Association of Duchenne muscular dystrophy with autism spectrum disorder

We hypothesize that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur with a greater than random frequency. In this study, we set out to reject the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur no more often than expected by chance. Two index cases and six additional boys with concomitant Duchenne muscular dystrophy and autism spectrum disorder were identified in a muscular dystrophy clinic that approximates the total number of Duchenne muscular dystrophy boys (158) in the state of Massachusetts. The rate of prevalence (6 of 158) was compared with the prevalence rate of autism spectrum disorder in boys in the general population (1.6 in 1,000). We rejected the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder co-occurrence was likely to be explained by chance (P = .006). We identify a previously unrecognized association of Duchenne muscular dystrophy with autism spectrum disorder. Further work might elucidate the level of association between these two conditions, either at the genetic or at the protein level, and might clarify, at least partially, the neurobiologic mechanisms associated with autism spectrum disorder.     

Mirroring effect in 2- and 3-year-olds with autism spectrum disorder

Previous studies have suggested that being imitated by an adult is an effective intervention with children with autism and developmental delay. The purpose of this study wais to investigate whether “mirroring” interaction, which includes being imitated by an adult, can facilitate the social responsiveness of toddlers with autism spectrum disorder (ASD). Participants were 16 toddlers (2- and 3-year-olds) with ASD. This study consisted of three experimental phases: in the first baseline phase, the experimenter manipulated toys in front of the participant; in the second phase, the experimenter reproduced (mirrored) all of the child's behaviors; and in the third phase, the first baseline phase was repeated. Our results demonstrated that although the mirroring effect differed by age, the effect was observed in both 2- and 3-year-olds with ASD. In addition, the overall magnitude of the mirroring effect differed by IQ, but not by the severity of autistic symptoms. Mirroring interaction is promising as an early intervention for a wide range of children with ASD.     

孤独谱系障碍2～3岁患儿杏仁核体积的研究

目的 分析2～3岁孤独谱系障碍(autism spectrum disorder,ASD)儿童与发育障碍儿童杏仁核体积的差异,并对ASD儿童杏仁核体积与社会情绪功能之间的相关性进行研究.方法 对46例ASD儿童(ASD组)和39例年龄、性别、发育商与之匹配的发育障碍儿童(对照组)进行磁共振扫描,手工勾画杏仁核,比较两组杏仁核体积的差异,利用婴幼儿沟通及象征性行为发展量表(Communication and Symbolic Behavior Scales Developmental Profile,CSBS-DP)评估患儿的社会交流能力,分析杏仁核体积与临床症状的相关性.结果 与对照组相比,2～3岁ASD儿童双侧杏仁核体积明显增大[左侧:(0.83 ±0.15) cm3与(0.72±0.13) cm3,t=3.55,P=0.001;右侧:(0.86±0.15)cm3与(0.77±0.12) cm3,t =2.83,P=0.006];在控制年龄和发育商后,ASD组儿童左侧杏仁核体积与社交领域中的手势项目(r=-0.331,P=0.042)及象征性行为领域中的游戏技巧项目均呈负相关(r=-0.333,P=0.041).结论 2～3岁的ASD儿童存在杏仁核体积增大,可能与患儿的社会情绪功能受损有关.     

Association between history of miscarriage and autism spectrum disorder

This case–control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327–3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259–3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939–4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153–4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978–3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534–4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252–2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894–4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus.

     

Genes associated with autism spectrum disorder

Autism spectrum disorder (ASD) is a heterogeneous grouping of neurodevelopmental disorders characterized by impairment in social interaction, verbal communication and repetitive/stereotypic behaviors. Much evidence suggests that ASD is multifactorial with a strong genetic basis, but the underlying mechanisms are far from clear. Recent advances in genetic technologies are beginning to shed light on possible etiologies of ASD. This review discusses current evidence for several widely studied candidate ASD genes, as well as various rare genes that supports their relationship to the etiology of ASD. The majority of the data are based on molecular, cytogenetic, linkage and association studies of autistic subjects, but newer methods, including whole-exome sequencing, are also beginning to make significant contributions to our understanding of autism.     

