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Association of CDH11 with autism spectrum disorder Revealed by Matched-gene Co-expression Analysis and Mouse Behavioral Studies

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Neuroscience Bulletin 2022年第1期38卷 29-46页

作者： Nan Wu Yue Wang Jing-Yan Jia Yi-Hsuan Pan Xiao-Bing Yuan Key Laboratory of Brain Functional Genomics of Shanghai and the Ministry of Education Institute of Brain Functional GenomicsSchool of Life Science and the Collaborative Innovation Center for Brain ScienceEast China Normal UniversityShanghai200062China Hussman Institute for autism Baltimore21201USA Department of Anatomy and Neurobiology University of Maryland School of MedicineBaltimore21201USA

A large number of putative risk genes for autism spectrum disorder(ASD)have been *** functions of most of these susceptibility genes in developing brains remain unknown,and causal relationships between their variation and autism traits have not been *** aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes(hcASDs).The results showed that three gene features–gene size,mRNA abundance,and guanine-cytosine content–affect the genome-wide co-expression profiles of *** circumvent the interference of these features in gene co-expression analysis,we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched *** method is referred to as"matched-gene co-expression analysis"(MGCA).With MGCA,we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene *** results of analysis of two recently-reported ASD candidate genes,CDH11 and CDH9,suggested the involvement of CDH11,but not CDH9,in *** with this prediction,behavioral studies showed that Cdh11-null mice,but not Cdh9-null mice,have multiple autism-like behavioral *** study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.

关键词： CDH11 autism spectrum disorder Gene co-expression analysis Matched-gene co-expression analysis

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Prevalence of autism spectrum disorder in China:A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years

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Neuroscience Bulletin 2020年第9期36卷 961-971页

作者： Hao Zhou Xiu Xu Weili Yan Xiaobing Zou Lijie Wu Xuerong Luo Tingyu Li Yi Huang Hongyan Guan Xiang Chen Meng Mao Kun Xia Lan Zhang Erzhen Li Xiaoling Ge Lili Zhang Chunpei Li Xudong Zhang Yuanfeng Zhou Ding Ding Andy Shih Eric Fombonne Yi Zheng Jisheng Han Zhongsheng Sun Yong-hui Jiang Yi Wang LATENT-NHC Study Team Department of Neurology Children’s Hospital of Fudan UniversityShanghai 201102China Child Health Care Children’s Hospital of Fudan UniversityShanghai 201102China Department of Clinical Epidemiology Children’s Hospital of Fudan UniversityShanghai 201102China Child Development Behavior Center The Third Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510630China Department of Children and Adolescent Health School of Public HealthHarbin Medical UniversityHarbin 150081China Department of Psychiatry The Second Xiangya Hospital of Central South UniversityChangsha 410011China Child Health Care Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Psychiatry West China Hospital of Sichuan UniversityChengdu 610041China Capital Institute of Pediatrics Beijing 100020China The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University Wenzhou 325027China Child Health Care Chengdu Women and Children’s HospitalChengdu 610091China Center for Medical Genetics School of Life SciencesCentral South UniversityChangsha 410013China Children’s Hospital of Fudan University Shanghai 201102China Huashan Hospital of Fudan University Shanghai 200040China autism Speaks 1 East 33rd StreetNew YorkNY 10016USA Oregon Health and Science University PortlandOR 97239USA Beijing Anding Hospital Capital Medical UniversityBeijing 10008&China Neuroscience Research Institute Peking UniversityBeijing 100191China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100021China Department of Genetics and Pediatrics Yale School of MedicineNew HavenCT 06520USA

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese *** targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster *** Modified Chinese autism spectrum Rating Scale was used for the screening *** 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 *** observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall *** 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 *** findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.

关键词： autism spectrum disorder Prevalence Comorbidity autism spectrum Rating Scale China

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Performance of the autism spectrum Rating Scale and Social Responsiveness Scale in Identifying autism spectrum disorder Among Cases of Intellectual Disability

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Neuroscience Bulletin 2018年第6期34卷 972-980页

作者： Chunpei Li Hao Zhou Tianqi Wang Shasha Long Xiaonan Du Xiu Xu Weili Yan Yi Wang Department of Neurology Children's Hospital of Fudan University Department of Pediatrics Guizhou Provincial People's Hospital Medical College of Guizhou University Department of Child Health Children's Hospital of Fudan University Department of Clinical Epidemiology Children's Hospital of Fudan University State Key Laboratory of Medical Neurobiology Fudan University

