Cardiovascular regulation profile predicts developmental trajectory of BMI and pediatric obesity

The present study examined the role of cardiovascular regulation in predicting pediatric obesity. Participants for this study included 268 children (141 girls) obtained from a larger ongoing longitudinal study. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (vagal withdrawal) to three cognitively challenging tasks were derived when children were 5.5 years of age. Heart period (HP) and HP change (heart rate (HR) acceleration) were also examined. Height and weight measures were collected when children were 5.5, 7.5, and 10.5 years of age. Results indicated that physiological regulation at age 5.5 was predictive of both normal variations in BMI development and pediatric obesity at age 10.5. Specifically, children with a cardiovascular regulation profile characterized by lower levels of RSA suppression and HP change experienced significantly greater levels of BMI growth and were more likely to be classified as overweight/at-risk for overweight at age 10.5 compared to children with a cardiovascular regulation profile characterized by high levels of RSA suppression and HP change. However, a significant interaction with racial status was found suggesting that the association between cardiovascular regulation profile and BMI growth and pediatric obesity was only significant for African-American children. An autonomic cardiovascular regulation profile consisting of low parasympathetic activity represents a significant individual risk factor for the development of pediatric obesity, but only for African-American children. Mechanisms by which early physiological regulation difficulties may contribute to the development of pediatric obesity are discussed.     

Clinical Characteristics of Children with Autism Spectrum Disorder and Co-Occurring Epilepsy

Objectives

To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population.

Methods

Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy.

Results

The average prevalence of epilepsy in children with ASD 2–17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001).

Conclusion

This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy.     

孤独症谱系障碍儿童早期神经发育水平和智能特征分析

目的:探讨孤独症谱系障碍(Autism spectrum disorder,ASD)儿童早期神经发育水平及智能分区特征,为提高ASD的早期识别和诊断提供理论依据。方法:运用Gesell发育评估量表对18月龄至48月龄以内的27例ASD患儿和30例发育迟缓(Mental retardation, MR)患儿的发育商(Development quotient,DQ)进行测评,比较两组患儿的年龄、性别、平均DQ和各能区DQ。结果:两组患儿的年龄和性别未见明显差异(P>0.05),ASD患儿平均DQ落后于MR患儿(P<0.05),ASD患儿的语言和个人-社交明显落后于MR患儿(P<0.05),ASD患儿的语言和个人-社交明显落后于大运动、精细动作(P<0.05),语言明显落后于个人-社交和适应性(P<0.05),MR患儿的各能区未见明显差异(P>0.05)。结论:ASD患儿智能特征表现为整体发育水平落后且显著不平衡,以语言和个人-社交落后最明显。     

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder(ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment(SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.     

Autism and Sensory Processing Disorders: Shared White Matter Disruption in Sensory Pathways but Divergent Connectivity in Social-Emotional Pathways

Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment is now included in the DSM-5 diagnostic criteria. However, there are children with sensory processing differences who do not meet an ASD diagnosis but do show atypical sensory behaviors to the same or greater degree as ASD children. We previously demonstrated that children with Sensory Processing Disorders (SPD) have impaired white matter microstructure, and that this white matter microstructural pathology correlates with atypical sensory behavior. In this study, we use diffusion tensor imaging (DTI) fiber tractography to evaluate the structural connectivity of specific white matter tracts in boys with ASD (n = 15) and boys with SPD (n = 16), relative to typically developing children (n = 23). We define white matter tracts using probabilistic streamline tractography and assess the strength of tract connectivity using mean fractional anisotropy. Both the SPD and ASD cohorts demonstrate decreased connectivity relative to controls in parieto-occipital tracts involved in sensory perception and multisensory integration. However, the ASD group alone shows impaired connectivity, relative to controls, in temporal tracts thought to subserve social-emotional processing. In addition to these group difference analyses, we take a dimensional approach to assessing the relationship between white matter connectivity and participant function. These correlational analyses reveal significant associations of white matter connectivity with auditory processing, working memory, social skills, and inattention across our three study groups. These findings help elucidate the roles of specific neural circuits in neurodevelopmental disorders, and begin to explore the dimensional relationship between critical cognitive functions and structural connectivity across affected and unaffected children.     

