This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multis...This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.展开更多
Background Preschooling is a critical time for intervention in children with autism spectrum disorder(ASD);thus,we analyzed brain tissue component volumes(BTCVs)and clinical indicators in preschool children with ASD t...Background Preschooling is a critical time for intervention in children with autism spectrum disorder(ASD);thus,we analyzed brain tissue component volumes(BTCVs)and clinical indicators in preschool children with ASD to identify new biomarkers for early screening.Methods Eighty preschool children(3–6 years)with ASD were retrospectively included.The whole-brain myelin content(MyC),white matter(WM),gray matter(GM),cerebrospinal fluid(CSF),and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging(SyMRI).Clinical data,such as intelligence scores,autism diagnostic observation schedule-calibrated severity scores,age at first production of single words(AFSW),age at first production of phrases(AFP),and age at walking onset(AWO),were also collected.The correlation between the BTCV and clinical data was evaluated,and the effect of BTCVs on clinical data was assessed by a regression model.Results WM and GM volumes were positively correlated with intelligence scores(both P<0.001),but WM and GM did not affect intelligence scores(P=0.116,P=0.290).AWO was positively correlated with AFSW and AFP(both P<0.001).The multivariate linear regression analysis revealed that MyC,AFSW,AFP,and AWO were significantly different(P=0.005,P<0.001,P<0.001).Conclusions This study revealed positive correlations between WM and GM volumes and intelligence scores.Whole-brain MyC affected AFSW,AFP,and AWO in preschool children with ASD.Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker(abnormal MyC)for early ASD screening in preschool children.展开更多
KMT2D,a H3K4me1 methyltransferase primarily regulating enhancers,is a leading cause of KABUKI syndrome.This multisystem disorder leads to craniofacial and cognitive abnormalities,possibly through neural crest and neur...KMT2D,a H3K4me1 methyltransferase primarily regulating enhancers,is a leading cause of KABUKI syndrome.This multisystem disorder leads to craniofacial and cognitive abnormalities,possibly through neural crest and neuronal lineages.However,the impacted cell-of-origin and molecular mechanism of KMT2D during the development of KABUKI disease remains unknown.Here we have optimized a brain organoid model to investigate neural crest and neuronal differentiation.To pinpoint KMT2D's enhancer target,we developed a genome-wide cis-regulatory element explorer(GREE)based on single-cell multiomic integration.Single cell RNA-seq revealed that KMT2D-knockout(KO)and patient-derived organoids exhibited neural crest deformities and GABAergic overproduction.Mechanistically,GREE identified that KMT2D targets a roof-plate-like niche cell and activates the niche cell-specific WNT3A enhancer,providing the microenvironment for neural crest and neuronal development.Interestingly,KMT2D-mutated mice displayed decreased WNT3A expression in the diencephalon roof plate,indicating impaired niche cell function.Deleting the WNT3A enhancer in the organoids presented phenotypic similarities to KMT2D-depletion,emphasizing the WNT3A enhancer as the predominant target of KMT2D.Conversely,reactivating WNT signaling in KMT2D-KO rescued the lineage defects by restoring the microenvironment.Overall,our discovery of KMT2D's primary target provides insights for reconciling complex phenotypes of KABUKI syndrome and establishes a new paradigm for dissecting the mechanisms of genetic disorders from genotype to phenotype.展开更多
Background Reading Chinese, a kind of ideogram, relies more on visual cognition. The visuospatial cognitive deficit of Chinese dyslexia is an interesting topic that has received much attention. The purpose of current ...Background Reading Chinese, a kind of ideogram, relies more on visual cognition. The visuospatial cognitive deficit of Chinese dyslexia is an interesting topic that has received much attention. The purpose of current research was to explore the visuopatial cognitive characteristics of Chinese dyslexic children by studying their eye movements via a picture searching test. Methods According to the diagnostic criteria defined by ICD-10, twenty-eight dyslexic children (mean age (10.12±1.42) years) were enrolled from the Clinic of Children Behavioral Disorder in the third affiliated hospital of Sun Yat-sen University. And 28 normally reading children (mean age (10.06±1.29) years), 1:1 matched by age, sex, grade and family condition were chosen from an elementary school in Guangzhou as a control group. Four groups of pictures (cock, accident, canyon, meditate) from Picture Vocabulary Test were chosen as eye movement experiment targets. All the subjects carried out the picture searching task and their eye movement data were recorded by an Eyelink II