The autism spectrum Rating Scale(ASRS) and the Social Responsiveness Scale(SRS) have been widely used for screening autism spectrum disorder(ASD) in the general population during epidemiological studies, but studies of individuals with intellectual disability(ID) are quite limited. Therefore, we recruited the parents/caregivers of 204 ASD cases, 71 ID cases aged 6–18 years from special education schools, and 402 typically developing(TD) children in the same age span from a communitybased population to complete the ASRS and SRS. The results showed that the ID group scored significantly lower on total and subscale scores than the ASD group on both scales(P \ 0.05) but higher than TD children(P \ 0.05).Receiver operating characteristic analyses demonstrated a similar fair performance in discriminating ASD from ID with the ASRS(area under the curve(AUC) = 0.709,sensitivity = 77.0%, specificity = 52.1%, positive predictive value(PPV) = 82.2%) and the SRS(AUC = 0.742,sensitivity = 59.8%, specificity = 77.5%, PPV = 88.4%).The results showed that individuals with ID had clear autistic traits and discriminating ASD from ID cases was quite challenging, while assessment tools such as ASRS and SRS, help to some degree.

关键词： autism spectrum disorder Intellectual disability Screening accuracy autism spectrum Rating Scale Social Responsiveness Scale

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Pre-conceptional and prenatal exposure to secondhand smoke and autism spectrum disorder:a national multi-center study in China

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世界儿科杂志:英文版 2023年第8期19卷 761-769页

作者： Li-Zi Lin Xiao-Xuan Ou Xiao-Ling Zhan Xin Wang Li Cai Xiu-Hong Li Jin Jing Guang-Hui Dong Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment Department of Occupational and Environmental HealthSchool of Public HealthSun Yat-Sen University74 Zhongshan 2nd RoadYuexiu DistrictGuangzhou510080China Department of Maternal and Child Health School of Public HealthSun Yat-Sen University74 Zhongshan 2Nd RoadYuexiu DistrictGuangzhou510080China

Background Despite extensive research evaluating the association between prenatal exposure to secondhand smoke(SHS)and the development of autism spectrum disorders(ASD),no study has investigated the association by considering the pre-conceptional *** study aimed to investigate the associations of pre-conceptional and prenatal SHS exposure and the development of ASD among *** In this cross-sectional study,parents of 6049 toddlers aged 16–30 months were recruited from 7 tertiary hospitals,21 communities,and 7 kindergartens located in seven cities in six provinces from five geographical regions of *** analyzed the associations of SHS exposure and the odds of ASD among toddlers in different exposure windows(pre-conceptional and/or prenatal periods).Data were analyzed from November 2021 to January *** Among the 6049 toddlers included in the analysis[22.7(4.1)months;44.8%girls],71 were identified and diagnosed with *** with the unexposed toddlers,toddlers with pre-conceptional SHS exposure had higher odds of ASD(OR 2.30,95%CI 1.36–3.84),while we observed a non-significantly positive association regarding prenatal SHS *** considering both pre-conceptional and prenatal periods,toddlers who were continuously exposed to SHS during these two periods had higher odds than those without SHS exposure(OR 2.32,95%CI 1.24–4.14).Conclusion We reported positive SHS–ASD associations when exposed during the pre-conceptional period and continuously exposed during pre-conceptional and prenatal periods,emphasizing the critical window of pre-conception for targeted intervention on smoking.

关键词： autism spectrum disorder China Epidemiology Pre-conception Secondhand smoke

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Role of Microtubule-Associated Protein in autism spectrum disorder

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Neuroscience Bulletin 2018年第6期34卷 1119-1126页

作者： Qiaoqiao Chang Hua Yang Min Wang Hongen Wei Fengyun Hu Department of Neurology Shanxi Provincial People's Hospital Affiliate of Shanxi Medical University

autism spectrum disorder(ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with repetitive and restrictive patterns of behaviors or interests. Normal brain development is crucial to behavior and cognition in adulthood. Abnormal brain development, such as synaptic and myelin dysfunction, is involved in the pathogenesis of ASD. Microtubules and microtubule-associated proteins(MAPs) are important in regulating the processes of brain development, including neuron production and synaptic formation, as well as myelination. Increasing evidence suggests that the level of MAPs are changed in autistic patients and mouse models of ASD. Here, we discuss the roles of MAPs.

