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.     

Genetics of Callous-Unemotional Behavior in Children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU.     

学龄前儿童细菌性腹泻的病原学特征及PCT、CD64和sTREM-1测定的临床意义

目的:分析学龄前儿童细菌性腹泻的病原学特征及血清中降钙素原(PCT)、中性粒细胞分化群64(CD64)和髓样细胞触发受体-1(s TREM-1)检测的临床意义。方法:选择2017年1月～2018年3月南方医科大学附属东莞市人民医院收治的214例学龄前感染性腹泻患儿为研究对象,包括细菌性腹泻(细菌组,n=101)和病毒性腹泻(病毒组,n=113),以同期入院行儿童保健的113例健康学龄前儿童为对照组。统计细菌组患儿的病原菌种类,比较两组腹泻患儿与对照组儿童血清PCT、CD64和s TREM-1水平的差异、三种血清学指标的阳性率及三种指标对细菌性腹泻患儿的诊断效能。结果:101例细菌性腹泻患儿粪便培养的细菌菌株中,共培养菌株213株,大肠埃希菌、志贺菌属和沙门菌属阳性率最高,分别占41.78%、23.01%和15.96%;细菌组的血清PCT、CD64和s TREM-1水平及阳性率均高于病毒组和对照组,且病毒组的s TREM-1水平高于对照组(P0.05);三种指标的灵敏度、特异度、阳性预测值和阴性预测值比较,差异无统计学意义(P0.05)。结论:学龄前儿童细菌性腹泻的致病菌主要为革兰阴性菌,PCT、CD64和s TREM-1均可作为判断细菌性腹泻的早期敏感指标。     

An Exploration of the Serotonin System in Antisocial Boys with High Levels of Callous-Unemotional Traits

Background

The serotonin system is thought to play a role in the aetiology of antisocial and aggressive behaviour in both adults and children however previous findings have been inconsistent. Recently, research has suggested that the function of the serotonin system may be specifically altered in a sub-set of antisocial populations – those with psychopathic (callous-unemotional) personality traits. We explored the relationships between callous-unemotional traits and functional polymorphisms of selected serotonin-system genes, and tested the association between callous-unemotional traits and serum serotonin levels independently of antisocial and aggressive behaviour.

Method

Participants were boys with antisocial behaviour problems aged 3–16 years referred to University of New South Wales Child Behaviour Research Clinics. Participants volunteered either a blood or saliva sample from which levels of serum serotonin (N = 66) and/or serotonin-system single nucleotide polymorphisms (N = 157) were assayed.

Results

Functional single nucleotide polymorphisms from the serotonin 1b receptor gene (HTR1B) and 2a receptor gene (HTR2A) were found to be associated with callous-unemotional traits. Serum serotonin level was a significant predictor of callous-unemotional traits; levels were significantly lower in boys with high callous-unemotional traits than in boys with low callous-unemotional traits.

Conclusion

Results provide support to the emerging literature that argues for a genetically-driven system-wide alteration in serotonin function in the aetiology of callous-unemotional traits. The findings should be interpreted as preliminary and future research that aims to replicate and further investigate these results is required.     

Bipolar Disorder with Seasonal Pattern: Clinical Characteristics and Gender Influences

Bipolar disorder (BD) has a multifactorial etiology with heterogeneous clinical presentations. Around 25% of BD patients may present with a depressive seasonal pattern (SP). However, there are limited scientific data on the prevalence of SP, its clinical manifestations, and any gender influence. Four hundred and fifty-two BD I and II cases (62% female), recruited from three French university-affiliated psychiatric departments, were assessed for SP. Clinical, treatment, and sociodemographic variables were obtained from structured interviews. One hundred and two (23%) cases met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for SP, with similar frequency according to gender. Multivariate analysis showed a significant association between SP and BD II (odds ratio [OR]?=?1.99, p?=?0.01), lifetime history of rapid cycling (OR?=?2.05, p?=?0.02), eating disorders (OR?=?2.94, p?=?0.003), and total number of depressive episodes (OR?=?1.13, p?=?0.002). Seventy-one percent of cases were correctly classified by this analysis. However, when stratifying the analyses by gender, SP was associated with BD II subtype (OR?=?2.89, p?=?0.017) and total number of depressive episodes (OR?=?1.21, p?=?0.0018) in males but with rapid cycling (OR?=?3.02, p?=?0.0027) and eating disorders (OR?=?2.60, p?=?0.016) in females. This is the first study to identify different associations between SP and clinical characteristics of BD according to gender. The authors suggest that SP represents a potentially important specifier of BD. These findings indicate that seasonality may reflect increased severity or complexity of disorder.     