High-Speed Eye Tracker. The duration time, average fixation duration, average saccade amplitude, fixation counts and saccade counts were compared between the two groups of children. Results The dyslexic children had longer total fixation duration and average fixation duration (F=-7.711, P 〈0.01; F=-4.520, P 〈0.05), more fixation counts and saccade counts (F=-7.498, P 〈0.01; F=-11.040, P 〈0.01), and a smaller average saccade amplitude (F=-29.743, P 〈0.01) compared with controls. But their performance in the picture vocabulary test was the same as those of the control group. The eye movement indexes were affected by the difficulty of the pictures and words, all eye movement indexes, except saccade amplitude, had a significant difference within groups (P 〈0.05). Conclusions Chinese dyslexic children have abnormal eye movements in picture searching, applying slow fixations, more fixations and small and frequent saccades. Their abnormal eye movement mode reflects the poor ability and strategy of visual information processing.展开更多
The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder(ASD) in China's mainland. Children diagnosed with ASD(n = 1064, 228 ...The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder(ASD) in China's mainland. Children diagnosed with ASD(n = 1064, 228 females) were retrospectively included in the analysis. All children were assessed using the Autism Diagnostic Interview-Revised(ADI-R) and Autism Diagnostic Observation Schedule(ADOS). The results showed that girls scored significantly higher in ADI-R socioemotional reciprocity than boys, and also scored lower in ADI-R and ADOS restricted and repetitive behaviors(RRBs). Meanwhile, the proportions of girls who satisfied the diagnostic cut-off scores in the ADI-R RRBs domain were lower than in boys(P / 0.05). Our results indicated that girls with ASD show greater socio-emotional reciprocity than boys. Girls also tended to show fewer RRBs than boys, and the type of RRBs in girls differ from those in boys. The ADI-R was found to be less sensitive in girls, particularly for assessment in the RRBs domain.展开更多
Background Several studies have shown the effectiveness of the Early Start Denver Model(ESDM),but few studies have explored the long-term efficacy of ESDM.This study aimed to explore the efficacy and moderating factor...Background Several studies have shown the effectiveness of the Early Start Denver Model(ESDM),but few studies have explored the long-term efficacy of ESDM.This study aimed to explore the efficacy and moderating factors of ESDM in Chinese toddlers with autism spectrum disorder(ASD)in a longitudinal way.Methods A total of 60 toddlers with ASD were recruited and randomly divided into two groups:ESDM group all received 24 weeks intervention;Control group were waiting for intervention.Baseline assessment(T0)was conducted before intervention,including Gesell Developmental Scale(GDS)and Psycho-educational Profile-3rd Edition(PEP-3).All toddlers with ASD were examined in the first assessment(T1)at 6 months and in the second assessment(T2)at 12 months.Results In T1 assessment,the increments in speech and personal communication development quotient in GDS were significantly larger in the ESDM group than in the control group(P=0.010,0.047).In T2 assessment,the ESDM group had higher elevation in cognitive verbal/preverbal(CVP),social reciprocity and characteristic verbal behaviors assessed by PEP-3(P=0.021,0.046,0.014).In addition,the severity of stereotyped behavior was negatively associated with improvement in CVP.Family income was positively associated with improvement in speech and CVP(all P<0.05).Conclusions ESDM can effectively improve speech and communication in toddlers with ASD after 24-week intervention.More importantly,ESDM can promote cognition and social interaction and can reduce stereotyped verbal behavior in toddlers with ASD in longitudinal observation.The severity of stereotyped behavior and family ecological factors may be considered as affecting the efficacy of ESDM.展开更多
基金supported by the National Health Commission of the People’s Republic of China (201302002,Clinical Trial NCT02200679)。
文摘This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
文摘目的探讨母亲孕期增重、孕前BMI与中国广东汉族人群子代孤独症谱系障碍(autism spectrum disorder,ASD)的关联性及其可能存在的临床意义。方法选取ASD患儿279例、其发育正常同胞25例及年龄匹配的发育正常儿童139例,完善其围产期资料及母亲孕产期资料,并进行统计学分析。结果1)在ASD患儿及其发育正常同胞对照中,母亲2次妊娠期间孕期增重(t=1.221,P=0.234)、孕前体重指数(body mass index,BMI)(t=0.715,P=0.482)差异无统计学意义,校正母亲生产年龄及孕前BMI(或孕期增重)等混杂因素后,2组孕期增重(F=0.024,P=0.878)或孕前BMI(F=0.002,P=0.961)间差异亦无统计学意义。2)ASD患儿及发育正常儿童母亲孕期增重(t=-0.390,P=0.696)、孕前BMI(t=0.715,P=0.482)间的差异无统计学意义,对混杂因素进行校正后,2组母亲孕期增重(F=0.374,P=0.541)或孕前BMI(F=0.016,P=0.898)间的差异无统计学意义。结论母亲孕期增重及孕前BMI可能与中国广东汉族人群子代ASD的发病无显著相关。
基金supported by grants from the National Natural Science Foundation of China(No.81801757)Guangdong Basic and Applied Basic Research Foundation(Nos.2022A1515010369 and 2023A1515010256)Guangzhou Municipal Science and Technology Project(No.202201020421).