Prospective MEG Biomarkers in ASD: Pre-Clinical Evidence and Clinical Promise of Electrophysiological Signatures

Autism spectrum disorders (ASD) are characterized by social impairments and restricted/stereotyped behaviors and currently affect an estimated 1 in 68 children aged 8 years old. While there has been substantial recent focus on ASD in research, both the biological pathology and, perhaps consequently, a fully effective treatment have yet to be realized. What has remained throughout is the hypothesis that ASD has neurobiological underpinnings and the observation that both the phenotypic expression and likely the underlying etiology is highly heterogeneous. Given the neurodevelopmental basis of ASD, a biologically based marker (biomarker) could prove useful not only for diagnostic and prognostic purposes, but also for stratification and response indices for pharmaceutical development. In this review, we examine the current state of the field for MEG-related biomarkers in ASD. We describe several potential biomarkers (middle latency delays [M50/M100], mismatch negativity latency, gamma-band oscillatory activity), and investigate their relation to symptomology, core domains of dysfunction (e.g., language impairment), and putative biological underpinnings.     

Intelligence May Moderate the Cognitive Profile of Patients with ASD

BackgroundThe intelligence of individuals with Autism Spectrum Disorder (ASD) varies considerably. The pattern of cognitive deficits associated with ASD may differ depending on intelligence. We aimed to study the absolute and relative severity of cognitive deficits in participants with ASD in relation to IQ.MethodsA total of 274 children (M age = 12.1, 68.6% boys) participated: 30 ASD and 22 controls in the below average Intelligence Quotient (IQ) group (IQ<85), 57 ASD and 54 controls in the average IQ group (85<IQ<115) and 41 ASD and 70 controls in the above average IQ group (IQ>115). Matching for age, sex, Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and VIQ-PIQ difference was performed. Speed and accuracy of social cognition, executive functioning, visual pattern recognition and basic processing speed were examined per domain and as a composite score.ResultsThe composite score revealed a trend significant IQ by ASD interaction (significant when excluding the average IQ group). In absolute terms, participants with below average IQs performed poorest (regardless of diagnosis). However, in relative terms, above average intelligent participants with ASD showed the most substantial cognitive problems (particularly for social cognition, visual pattern recognition and verbal working memory) since this group differed significantly from the IQ-matched control group (p < .001), whereas this was not the case for below-average intelligence participants with ASD (p = .57).ConclusionsIn relative terms, cognitive deficits appear somewhat more severe in individuals with ASD and above average IQs compared to the below average IQ patients with ASD. Even though high IQ ASD individuals enjoy a certain protection from their higher IQ, they clearly demonstrate cognitive impairments that may be targeted in clinical assessment and treatment. Conversely, even though in absolute terms ASD patients with below average IQs were clearly more impaired than ASD patients with average to above average IQs, the differences in cognitive functioning between participants with and without ASD on the lower end of the IQ spectrum were less pronounced. Clinically this may imply that cognitive assessment and training of cognitive skills in below average intelligent children with ASD may be a less fruitful endeavour. These findings tentatively suggest that intelligence may act as a moderator in the cognitive presentation of ASD, with qualitatively different cognitive processes affected in patients at the high and low end of the IQ spectrum.     

Cognitive abilities and language comprehension in preschool children with perinatal brain lesion