Influence of the Personality Traits of Parent and Children on the Autonomic Regulation of Heart Rate in Children of Preschool Age and Adolescents

The relationship between personality traits and autonomic regulation of heart rate in children of preschool age and adolescents was studied. Significant positive correlations of the parameter of trait anxiety in children of preschool age with the index of tension (IT) of the cardiovascular system and of the value of extro/introversion of parents (mothers) with the IT of children were obtained. A relationship was revealed between school anxiety and the state of autonomic regulation of the heart rate in children of preschool age and adolescents.     

Characteristics of Cardiointerval Fluctuations in Preschool Age Children at Various Functional States

The dynamics of psychophysiological characteristics, the functional state (FS), the galvanic skin response (GSR), and stochastic parameters of the cardiac rhythm were studied in a group of children of preschool age. Two variants of the directional associative experiment (AE) were used: the simple AE and the AE with additional motivation (award for successful solution of the AE test). The mean RR interval value averaged over the group and the standard deviation of the RR interval fluctuations were found to be virtually insensitive to the FS changes in the experiment, whereas the dynamics of the GSR and the fractal index (exponent of the power function intended to approximate the spectral density ratio in the power spectrum of RR fluctuations) significantly depend on the FS variation. Age-related and standard characteristics of ECGs of preschool age children are discussed in the context of the body's life-support system and intense intellectual activity.     

学龄前阻塞性睡眠呼吸暂停低通气综合征儿童肠道菌群特征分析

摘要 目的：探讨学龄前阻塞性睡眠呼吸暂停低通气综合征（OSAHS）儿童与正常儿童肠道菌群的差异。方法：选取2023年7月至2023年11月期间新疆医科大学第一附属医院儿科门诊收治的学龄前OSAHS儿童30例作为OSAHS组,选取同期于新疆医科大学第一附属医院健康管理中心体检健康的儿童30例作为对照组。利用16SrDNA扩增子测序技术对肠道菌群进行分析。采用Spearman法分析睡眠质量与肠道菌群门、属水平丰度的相关性。结果：OSAHS组和对照组共发现2588个扩增子序列变异（ASVs）,OSAHS组检出特有ASVs 1034个,对照组检出特有ASVs 1554个。OSAHS组Chao1指数和Observed otus指数显著低于对照组（P<0.05）,两组间Shannnon指数、Simpson指数、Goods coverage指数、Peilou-e指数均差异无统计学意义（P>0.05）。OSAHS组与对照组间肠道菌群群落结构存在显著差异（P<0.05）。在门水平上,OSAHS组拟杆菌门的相对丰度低于对照组,厚壁菌门的相对丰度、厚壁菌门/拟杆菌门的比例高于对照组（P<0.05）。在属水平上,OSAHS组与对照组组优势菌群相对分度比较差异无统计学意义（P>0.05）。在门水平上,睡眠质量与拟杆菌门呈正相关（P<0.05）。在属水平上,睡眠质量与双歧杆菌属、乳杆菌属呈负相关,与拟杆菌属呈正相关（P<0.05）。阻塞性呼吸暂停低通气指数（OAHI）与肠杆菌属呈负相关（P<0.05）。最低血氧饱和度（LSaO₂）与肠杆菌属呈正相关（P<0.05）。平均血氧饱和度（MSaO₂）与X.Eubacterium._eligens_group呈正相关（P＜0.05）。结论：与正常儿童的肠道菌群的种类和相对丰度相比,学龄前OSAHS儿童的厚壁菌门/拟杆菌门比例升高,可能存在肠道菌群失调。睡眠质量在门、属水平上与拟杆菌门、双歧杆菌属、乳杆菌属明显相关。     

Examining the Genetic and Environmental Associations between Autistic Social and Communication Deficits and Psychopathic Callous-Unemotional Traits

Background

Difficulties in appropriate social interaction are characteristic of both children with autism spectrum disorders and children with callous-unemotional traits (who are at risk of developing psychopathy). Extant experimental studies suggest that the nature of atypical social cognition that characterises these two profiles is not identical. However, ‘empathizing’ difficulties have been hypothesised for both groups, raising questions about the degree of aetiological separation between social impairments that characterize each disorder. This study explored the relative contribution of independent vs. shared aetiological influences to social and communication impairments associated with autistic traits and callous-unemotional traits, indexed by parent-report in a population-based cohort of twins.

Methods

Participants were over 5,000 twin pairs from a UK cohort (the Twins Early Development Study; TEDS), assessed for callous-unemotional traits at 7 years and autistic social and communication impairments at 8 years. Multivariate model-fitting was used to explore the relative contribution of independent vs. overlapping genetic/environmental influences on these traits.

Results

Both social and communication impairments and callous-unemotional traits were highly heritable, although the genetic and environmental influences accounting for individual differences on each domain were predominantly independent.