文摘Background Preschooling is a critical time for intervention in children with autism spectrum disorder(ASD);thus,we analyzed brain tissue component volumes(BTCVs)and clinical indicators in preschool children with ASD to identify new biomarkers for early screening.Methods Eighty preschool children(3–6 years)with ASD were retrospectively included.The whole-brain myelin content(MyC),white matter(WM),gray matter(GM),cerebrospinal fluid(CSF),and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging(SyMRI).Clinical data,such as intelligence scores,autism diagnostic observation schedule-calibrated severity scores,age at first production of single words(AFSW),age at first production of phrases(AFP),and age at walking onset(AWO),were also collected.The correlation between the BTCV and clinical data was evaluated,and the effect of BTCVs on clinical data was assessed by a regression model.Results WM and GM volumes were positively correlated with intelligence scores(both P<0.001),but WM and GM did not affect intelligence scores(P=0.116,P=0.290).AWO was positively correlated with AFSW and AFP(both P<0.001).The multivariate linear regression analysis revealed that MyC,AFSW,AFP,and AWO were significantly different(P=0.005,P<0.001,P<0.001).Conclusions This study revealed positive correlations between WM and GM volumes and intelligence scores.Whole-brain MyC affected AFSW,AFP,and AWO in preschool children with ASD.Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker(abnormal MyC)for early ASD screening in preschool children.
基金supported by National Science Foundation of China(32225012)National Key R&D Program of China(2019YFA0110200)+5 种基金Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong SAR,China,Youth Innovation Promotion Association,Chinese Academy of Sciences(Jie Wang),National Science Foundation of China(32000414,32000503,and 32000501)The Science and Technology Program of Guangzhou 201804020052 and 202102021039the Pearl River Talent Recruitment Program(2021ZT09Y233)Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,(GIBHBRP23-01,GIBHBRP23-02)Frontier Science Research Program of the CAS ZDBS-LY-SM007Science and Technology Planning Project of Guangdong Province,China(2023B1212060050 and 2023B1212120009)。
文摘KMT2D,a H3K4me1 methyltransferase primarily regulating enhancers,is a leading cause of KABUKI syndrome.This multisystem disorder leads to craniofacial and cognitive abnormalities,possibly through neural crest and neuronal lineages.However,the impacted cell-of-origin and molecular mechanism of KMT2D during the development of KABUKI disease remains unknown.Here we have optimized a brain organoid model to investigate neural crest and neuronal differentiation.To pinpoint KMT2D's enhancer target,we developed a genome-wide cis-regulatory element explorer(GREE)based on single-cell multiomic integration.Single cell RNA-seq revealed that KMT2D-knockout(KO)and patient-derived organoids exhibited neural crest deformities and GABAergic overproduction.Mechanistically,GREE identified that KMT2D targets a roof-plate-like niche cell and activates the niche cell-specific WNT3A enhancer,providing the microenvironment for neural crest and neuronal development.Interestingly,KMT2D-mutated mice displayed decreased WNT3A expression in the diencephalon roof plate,indicating impaired niche cell function.Deleting the WNT3A enhancer in the organoids presented phenotypic similarities to KMT2D-depletion,emphasizing the WNT3A enhancer as the predominant target of KMT2D.Conversely,reactivating WNT signaling in KMT2D-KO rescued the lineage defects by restoring the microenvironment.Overall,our discovery of KMT2D's primary target provides insights for reconciling complex phenotypes of KABUKI syndrome and establishes a new paradigm for dissecting the mechanisms of genetic disorders from genotype to phenotype.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30671771).Acknowledgements: We are grateful to the children and their teachers who participated in this research.
