Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients

Yang, Zhiliang; Matsumoto, Ayumi; Nakayama, Kazuhiro; Jimbo, Eriko F.; Kojima, Karin; Nagata, Koh‐ichi; Iwamoto, Sadahiko; Yamagata, Takanori

doi:10.1016/j.braindev.2015.04.006

Cited by 92 publications

(97 citation statements)

References 32 publications

(35 reference statements)

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“…Behavioral insomnias of childhood (BIC) are the most common extrinsic causes of insomnia in children, including those with ASD [26, 32–34]. However, the underlying biological and behavioral rhythms of ASD may predispose children to both extrinsic and intrinsic stressors that threaten sleep, making children with ASD uniquely vulnerable to sleep problems [11, 26, 31, 35]. Hypotheses regarding intrinsic causes of insomnia in children with ASD include (1) brain wave organizational and maturational differences, (2) circadian-relevant genes, (3) abnormal melatonin production, and (4) arousal and sensory dysregulation.…”

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

“…Another emerging hypothesis for intrinsic causes of insomnia in children with ASD includes circadian-relevant gene anomalies resulting in biological and behavioral rhythm disturbances [45, 46, 31, 11, 47, 48]. In humans, sleep and wakefulness are regulated in part by an endogenous circadian clock, the suprachiasmatic nucleus in the brain [11].…”

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

“…In humans, sleep and wakefulness are regulated in part by an endogenous circadian clock, the suprachiasmatic nucleus in the brain [11]. This master clock orchestrates a circadian rhythm system of positive and negative feedback loops that alter clock gene expression [11]. Clock genes PERIOD (PER 1, 2, 3 main framework), TIMELESS (resets clock), NPAS2, and Cryptocromes (CRY1,2) interact and are activated by clock proteins CLOCK, ARNTL/BMAL1 [49–52].…”

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

“…In addition, two clock gene variants, in PER1 and NPAS2, were found to be associated with a 110-member autism cohort from Autism Genetic Resources Exchange [54]. The coding regions of 18 canonical clock genes and clock controlled genes were sequenced in 28 participants with ASD, and PER2, PER 3, and TIMELESS variants were found to be associated with ASD [11]. However, the results from these studies were limited by small sample sizes and/or lack of significance after corrections for multiple analyses.…”

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

See 4 more Smart Citations

Sleep in Children with Autism Spectrum Disorder

Souders

Zavodny

Eriksen

et al. 2017

Curr Psychiatry Rep

200

143

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The purposes of this paper are to provide an overview of the state of the science of sleep in children with autism spectrum disorder (ASD), present hypotheses for the high prevalence of insomnia in children with ASD, and present a practice pathway for promoting optimal sleep. Approximately two thirds of children with ASD have chronic insomnia, and to date, the strongest evidence on promoting sleep is for sleep education, environmental changes, behavioral interventions, and exogenous melatonin. The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for screening, identification, and treatment for sleep problems in ASD in 2012. An exemplar case is presented to integrate key constructs of the practice pathway and address arousal and sensory dysregulation in a child with ASD and anxiety disorder. This paper concludes with next steps for dissemination of the practice pathway and future directions for research of sleep problems in ASD.

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Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

Section: What Are the Hypotheses For The High Prevalence Of Insomnia mentioning

confidence: 99%

See 3 more Smart Citations

Sleep in Children with Autism Spectrum Disorder

Souders

Zavodny

Eriksen

et al. 2017

Curr Psychiatry Rep

200

143

View full text Add to dashboard Cite

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Sleep phenotype of individuals with autism spectrum disorder bearing mutations in the PER2 circadian rhythm gene

Hoang

Yuen

Howe

et al. 2021

American J of Med Genetics Pt A

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The Per family of genes functions as a primary circadian rhythm maintenance in the brain. Mutations in PER2 are associated with familial advanced sleep‐phase syndrome 1 (FASPS1), and recently suggested in delayed sleep phase syndrome and idiopathic hypersomnia. The detection of PER2 variants in individuals with autism spectrum disorder (ASD) and without reported sleep disorders, has suggested a role of circadian‐relevant genes in the pathophysiology of ASD. It remains unclear whether these individuals may have, in addition to ASD, an undiagnosed circadian rhythm sleep disorder. The MSSNG database was used to screen whole genome sequencing data of 5,102 individuals with ASD for putative mutations in PER2. Families identified were invited to complete sleep phenotyping consisting of a structured interview and two standardized sleep questionnaires: the Pittsburgh Sleep Quality Index and the Morningness‐Eveningness Questionnaire. From 5,102 individuals with ASD, two nonsense, one frameshift, and one de novo missense PER2 variants were identified (0.08%). Of these four, none had a diagnosed sleep disorder. Three reported either a history of, or ongoing sleep disturbances, and one had symptoms highly suggestive of FASPS1 (as did a mutation carrier father without ASD). The individual with the missense variant did not report sleep concerns. The ASD and cognitive profiles of these individuals varied in severity and symptoms. The results support a possible role of PER2‐related circadian rhythm disturbances in the dysregulation of sleep overall and sometimes FASPS1. The relationship between dysregulated sleep and the pathophysiology of ASD require further exploration.

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The role of CLOCK gene in psychiatric disorders: Evidence from human and animal research

Schuch

Genro

Bastos

et al. 2017

American J of Med Genetics Pt B

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The circadian clock system drives daily rhythms in physiology, metabolism, and behavior in mammals. Molecular mechanisms of this system consist of multiple clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core member that plays an important role in a wide range of behaviors. Alterations in the CLOCK gene are associated with common psychiatric disorders as well as with circadian disturbances comorbidities. This review addresses animal, molecular, and genetic studies evaluating the role of the CLOCK gene on many psychiatric conditions, namely autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder. Many animal experiments focusing on the effects of the Clock gene in behavior related to psychiatric conditions have shown consistent biological plausibility and promising findings. In humans, genetic and gene expression studies regarding disorder susceptibility, sleep disturbances related comorbidities, and response to pharmacological treatment, in general, are in agreement with animal studies. However, the number of controversial results is high. Literature suggests that the CLOCK gene exerts important influence on these conditions, and influences the susceptibility to phenotypes of psychiatric disorders.

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Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients

Cited by 92 publications

References 32 publications

Sleep in Children with Autism Spectrum Disorder

Sleep in Children with Autism Spectrum Disorder

Sleep phenotype of individuals with autism spectrum disorder bearing mutations in the PER2 circadian rhythm gene

The role of CLOCK gene in psychiatric disorders: Evidence from human and animal research

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