Conclusions

Extant evidence from experimental and neuro-imaging studies has suggested that, despite some superficially overlapping behaviours, the social difficulties seen in children with autism spectrum disorders and callous-unemotional traits are largely distinct. The current study is the first to demonstrate considerable aetiological independence of the social interaction difficulties seen in children with autism spectrum disorders and those with callous-unemotional traits.     

儿童重症腺病毒肺炎的临床研究

目的:分析儿童重症腺病毒肺炎(SAP)的临床特点。方法:选择2011年01月至2015年01月广州市妇女儿童医疗中心重症监护室收治的被诊断为SAP的患儿53例。患儿入监护室后24 h内采集静脉血,检测血常规、血气、生化等指标,并结合病史与常规生化等检测指标同步给出PCIS评分。根据患儿的转归,将所有患儿分为生存组和死亡组进行比较分析。结果:53例重症腺病毒肺炎患儿,男女比例为3.4:1,2岁以下发病者48例,夏秋季发病共40例。死亡组患儿共8例(15.1%),其LDH、AST、Pa CO2水平、肺叶受累数量、并发症种类较存活组患儿明显升高,危重症评分(PCIS)、血小板、白蛋白、Pa O2水平、Pa O2/FIO2比值均较生存组显著降低(P均0.05)。结论:儿童SAP炎症反应重,常伴肺内外各种损害,早期的LDH、AST、白蛋白水平、血小板数量、Pa O2、Pa CO2、Pa O2/Fi O2及PCIS评分是疾病预后的早期预测指标,有助于临床医生对重症腺病毒肺炎患儿病情危重程度尽早作出正确判断。     

MRI Findings in 77 Children with Non-Syndromic Autistic Disorder

Background

The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000 [1]. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences.

Methodology

MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4±3.6) was performed. All met the DSM-IV and ADI –R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0±4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable.

Principal Findings

MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow–Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients).

Conclusions

An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism.     

Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are now recognized as a core symptom in autism spectrum disorder (ASD). Our ability to perceive and interact with the external world is rooted in sensory processing. For example, listening to a conversation entails processing the auditory cues coming from the speaker (speech content, prosody, syntax) as well as the associated visual information (facial expressions, gestures). Collectively, the “integration” of these multisensory (i.e., combined audiovisual) pieces of information results in better comprehension. Such multisensory integration has been shown to be strongly dependent upon the temporal relationship of the paired stimuli. Thus, stimuli that occur in close temporal proximity are highly likely to result in behavioral and perceptual benefits – gains believed to be reflective of the perceptual system''s judgment of the likelihood that these two stimuli came from the same source. Changes in this temporal integration are expected to strongly alter perceptual processes, and are likely to diminish the ability to accurately perceive and interact with our world. Here, a battery of tasks designed to characterize various aspects of sensory and multisensory temporal processing in children with ASD is described. In addition to its utility in autism, this battery has great potential for characterizing changes in sensory function in other clinical populations, as well as being used to examine changes in these processes across the lifespan.     

Social and Individual Components of Animal Contact in Preschool Children

ABSTRACT

Humans are generally biophilic. Still, for unknown reasons, interest in animals varies substantially among individuals. Our goal was to investigate how differential interest of children towards animals might be related to social competence and personality. We proposed two alternatives: 1) Children may compensate for potential deficits in social competence by resorting to animals, and 2) Socially well-connected children may show a particular interest in animals. We focused on relationships between age, gender, family background, play behavior, personality components, and contact with rabbits in 50 children (22 boys/28 girls; 3 to 7 years of age) at a preschool in Krems/Austria. Data were analyzed using GLM. We found that each one of these variables had significant impact on intensity of engagement with the rabbits. In general, girls, children with siblings, and children without pets were more oriented towards the rabbits than were boys, children without siblings, or pet-owning children. The older the children, the less frequently they occupied themselves with the rabbits but the longer they remained when they did engage them. Furthermore, we found that the more “Confident/Respected” (PCA factor 1) and less “Patient/Calm,” “Cheerful/Sociable,” and “Solitary” (PCA factors 2–4) the children, the more time they spent in direct occupation with rabbits. Most effects of the investigated variables varied between boys and girls. By and large, our findings support the hypothesis that the “socially competent” children were particularly interested in the animals. Also, children's social styles, as evinced in interactions with peers, were generally reflected in how they interacted with the rabbits.     

A Genetic Deconstruction of Neurocognitive Traits in Schizophrenia and Bipolar Disorder

Background

Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.

Methods

Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium.

Results

The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope.

Conclusions

Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.     