文摘Background Reading Chinese, a kind of ideogram, relies more on visual cognition. The visuospatial cognitive deficit of Chinese dyslexia is an interesting topic that has received much attention. The purpose of current research was to explore the visuopatial cognitive characteristics of Chinese dyslexic children by studying their eye movements via a picture searching test. Methods According to the diagnostic criteria defined by ICD-10, twenty-eight dyslexic children (mean age (10.12±1.42) years) were enrolled from the Clinic of Children Behavioral Disorder in the third affiliated hospital of Sun Yat-sen University. And 28 normally reading children (mean age (10.06±1.29) years), 1:1 matched by age, sex, grade and family condition were chosen from an elementary school in Guangzhou as a control group. Four groups of pictures (cock, accident, canyon, meditate) from Picture Vocabulary Test were chosen as eye movement experiment targets. All the subjects carried out the picture searching task and their eye movement data were recorded by an Eyelink II High-Speed Eye Tracker. The duration time, average fixation duration, average saccade amplitude, fixation counts and saccade counts were compared between the two groups of children. Results The dyslexic children had longer total fixation duration and average fixation duration (F=-7.711, P 〈0.01; F=-4.520, P 〈0.05), more fixation counts and saccade counts (F=-7.498, P 〈0.01; F=-11.040, P 〈0.01), and a smaller average saccade amplitude (F=-29.743, P 〈0.01) compared with controls. But their performance in the picture vocabulary test was the same as those of the control group. The eye movement indexes were affected by the difficulty of the pictures and words, all eye movement indexes, except saccade amplitude, had a significant difference within groups (P 〈0.05). Conclusions Chinese dyslexic children have abnormal eye movements in picture searching, applying slow fixations, more fixations and small and frequent saccades. Their abnormal eye movement mode reflects the poor ability and strategy of visual information processing.
基金supported by the National Natural Science Foundation of China (81471017)a Scientific Project of the Ministry of Health of China (201302002)
文摘The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder(ASD) in China's mainland. Children diagnosed with ASD(n = 1064, 228 females) were retrospectively included in the analysis. All children were assessed using the Autism Diagnostic Interview-Revised(ADI-R) and Autism Diagnostic Observation Schedule(ADOS). The results showed that girls scored significantly higher in ADI-R socioemotional reciprocity than boys, and also scored lower in ADI-R and ADOS restricted and repetitive behaviors(RRBs). Meanwhile, the proportions of girls who satisfied the diagnostic cut-off scores in the ADI-R RRBs domain were lower than in boys(P / 0.05). Our results indicated that girls with ASD show greater socio-emotional reciprocity than boys. Girls also tended to show fewer RRBs than boys, and the type of RRBs in girls differ from those in boys. The ADI-R was found to be less sensitive in girls, particularly for assessment in the RRBs domain.
基金This study was supported by grants from the Scientific Research project of National Health Commission(No:201302002)National Natural Science Foundation of China(No:81873801)+1 种基金Technology Program of Guangzhou,China(No:201903010040)Science and Technology Program of Guangzhou(202007030011).
文摘Background Several studies have shown the effectiveness of the Early Start Denver Model(ESDM),but few studies have explored the long-term efficacy of ESDM.This study aimed to explore the efficacy and moderating factors of ESDM in Chinese toddlers with autism spectrum disorder(ASD)in a longitudinal way.Methods A total of 60 toddlers with ASD were recruited and randomly divided into two groups:ESDM group all received 24 weeks intervention;Control group were waiting for intervention.Baseline assessment(T0)was conducted before intervention,including Gesell Developmental Scale(GDS)and Psycho-educational Profile-3rd Edition(PEP-3).All toddlers with ASD were examined in the first assessment(T1)at 6 months and in the second assessment(T2)at 12 months.Results In T1 assessment,the increments in speech and personal communication development quotient in GDS were significantly larger in the ESDM group than in the control group(P=0.010,0.047).In T2 assessment,the ESDM group had higher elevation in cognitive verbal/preverbal(CVP),social reciprocity and characteristic verbal behaviors assessed by PEP-3(P=0.021,0.046,0.014).In addition,the severity of stereotyped behavior was negatively associated with improvement in CVP.Family income was positively associated with improvement in speech and CVP(all P<0.05).Conclusions ESDM can effectively improve speech and communication in toddlers with ASD after 24-week intervention.More importantly,ESDM can promote cognition and social interaction and can reduce stereotyped verbal behavior in toddlers with ASD in longitudinal observation.The severity of stereotyped behavior and family ecological factors may be considered as affecting the efficacy of ESDM.