Sleep in children with autism spectrum disorder

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.     

Association of dopamine gene variants,emotion dysregulation and ADHD in autism spectrum disorder

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3′-UTR 9/10 VNTR, rs27072 in the 3′-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents’ ratings) was associated with DAT1 intron8 (ηp² = .063) and rs2283265 (ηp² = .044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (ηp² = .065) and depression (ηp² = .059), and for DRD2 rs2283265, depression (ηp² = .053). DRD2 rs2283265 was associated with teachers’ global ratings of ADHD (ηp² = .052). DAT1 intron8 was associated with parent-rated hyperactivity (ηp² = .045) and both DAT1 9/10 VNTR (ηp² = .105) and DRD2 rs2283265 (ηp² = .069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples.     

Association of DRD4 polymorphism with severity of oppositional defiant disorder,separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder

The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother‐ and teacher‐completed DSM‐IV‐referenced rating scale. Partial eta‐squared (ηp²) was used to gauge the magnitude of group differences: 0.01?0.06 = small, 0.06?0.14 = moderate and > 0.14 = large. Children who were 7‐repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers’ (ηp² = 0.10) and teachers’ (ηp² = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7‐repeat allele carriers also obtained more severe maternal ratings of tics (ηp² = 0.07) and obsessions–compulsions (ηp² = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, ηp² = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers’ ratings of oppositional behavior and mothers’ ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples.     

孤独谱系障碍患儿的感觉特征

目的 使用中文版儿童感觉剖析量表探讨孤独谱系障碍(ASD)患儿的感觉特点.方法 采用中文版儿童感觉剖析量表对66例ASD患儿和66名健康发育儿童进行评定,由监护人完成.分析孤独症患儿与健康儿童在感觉方面的差异.结果 除感觉剖析量表的口腔感觉处理和影响活动水平的运动的调节部分外,ASD患儿在其他部分及全量表的得分均与健康儿童的差异有统计学意义(P<0.01).结论 除口腔感觉处理和影响活动水平的运动的调节外,ASD患儿的各项感觉特征与健康发育儿童均存在一定差异.中文版儿童感觉剖析量表对区别ASD患儿与健康发育儿童有一定的鉴别力.     

Patterns of autism spectrum symptomatology in individuals with Down syndrome without comorbid autism spectrum disorder

Background

Prevalence estimates of autism spectrum disorder (ASD) in Down syndrome (DS) are highly varied. This variation is partly due to the difficulty of screening for and diagnosing comorbid ASD in individuals with a syndrome that carries its own set of social communicative and behavioral difficulties that are not well documented. The aim of this study was to identify the typical range of social communicative impairments observed in children, adolescents, and young adults with DS who do not have comorbid ASD.

Methods

We examined patterns of scores from the five subscales of the Social Responsiveness Scale (SRS) in 46 individuals with DS (ages 10–21 years) without comorbid ASD relative to the published normative sample. We also explored the correlations between SRS symptomatology and age, nonverbal cognition, and receptive language.

Results

SRS scores were elevated (i.e., more ASD symptoms endorsed), with mean scores falling into the clinically significant range. Analysis by subscale revealed a specific pattern, with Autistic Mannerisms and Social Cognition scores significantly more elevated than Social Communication scores, which were significantly more elevated than Social Awareness and Social Motivation scores. Correlations between SRS scores and the other measures varied by subscale.

Conclusions

General elevated ASD symptomatology on the SRS indicates the need for developing population-based norms specific to DS. The pattern of scores across subscales should inform clinicians of the typical range of behaviors observed in DS so that individuals with atypical patterns of behavior can be more easily identified and considered for a full ASD evaluation.     

