Sleep in children with autistic spectrum disorder

Children and adolescents with autistic spectrum disorders (ASD) suffer from sleep problems, particularly insomnia, at a higher rate than typically developing children, ranging from 40% to 80%. Sleep problems in ASD might occur as a result of complex interactions between biological, psychological, social/environmental, and family factors, including child rearing practices that are not conducive to good sleep. Interestingly, children with a history of developmental regression have a more disturbed sleep pattern than children without regression. Even though regulation of sleep in children with ASD is still poorly understood, circadian abnormalities in autism might be the result of genetic abnormalities related to melatonin synthesis and melatonin’s role in modulating synaptic transmission. Recently a bifurcation of the sleep/wake cycle with increased sensitivity to external noise and short sleep duration causing irregular sleep onset and wake up times has been suggested. Identifying and treating sleep disorders may result not only in improved sleep, but also impact favorably on daytime behavior and family functioning. Several studies have also demonstrated effectiveness of behavioral interventions for sleep onset and maintenance problems in these populations. When behavioral interventions are not effective or lead only to a partial response, pharmacological treatment options should be considered. Studies of melatonin use in children with ASD provide evidence for its effectiveness and safety in the long run. The clinician assessing a child with an ASD should screen carefully for sleep disorders and make referrals as indicated.     

Mercury exposure in children with autistic spectrum disorder: case-control study

Although mercury has been proven to be a neurotoxicant, there is a lack of data to evaluate the causal relationship between mercury and autism. We aim to see if there is increased mercury exposure in children with autistic spectrum disorder. We performed a cross-sectional cohort study over a 5-month period in 2000 to compare the hair and blood mercury levels of children with autistic spectrum disorder (n = 82; mean age 7.2 years) and a control group of normal children (n = 55; mean age 7.8 years). There was no difference in the mean mercury levels. The mean blood mercury levels of the autistic and control groups were 19.53 and 17.68 nmol/L, respectively (P = .15), and the mean hair mercury levels of the autistic and control groups were 2.26 and 2.07 ppm, respectively (P = .79). Thus, the results from our cohort study with similar environmental mercury exposure indicate that there is no causal relationship between mercury as an environmental neurotoxin and autism.     

Sleep in children with autistic spectrum disorder: A questionnaire and polysomnographic study

ObjectiveTo evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP).MethodsThirty-one patients with ASD (28 males, 3 females, aged 3.7–19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night.ResultsThe questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maintaining sleep, enuresis, repetitive behavior when falling asleep, and daytime sleepiness. Polysomnographically, ASD children showed reduced time in bed, total sleep time, sleep period time and rapid eye movement (REM) latency. ASD subjects had a CAP rate during slow-wave sleep (SWS) lower than normal controls, together with a lower percentage of A1 subtypes.ConclusionsASD children questionnaires showed a higher percentage of disorders of initiating and maintaining sleep than normal controls; this was not completely confirmed by sleep staging. CAP measures showed subtle alterations of NREM sleep which could be detected with an appropriate methodology of analysis. The reduction of A1 subtypes during SWS might play a role in the impairment of cognitive functioning in these subjects.     

Sleep in children with autistic spectrum disorder: a questionnaire and polysomnographic study

OBJECTIVE: To evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP). METHODS: Thirty-one patients with ASD (28 males, 3 females, aged 3.7-19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night. RESULTS: The questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maintaining sleep, enuresis, repetitive behavior when falling asleep, and daytime sleepiness. Polysomnographically, ASD children showed reduced time in bed, total sleep time, sleep period time and rapid eye movement (REM) latency. ASD subjects had a CAP rate during slow-wave sleep (SWS) lower than normal controls, together with a lower percentage of A1 subtypes. CONCLUSIONS: ASD children questionnaires showed a higher percentage of disorders of initiating and maintaining sleep than normal controls; this was not completely confirmed by sleep staging. CAP measures showed subtle alterations of NREM sleep which could be detected with an appropriate methodology of analysis. The reduction of A1 subtypes during SWS might play a role in the impairment of cognitive functioning in these subjects.     

Fragile X positivity in Chinese children with autistic spectrum disorder.

Chromosome analysis was performed in 105 Chinese children (96 boys, 9 girls) with autistic spectrum disorder to assess fragile X positivity. Seventy percent of these autistic children were mentally retarded. None of the children in the infantile autism group (N = 75) had fragile X positivity. Two boys in the autistic condition group (N = 30) had clinical features and chromosomal positivity for fragile X syndrome. The low (2%) prevalence rate of fragile X positivity in children with different degrees of expressivity of autistic features may be related to other factors rather than to pure autistic characteristics per se.     

Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder.

Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 2 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants. Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele and the other of the long allele. Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus. These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects. Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.     