Morphofunctional Maturation of Preschool Children during Early Systematic Education

Experimental physiological, psychological, and hygienic longitudinal studies were carried out with children who began systematic developing education in the first childhood period (from 4 years) at preschool educational institutions. The results enabled the authors to evaluate the course of biological development at the fifth and sixth years of life. A two-year period at a preschool gymnasium or a kindergarten (teaching and upbringing complex) did not have a negative impact on the development of the children or their health. Developing lessons with their intellectual and static loads caused a notable fatigue in the children. The most manifest functional tension was found in the children with some developmental lag, mainly boys, whose development is delayed as compared to girls.     

Attention-Related Eye Vergence Measured in Children with Attention Deficit Hyperactivity Disorder

Recent evidence shows a novel role for eye vergence in orienting attention in adult subjects. Here we investigated whether such modulation in eye vergence by attention is present in children and whether it is altered in children with ADHD compared to control subjects. We therefore measured the angle of eye vergence in children previously diagnosed with ADHD while performing a cue task and compared the results to those from age-matched controls. We observed a strong modulation in the angle of vergence in the control group and a weak modulation in the ADHD group. In addition, in the control group the modulation in eye vergence was different between the informative cue and uninformative cue condition. This difference was less noticeable in the ADHD group. Our study supports the observation of deficient binocular vision in ADHD children. We argue that the observed disruption in vergence modulation in ADHD children is manifest of altered cognitive processing of sensory information. Our work may provide new insights into attention disorders, like ADHD.     

The Development of Elementary Forms of Thinking in Preschool Children

Among the new problems that society has posed to the educational system, that of developing preschool children's intellectual ability is of special importance. One of the central questions of intellectual training is developing children's thinking.     

Neurophysiological Determinants of Tic Severity in Children with Chronic Motor Tic Disorder

Tics wax and wane in severity. Although the understanding of the natural course of symptoms in tic disorder (TD) is important for planning and assessing therapeutic interventions, neurophysiological mechanisms and predictors of tic exacerbation and remission have not been sufficiently investigated. In each of seven children suffering from TD, contingent negative variation (CNV) was recorded on 10 occasions over a period of 2 months. CNV parameters of children with TD were compared with CNV data of healthy, age-matched children. During the entire time of observation, tic severity was assessed by parents and the investigator using a scale developed from the Yale Global Tic Severity Scale. Moreover, tic severity was also evaluated using video assessments. Patients with TD were characterized by significantly lower amplitude of the total CNV and more pronounced habituation of the early CNV component as compared to healthy children. Correlation analysis between tic severity and CNV parameters demonstrated that the more severe the tics were, the lower the amplitude of the total CNV. Since CNV amplitude represents processes of resource mobilization and control over neuronal excitability, tic severity may result from less ability to control neurophysiological functions in patients with TD.     

Cognitive Control of Saccadic Eye Movements in Children with Developmental Coordination Disorder

The ability to use advance information to prepare and execute a movement requires cognitive control of behaviour (e.g., anticipation and inhibition). Our aim was to explore the integrity of saccadic eye movement control in developmental coordination disorder (DCD) and typically developing (TD) children (8–12 years) and assess how these children plan and inhibit saccadic responses, the principal mechanisms within visual attention control. Eye movements and touch responses were measured (separately and concurrently) in Cued and Non-Cued conditions. We found that children with DCD had similar saccade kinematics to the TD group during saccade initiation. Advance information decreased hand movement duration in both groups during Cued trials, but decrements in accuracy were significantly worse in the DCD group. In addition, children with DCD exhibited greater inhibitory errors and inaccurate fixation during the Cued trials. Thus, children with DCD were reasonably proficient in executing saccades during reflexive (Non-Cued) conditions, but showed deficits in more complex control processes involving prediction and inhibition. These findings have implications for our understanding of motor control in children with DCD.     

注意缺陷多动障碍儿童睡眠障碍与铁缺乏关系 的临床研究

目的:探讨注意缺陷多动障碍(ADHD)患儿睡眠障碍与血清铁蛋白水平的关系。方法:符合美国精神疾病诊断与统计手册第4版(DSM-Ⅳ)中ADHD诊断标准的62例6-14岁ADHD患儿,由ADHD患儿的父母填写睡眠障碍量表(SDSC),检测ADHD患儿的血清铁蛋白水平。结果:与血清铁蛋白水平高于45μg/L的ADHD患儿相比较,血清铁蛋白水平低于45μg/L的ADHD患儿的SDSC"睡眠醒觉转换障碍"项评分和总分明显高于前者(P<0.05)。2组间其他项评分比较无显著性差异(P>0.05)。SDSC"睡眠醒觉转换障碍"项评分与血清铁蛋白水平成负相关(P<0.05)。结论:血清铁蛋白水平低于45μg/LADHD患儿SDSC"睡眠醒觉转换障碍"(睡眠中的异常运动)的危险性显著增加。