Association of GABRB3 polymorphisms with autism spectrum disorders in Korean trios

BACKGROUND/AIMS: Autism spectrum disorders (ASD) are complex neuropsychiatric disorders having a genetic risk factor. The association and linkage study for the gamma-aminobutyric acid type A receptor beta3 subunit gene (GABRB3), located within the chromosome 15q11-q13 autism candidate region, and ASD have been evaluated. The aim of this study was to investigate the association between GABRB3 and ASD in the Korean population. METHODS: The present study was conducted with the detection of four single-nucleotide polymorphisms (rs1426217, rs2081648, rs890317, rs981778) in GABRB3 and association analysis in 104 Korean ASD trios using the transmission disequilibrium test. RESULTS: The transmission disequilibrium test demonstrated that an allele at rs2081648 showed preferential transmission (p = 0.027). One haplotype, including all examined markers in GABRB3, demonstrated significant association (p = 0.043), but the global chi2 test for haplotype transmission did not reveal an association between GABRB3 and ASD (chi2 = 15.516, d.f. = 15). CONCLUSION: Our finding suggested that single-nucleotide polymorphisms in GABRB3 may play a significant role in the genetic predisposition to ASD in the Korean population.     

Speech intonation in children with autism spectrum disorder

Objective: The prosody of children with autism spectrum disorder (ASD) has several abnormal features. We assessed the speech tone of children with ASD and of children with typical development (TD) by using a new quantitative acoustic analysis. Methods: Our study participants consisted of 63 children (26 with ASD and 37 with TD). The participants were divided into 4 groups based on their developmental features and age. We assessed the variety of the fundamental frequency (F0) pattern quantitatively, using pitch coefficient of variation (CV), considering the different F0 mean for each word. Results: (1) No significant difference was observed between the ASD and TD group at pre-school age. However, the TD group exhibited significantly greater pitch CV than the ASD group at school age. (2) In pitch CV, range and standard deviation of the whole speech of each participant, no significant differences were observed between the type of participants and age. (3) No significant correlation was found between the pitch CV of each word and the Japanese Autism Screening Questionnaire total score, or between the pitch CV of each word and the intelligence quotient levels in the ASD group. A significant correlation was observed between the pitch CV of each word and social reciprocal interaction score. Conclusions: We assessed the speech tone of children with ASD by using a new quantitative method. Monotonous speech in school-aged children with ASD was detected. The extent of monotonous speech was related to the extent of social reciprocal interaction in children with ASD.     

Molecular genetics of autism spectrum disorder

We are on the brink of exciting discoveries into the molecular genetic underpinnings of autism spectrum disorder. Overwhelming evidence of genetic involvement coupled with increased societal attention to the disorder has drawn in more researchers and more research funding. Autism is a strongly genetic yet strikingly complex disorder, in which evidence from different cases supports chromosomal disorders, rare single gene mutations, and multiplicative effects of common gene variants. With more and more interesting yet sometimes divergent findings emerging every year, it is tempting to view these initial molecular studies as so much noise, but the data have also started to coalesce in certain areas. In particular, recent studies in families with autism spectrum disorder have identified uncommon occurrences of a novel genetic syndrome caused by disruptions of the NLGN4 gene on chromosome Xp22. Previous work had identified another uncommon syndrome that is caused by maternal duplications of the chromosome 15q11-13 region. We highlight other converging findings, point toward those areas most likely to yield results, and emphasize the contributions of multiple approaches to identifying the genes of interest.     

1-磷酸鞘氨醇与孤独症谱系障碍相关临床表型的关联性

孤独症谱系障碍(autistic spectrum disorder,ASD)是一组神经发育障碍性疾病,目前病因尚不明确,其核心症状为社交障碍、重复行为和兴趣受限,其他症状包括认知障碍、感知觉障碍、焦虑抑郁等.1-磷酸鞘氨醇是神经酰胺的降解产物,在脑组织中含量丰富,在脑发育及调节神经元增殖、分化、存活和凋亡方面发挥重要...     