Perinatal brain lesion is a risk factor for development, making parents of such children particularly worried about consequences it may have on the child's cognitive and language development. Although literature findings on the outcome of perinatal brain lesion are inconsistent, most of the studies have found a positive general outcome, but also subtle deficits that affect the child's academic success. Since language comprehension and cognitive abilities influence learning abilities at school, we wanted to know how six-year olds who were selected based on pathological ultrasonographical findings (ischemic or hemorrhagic brain lesion) would perform on subtests of Wechsler battery (WISC) and language comprehension measures (Reynell Developmental Language Scale and Peabody Picture Vocabulary Test), compared with controls. The second issue we investigated was whether in children who suffered a perinatal brain lesion cognitive abilities predicted the level of language comprehension in the same way as in children without perinatal brain lesion. The relation between cognitive and linguistic abilities is still a controversial one, and a different relation would mean that these two groups of children have different structure of abilities probably due to perinatal brain lesion. Forty children who suffered a perinatal brain lesion and forty age-matched children without perinatal risk factors were examined. Our results showed that the groups differed more in linguistic than in cognitive variables. Also, the two groups showed different relation patterns between cognitive abilities and language comprehension. Cognitive abilities were statistically significantly associated with language comprehension in children who suffered a perinatal brain lesion, while this association was not statistically significant within the control group. Since a number of participants with perinatal brain lesion had language difficulties, it is presumed that they rely on cognitive abilities in order to overcome and compensate for language shortcomings.     

Sources of variation in developmental language disorders: evidence from eye-tracking studies of sentence production

Skilled sentence production involves distinct stages of message conceptualization (deciding what to talk about) and message formulation (deciding how to talk about it). Eye-movement paradigms provide a mechanism for observing how speakers accomplish these aspects of production in real time. These methods have recently been applied to children with autism spectrum disorder (ASD) and specific language impairment (LI) in an effort to reveal qualitative differences between groups in sentence production processes. Findings support a multiple-deficit account in which language production is influenced not only by lexical and syntactic constraints, but also by variation in attention control, inhibition and social competence. Thus, children with ASD are especially vulnerable to atypical patterns of visual inspection and verbal utterance. The potential to influence attentional focus and prime appropriate language structures are considered as a mechanism for facilitating language adaptation and learning.     

25OH维生素D水平检测与自闭症评定量表（CARS）评分的相关性及预测模型研究

摘要 目的：探究25OH维生素D（25(OH) D）水平检测与自闭症评定量表（CARS）评分的相关性及其评估自闭症严重程度的价值。方法：选取2020年4月~2022年3月在我院确诊的自闭症谱系障碍（ASD）患儿67例作为ASD组,并按照病情严重程度将所有患儿分为轻中度组46例,重度组36例。另募集来我科就诊无精神病史及家族史的健康查体儿童93例作为对照组。对比ASD组与对照组、ASD患儿轻中度组与重度组25(OH) D水平差异,分析ASD组患儿25(OH)D水平的影响因素,比较ASD组不同25(OH)D水平患儿CARS评分差异性,分析ASD患儿血清25(OH)D水平与CARS评分的相关性,并采用ROC曲线评估血清25(OH)D水平预估ASD严重程度的效能。结果：ASD组患儿血清25(OH) D水平显著低于于对照组（P<0.05）。相较于轻中度组,重度孤独症组患儿血清25(OH) D水平显著降低（P<0.05）。25(OH) D异常组患儿中母乳喂养、偏食及腹泻发生率显著高于25(OH) D正常组（P<0.05）。25(OH) D异常组患儿中CARS评分中的人际关系、模仿、情感反应、肢体动作、使用物体、对变化的适应、视觉反应、听觉反应及总分显著高于25(OH) D正常组（P<0.05）。CARS总分分与血清25(OH)D水平的成负相关性（r=-0.367,P=0.004）。血清25(OH)D水平预估ASD严重程度的AUC为0.716,敏感度为72.48%,特异度为78.65%。结论：血清25(OH)D在ASD患儿中成低表达,而且不同严重程度患儿血清25(OH)D差异表达,而且血清25(OH)D水平与CARS总分成负相关性,其作为评估ASD严重程度的生物标志物具有一定价值。     

Social cognition and underlying cognitive mechanisms in children with an extra X chromosome: a comparison with autism spectrum disorder

Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess theory of mind and facial affect labeling in children with an extra X chromosome. Forty‐six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with Trisomy X), 56 children with autism spectrum disorder (ASD) and 88 non‐clinical controls, aged 9–18 years, were included. Similar to children with ASD, children with an extra X chromosome showed significant impairments in social cognition. Regression analyses showed that different cognitive functions predicted social cognitive skills in the extra X and ASD groups. The social cognitive deficits were similar for boys and girls with an extra X chromosome, and not specific for a subgroup with high Autism Diagnostic Interview Revised autism scores. Thus, children with an extra X chromosome show social cognitive deficits, which may contribute to social dysfunction, not only in children showing a developmental pattern that is ‘typical’ for autism but also in those showing mild or late presenting autism symptoms. Our findings may also help explain variance in type of social deficit: children may show similar social difficulties, but these may arise as a consequence of different underlying information processing deficits.     