Association of 5-HT2A receptor gene polymorphisms with gastrointestinal disorders in Egyptian children with autistic disorder

Gastrointestinal disturbances (GID) are frequently reported in children with autism spectrum disorders (ASD). Recently, mounting evidence suggests that there may be a genetic link for autism with gastrointestinal disturbances.We aimed to investigate whether there were any association between the -1438A/G, 102T/C and His452Tyr polymorphisms of the serotonin 2A receptor gene (5-HT2A) in Egyptian children with ASD and GID. Eighty children with autistic disorder and 100 healthy control children were examined. -1438A/G, 102T/C and His452Tyr polymorphisms of 5-HT2A were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant increase of the G allele and the GG genotype of the -1438A/G polymorphism was observed in children with autism than control, but there were no significant differences in the frequencies either of the 102T/C genotype or His452Tyr genotype between the two groups. There was a significant increase of homozygote A allele of the -1438A/G and CC genotype of the 102T/C polymorphism in ASD children with GID. This study supports the possible involvement of the 5-HT2A receptor in the development of ASD and associated GID.     

SLC25A12基因多态性与孤独性障碍的关联

目的：探讨SLC25A12基因单核苷酸多态性（SNP）与孤独性障碍的遗传关联性。方法：采用聚合酶链式反应和DNA芯片杂交技术,在124个汉族孤独性障碍患儿核心家系中,检测了SLC25A12基因的2个SNP位点（rs2056202,rs2292813）,采用传递不平衡检验（TDT）和单倍型的方法进行关联分析。结果：在124个患儿核心家系中,所测得的2个SNP位点的等位基因和基因型的频数分布均符合Hardy-Weinberg平衡检验（χ^2=0.009,P=0.92;χ^2=0.006,P=0.94）。而且这2个SNP处于一个强连锁不平衡区域（D’=0.842,r2=0.566）。对124个核心家系TDT检验,发现带有杂合子基因的父代优先传递给子代的等位基因的传递率和此传递率的置信区间差异无显著性（P〉0.05）;所有样本的2个SNP位点,未发现与孤独性障碍的显著关联。结论：SLC25A12基因可能不是这些汉族家庭儿童孤独性障碍的主要易感基因。     

Effectiveness of a novel community-based early intervention model for children with autistic spectrum disorder

The Nova Scotia early intensive behavior intervention model -NS EIBI ( Bryson et al., 2007 ) for children with autistic spectrum disorders was designed to be feasible and sustainable in community settings. It combines parent training and naturalistic one-to-one behavior intervention employing Pivotal Response Treatment - PRT (R. Koegel & Koegel, 2006 ). We followed 45 children (33 males, mean baseline age = 50 months) for 12months. Mean gains of 14.9 and 19.5 months were observed on expressive and receptive language measures, respectively, for children with an IQ of 50 or more at baseline versus 6.1 and 8.4 months for children with IQs less than 50. Behavior problems decreased significantly over the 1-year treatment for both groups, but autism symptoms decreased only for those with an IQ of 50 or more.     

Stability and change of IQ scores in preschool children diagnosed with autistic spectrum disorder

AIM: To investigate cognitive development in preschool-age children diagnosed with Autistic Spectrum Disorder (ASD; N = 39) compared with that of children diagnosed with mental retardation (MR; N = 14) and normally developing children (NC; N = 36). METHOD: In a prospective longitudinal study, cognitive development was tested at age 24 months (T1; SD = 6 months) and 43 months (T2; SD = 5). RESULTS: Group IQ scores were stable between T1 and T2 as evidenced by high correlations (r = .81, P < .01) and consistency of average group scores. At the same time however, about a third of children with ASD showed an increase of cognitive scores of 15 points or more. This increase of IQ was correlated with lower scores at the early screening of autistic traits (ESAT) at T1, higher IQ level at T2 and higher expressive language skills at T2. Intensity of treatment was not related to IQ increase. CONCLUSIONS: High correlations between cognitive scores in preschool children with ASD suggest that measurements of cognitive function are valid at this age. We found indications of both stability and change of IQ scores. Findings suggest that some children with ASD show catch-up intellectual development. To the best of our knowledge, this increase in IQ scores cannot be attributed to treatment effects.     

Relationship of autistic traits between parents and children with and without autism spectrum disorder

BackgroundAlthough parents with a child with autism spectrum disorder (ASD) have usually been identified as having the “broader autism phenotype”, empirical research on the differences in autistic-like characteristics between parents with and without ASD children has yielded inconsistent results.MethodThis survey of the autistic traits of parents and children was conducted in 119 parents with ASD children and 108 parents with typically developing (TD) children. Parents’ autistic traits were quantified using the Autism-Spectrum Quotient and children’s autistic traits were quantified using the Autism Spectrum Quotient—Children’s Version.ResultsThe autistic traits of ASD children were significantly higher than those of the TD children; however, autistic traits were similar between parents in the two groups. Furthermore, the correlations of autistic traits between parents and children were only significant for the TD group and not for the ASD group.ConclusionsThe current findings indicate that the relationship of autistic traits between parents and children exists in the TD group, and that the Autism-Spectrum Quotient may be used for parents as a screening aid to identify children who should be further screened for autistic traits.     

