syndromes

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

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