肠道微生物与自闭症谱系障碍

自闭症谱系障碍(autism spectrum disorder,ASD)是一种精神致残的重要疾病,严重影响儿童身心健康,给家庭和社会带来沉重的负担。患者常出现不同程度胃肠道症状和伴有肠道微生物组成的改变,以此为切入点,近年越来越多的研究聚焦于ASD和肠道微生物的关系上。本文介绍了肠道微生物组成、肠―脑轴及ASD患者肠道微生物的主要变化,并从多个方面阐述了ASD与肠道微生物的关系。     

White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study

Background

Autism spectrum disorders (ASD) are associated with widespread alterations in white matter (WM) integrity. However, while a growing body of studies is shedding light on microstructural WM alterations in high-functioning adolescents and adults with ASD, literature is still lacking in information about whole brain structural connectivity in children and low-functioning patients with ASD. This research aims to investigate WM connectivity in ASD children with and without mental retardation compared to typically developing controls (TD).

Methods

Diffusion tensor imaging (DTI) was performed in 22 young children with ASD (mean age: 5.54 years) and 10 controls (mean age: 5.25 years). Data were analysed both using the tract-based spatial statistics (TBSS) and the tractography. Correlations were investigated between the WM microstructure in the identified altered regions and the productive language level.

Results

The TBSS analysis revealed widespread increase of fractional anisotropy (FA) in major WM pathways. The tractographic approach showed an increased fiber length and FA in the cingulum and in the corpus callosum and an increased mean diffusivity in the indirect segments of the right arcuate and the left cingulum. Mean diffusivity was also correlated with expressive language functioning in the left indirect segments of the arcuate fasciculus.

Conclusions

Our study confirmed the presence of several structural connectivity abnormalities in young ASD children. In particular, the TBSS profile of increased FA that characterized the ASD patients extends to children a finding previously detected in ASD toddlers only. The WM integrity abnormalities detected may be relevant to the pathophysiology of ASD, since the structures involved participate in some core atypical characteristics of the disorder.

     

Investigating the Autonomic Nervous System Response to Anxiety in Children with Autism Spectrum Disorders

Assessment of anxiety symptoms in autism spectrum disorders (ASD) is a challenging task due to the symptom overlap between the two conditions as well as the difficulties in communication and awareness of emotions in ASD. This motivates the development of a physiological marker of anxiety in ASD that is independent of language and does not require observation of overt behaviour. In this study, we investigated the feasibility of using indicators of autonomic nervous system (ANS) activity for this purpose. Specially, the objectives of the study were to 1) examine whether or not anxiety causes significant measurable changes in indicators of ANS in an ASD population, and 2) characterize the pattern of these changes in ASD. We measured three physiological indicators of the autonomic nervous system response (heart rate, electrodermal activity, and skin temperature) during a baseline (movie watching) and anxiety condition (Stroop task) in a sample of typically developing children (n = 17) and children with ASD (n = 12). The anxiety condition caused significant changes in heart rate and electrodermal activity in both groups, however, a differential pattern of response was found between the two groups. In particular, the ASD group showed elevated heart rate during both baseline and anxiety conditions. Elevated and blunted phasic electrodermal activity were found in the ASD group during baseline and anxiety conditions, respectively. Finally, the ASD group did not show the typical decrease in skin temperature in response to anxiety. These results suggest that 1) signals of the autonomic nervous system may be used as indicators of anxiety in children with ASD, and 2) ASD may be associated with an atypical autonomic response to anxiety that is most consistent with sympathetic over-arousal and parasympathetic under-arousal.     