Investigation of VDR gene polymorphisms in twins with autism spectrum disorder

BackgroundTwin studies to clarify the etiology of autism, copy number variations (CNV), and genome-wide association studies (GWAS) have provided strong evidence that genetic factors play an important role in the etiology of Autism spectrum disorder (ASD). The purpose of this study is to determine the relationship between Vitamin D Receptor (VDR) gene polymorphisms and disease development in ASD twins.MethodThe study included 32 pairs of dizygotic twins (64 patients) with ASD and 100 healthy subjects as the control group. Genomic DNA was isolated from blood samples. It is performed by PCR designed with region-specific primers. After the PCR procedure, RFLP was performed with appropriate enzymes to determine genotypes. The results were statistically evaluated by Chi Square Test and Haplotype analysis.ResultsWhen the results of our study were examined, the frequency of the variant CC genotype of FokI (rs2228570 T/C), the frequency of the variant TT genotype of ApaI (rs7975253 G/T) and the frequency of the variant TT genotype of TaqI(rs731236 T/C) were significantly higher than the control group (p:0,019, p:0,039, p:0,037).ConclusionsIn this study, single nucleotide changes in three different variants of the VDR gene were investigated in dizygotic twins cases with ASD in Turkey. Genotypically, it was found that patients showed statistically significant difference in all three regions compared to controls. In terms of allele frequencies of SNPs, it was observed that ApaI and TaqI allele frequencies were statistically significantly different between dizygotic patients with ASD and healthy controls.     

Constructing fictional stories: A study of story narratives by children with autistic spectrum disorder

Children with autistic spectrum disorder (ASD) are reported to have difficulties with narrative language but little is known about how this affects their production of fictional stories. In this study, we aimed to establish whether fictional narratives of children with ASD differed from those of typically developing children and if performance was commensurate with levels of oral language. Fictional stories produced by 27 high functioning children with ASD, aged 11–14 yrs, were compared with those of language and age matched groups of typically developing children. Differences were found between the children with ASD and comparison groups in structural, evaluative and global features of their stories indicating specific difficulties with this form of narrative. Stories of the ASD group were shorter and contained fewer causal statements than those of both comparison groups and sentences were less grammatically complex than those of the age match but not the language match group. In global measures, the stories of the ASD group were impoverished relative to both comparison groups. The results are discussed in relation to cognitive theories of autism and language development.     

Language comprehension of children with Asperger's disorder and children with autistic disorder

This study investigated language comprehension of Mandarin-speaking children with Asperger's disorder (AspD) (n = 88) and children with autistic disorder (AD) (n = 136) and compared their language comprehension to that of children with typical development (TD) (n = 832). The Mandarin Token Test was used in this study. This study found that (a) when IQ was not controlled, children with AspD showed higher language comprehension than did children with AD. But, when IQ was controlled, there was no significant difference between the two groups; (b) children with AspD did not differ from children with TD in language comprehension; (c) gender difference was found in the AspD group at the middle childhood age level (10–12 years).     

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement

One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.     

Postoperative cerebellar mutism and autistic spectrum disorder

Purpose  

I read the article “An Inside View of Autism” written by a 44-year-old autistic woman who had a successful international career designing livestock equipment. In this article, she wrote about her life, disease, and experiences as an autistic individual. She stated that “It is interesting that my speech resembled the stressed speech in young children who have had tumors removed from the cerebellum”.     

The prevalence of autistic spectrum disorder in children surveyed in a tertiary care epilepsy clinic

It is well documented that children with autistic spectrum disorder (ASD) have an increased prevalence of seizures; however, studies have not been done to evaluate the prevalence of ASD in children with epilepsy. This comorbidity is important to define as early diagnosis and intervention in some children with ASD has been shown to improve outcome. METHOD: Children with epilepsy seen in a tertiary care epilepsy clinic were evaluated using validated autism screening questionnaires (ASQ). In addition, questions about sleep-related disorders, behavior, seizure characteristics, antiepileptic agents, and body mass index (BMI) were requested. An attempt was then made to determine if there was a correlation between the factors identified and ASD. RESULTS: Of the 107 questionnaires returned, 97 ASQ's were properly completed and used in this study. Approximately 32% of children fit the ASQ criteria for having ASD. Most children had not been previously diagnosed. Worst behavior and daytime sleepiness was seen in those at greater risk (p < 0.01). Seizures also occurred earlier (approximately 2 years) in children at risk of having ASD. CONCLUSION: Though confirmatory diagnostic evaluations are needed, this questionnaire-based study suggests that children with epilepsy are at greater risk of having ASD, and illustrates the need for more clinical vigilance. Behavioral difficulties and daytime sleepiness identified in these children could potentially affect their ability to learn. It is of interest that the age of seizure onset identified in those at greater risk corresponds with the approximate age of regression identified in some children with ASD.