Magnetoencephalography in the study of children with autism spectrum disorder

Magnetoencephalography (MEG) is a non‐invasive neuroimaging technique that provides a measure of cortical neural activity on a millisecond timescale with high spatial resolution. MEG has been clinically applied to various neurological diseases, including epilepsy and cognitive dysfunction. In the past decade, MEG has also emerged as an important investigatory tool in neurodevelopmental studies. It is therefore an opportune time to review how MEG is able to contribute to the study of atypical brain development. We limit this review to autism spectrum disorder (ASD). The relevant published work for children was accessed using PubMed on 5 January 2015. Case reports, case series, and papers on epilepsy were excluded. Owing to their accurate separation of brain activity in the right and left hemispheres and the higher accuracy of source localization, MEG studies have added new information related to auditory‐evoked brain responses to findings from previous electroencephalography studies of children with ASD. In addition, evidence of atypical brain connectivity in children with ASD has accumulated over the past decade. MEG is well suited for the study of neural activity with high time resolution even in young children. Although further studies are still necessary, the detailed findings provided by neuroimaging methods may aid clinical diagnosis and even contribute to the refinement of diagnostic categories for neurodevelopmental disorders in the future.     

Association of schizophrenia spectrum and autism spectrum disorder (ASD) symptoms in children with ASD and clinic controls

ObjectiveThis study examines relations between the severity of specific symptoms of schizophrenia spectrum disorder (SSD) and severity of the three defining symptom domains of autism spectrum disorder (ASD) in children with ASD (N = 147) and child psychiatry outpatient referrals (Controls; N = 339).MethodParticipants were subdivided into four groups depending on ASD status (±) and whether they met symptom criteria for attention-deficit/hyperactivity disorder (±ADHD). Their mothers and teachers evaluated them with a DSM-IV-referenced rating scale.ResultsCorrelations between schizoid personality symptoms and ASD social skills deficits were moderate to large, and this was true for children with ASD and Controls, regardless of ADHD status, and for mother's and teachers’ ratings. Conversely, severity of hallucinations, delusions, and disorganized thinking were minimally correlated with ASD severity with the exception of Controls with ADHD. The disorganized behavior and negative symptoms of schizophrenia evidenced the strongest pattern of associations with ASD symptoms, and this was particularly true for children with co-morbid ADHD (±ASD, all three ASD symptom dimensions), and for teachers’ ratings of all four groups. Nevertheless, there was considerable variability in relations for specific symptoms across informants and groups. Correlations between SSD symptom severity and IQ were generally low, particularly among the ASD Only group and for all teacher-rated symptoms.ConclusionAssociations between ASD and SSD symptoms were often dimension-specific, and this was particularly evident in children without ADHD (±ASD; mothers’ ratings). Findings were interpreted as supporting the deconstruction of complex clinical phenotypes as a means of better understanding interrelations among psychiatric syndromes.     

Anthropometric measures of Spanish children with autism spectrum disorder

We aimed to compare body mass index (BMI) and healthy eating index (HEI) in children with autism spectrum disorder (ASD, n = 105) and typically developing (TD, n = 495) children. They were aged 6–9 years, lived in Valencia (Spain) and came from similar cultural and socio-economic backgrounds. In this case–control study, the weight, height and BMI were measured for both groups. Three-day food records were used to assess dietary intake. Although the differences between children with ASD and TD children in raw BMI (p = 0.44), BMI z-score (p = 0.37), HEI (p = 0.43) and total energy intake (p = 0.86) were not significant, children with ASD and the boys subgroup were shorter (p = 0.01), but not the girls subgroup, compared to TD children of the same gender. Using the controls values as a reference, the BMI distribution in children with ASD became distorted, with values below the 5th percentile (11% vs. 4%, p = 0.03) and above the 95th percentile (8% vs. 5%, p = 0.04). The gender- and age-adjusted odds ratios for being underweight in the groups of all children and boys with ASD were 3.03 and 2.39, respectively, vs. TD children. Our data suggest that routine monitoring of children with ASD should include anthropometric measurements and assessment of their dietary habits.