Behavioral,Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display “motor dyspraxia” or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism.     

Eye movement dynamics and cognitive self-organization in typical and atypical development

This study analyzed distributions of Euclidean displacements in gaze (i.e. “gaze steps”) to evaluate the degree of componential cognitive constraints on audio-visual speech perception tasks. Children performing these tasks exhibited distributions of gaze steps that were closest to power-law or lognormal distributions, suggesting a multiplicatively interactive, flexible, self-organizing cognitive system rather than a component-dominant stipulated cognitive structure. Younger children and children diagnosed with an autism spectrum disorder (ASD) exhibited distributions that were closer to power-law than lognormal, indicating a reduced degree of self-organized structure. The relative goodness of lognormal fit was also a significant predictor of ASD, suggesting that this type of analysis may point towards a promising diagnostic tool. These results lend further support to an interaction-dominant framework that casts cognitive processing and development in terms of self-organization instead of fixed components and show that these analytical methods are sensitive to important developmental and neuropsychological differences.     

慢性胃炎组织病理特征和Hp感染与炎症程度的关系研究

目的:探讨慢性胃炎组织病理特征和Hp感染与慢性炎症程度的关系。方法:抽选我院2010年1月至2016年2月行胃镜检查诊断为慢性胃炎的467例患儿,作胃窦黏膜病理组织学检查,并检测有无HP感染,分析HP感染与慢性胃炎病理特征、慢性炎症程度之间的关系。结果:在病理检查中,轻度、中度、重度炎症反应患儿HP感染率(7.7%、41.2%、51.1%)依次升高,且差异具有统计学意义(P0.05),有炎症活动度患儿的HP阳性率76.3%明显高于无炎症活动度患儿23.7%(P0.05)。随着肠化分级加重、淋巴滤泡形成、萎缩程度分级升高等病理变化,Hp阳性率明显升高(P0.05)。轻度、中度、重度炎症三组淋巴滤泡形成、肠化生和胃萎缩发生率明显呈递增趋势,Hp阳性率明显呈递增趋势,比较差异显著(P0.05)。结论:Hp是慢性胃炎发病的重要影响因素,与患儿胃窦黏膜炎症程度、活动性、淋巴滤泡形成、肠化分级以及黏膜萎缩萎等病理变化密切相关。     

The Physiological Role of Boron on Health

Environmental factors have been implicated in the etiology of autism spectrum disorder (ASD); however, the role of heavy metals has not been fully defined. This study investigated whether blood levels of mercury, arsenic, cadmium, and lead of children with ASD significantly differ from those of age- and sex-matched controls. One hundred eighty unrelated children with ASD and 184 healthy controls were recruited. Data showed that the children with ASD had significantly (p < 0.001) higher levels of mercury and arsenic and a lower level of cadmium. The levels of lead did not differ significantly between the groups. The results of this study are consistent with numerous previous studies, supporting an important role for heavy metal exposure, particularly mercury, in the etiology of ASD. It is desirable to continue future research into the relationship between ASD and heavy metal exposure.     

Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders

Autism spectrum disorders (ASD) are a group of related neurodevelopmental syndromes with complex genetic etiology. We identified a de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with cognitive and social delay. We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD; the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism; and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates. We comprehensively resequenced CNTNAP2 in 635 patients and 942 controls. Among patients, we identified a total of 27 nonsynonymous changes; 13 were rare and unique to patients and 8 of these were predicted to be deleterious by bioinformatic approaches and/or altered residues conserved across all species. One variant at a highly conserved position, I869T, was inherited by four affected children in three unrelated families, but was not found in 4010 control chromosomes (p = 0.014). Overall, this resequencing data demonstrated a modest nonsignificant increase in the burden of rare variants in cases versus controls. Nonetheless, when viewed in light of two independent studies published in this issue of AJHG showing a relationship between ASD and common CNTNAP2 alleles, the cytogenetic and mutation screening data suggest that rare variants may also contribute to the pathophysiology of ASD, but place limits on the magnitude of this contribution.