关键词： autism spectrum disorder Microtubuleassociated proteins Synapse Myelin

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Structural,Functional,and Molecular Imaging of autism spectrum disorder

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Neuroscience Bulletin 2021年第7期37卷 1051-1071页

作者： Xiaoyi Li Kai Zhang Xiao He Jinyun Zhou Chentao Jin Lesang Shen Yuanxue Gao Mei Tian Hong Zhang Department of Nuclear Medicine and Medical PET Center The Second Hospital of Zhejiang University School of MedicineHangzhou 310009China Key Laboratory of Medical Molecular Imaging of Zhejiang Province Hangzhou 310009China Key Laboratory for Biomedical Engineering of Ministry of Education Zhejiang UniversityHangzhou 310027China Laboratory for Pathophysiological and Health Science RIKEN Center for Biosystems Dynamics ResearchHyogo 650-0047Japan Department of Surgical Oncology The Second Hospital of Zhejiang University School of MedicineHangzhou 310009China Institute of Nuclear Medicine and Molecular Imaging Zhejiang UniversityHangzhou 310009China The College of Biomedical Engineering and Instrument Science of Zhejiang University Hangzhou 310027China

autism spectrum disorder(ASD)is a heterogeneous neurodevelopmental disorder associated with both genetic and environmental *** approaches have been widely employed to parse the neurophysiological mechanisms underlying ASD,and provide critical insights into the anatomical,functional,and neurochemical *** reviewed recent advances in neuroimaging studies that focused on ASD by using magnetic resonance imaging(MRI),positron emission tomography(PET),or single-positron emission tomography(SPECT).Longitudinal structural MRI has delineated an abnormal developmental trajectory of ASD that is associated with cascading neurobiological processes,and functional MRI has pointed to disrupted functional neural ***,PET and SPECT imaging have revealed that metabolic and neurotransmitter abnormalities may contribute to shaping the aberrant neural circuits of *** large-scale,multi-center,multimodal investigations are essential to elucidate the neurophysiological underpinnings of ASD,and facilitate the development of novel diagnostic biomarkers and better-targeted therapy.

关键词： autism spectrum disorder Positron emission tomography Magnetic resonance imaging Molecular imaging Functional connectivity Serotonin Oxytocin

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Association of neonatal blood levels of brain-derived neurotrophic factor with development of autism spectrum disorder:a systematic review and meta-analysis

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World Journal of Pediatrics 2021年第2期17卷 164-170页

作者： Ya-Kun Liu Hua Gao Shao-Bin Jin Wen-Jun Tu Ya-Jun Chen Department of General Surgery Beijing Children’s HospitalCapital Medical UniversityNo.56 Nanlishi St.Beijing 100045China Department of Pediatric Surgery Qilu Hospital of Shandong UniversityNo.107 West Wenhua StJinan 250000China Institute of Radiation Medicine Chinese Academy of Medical SciencePeking Union Medical CollegeNo.238 Baidi StTianjin 300192China Key Lab of Cerebral Microcirculation in Universities of Shandong Shandong First Medical UniversityShandong Academy of Medical SciencesNo.619 Changcheng St.Taian 271000China

Background Our goal was to evaluate the association between neonatal blood brain-derived neurotrophic factor(BDNF)level and autism spectrum disorder(ASD)diagnosis later in *** MEDLINE and Web of Science databases were searched from inception until September 16,*** lists of all relevant articles also were *** blood BDNF concentrations,standard deviations,sample sizes,and other data needed for calculation of effect sizes were extracted by two independent *** quality of the included studies was appraised using the Newcastle-Ottawa Scale for case-control *** were pooled using the random-effects *** Five case-control studies involving 1341 cases and 3395 controls were included in the *** meta-analysis of all included studies showed no significant difference in blood BDNF levels between neonates diagnosed with ASD later in life and healthy controls[standardized mean difference(SMD)=0.261;95%confidence interval(CI)-0.052 to 0.573;P=0.102],with high level of heterogeneity(Q=64.346;I2=93.784;P<0.001).A subgroup analysis by assay type showed decreased blood BDNF levels in ASDs compared to controls(SMD=—0.070;95%CI-0.114 to-0.026;P=0.002),with high level of homogeneity(Q=0.894;I2=0.000;P=0.827).No evidence of publication bias was *** Neonates diagnosed with ASD later in life have decreased blood levels of BDNF measured by double-antibody *** studies are warranted to facilitate a more robust conclusion.

关键词： autism spectrum disorder Autistic disorder Brain-derived neurotrophic factor Neonates Neurotrophins

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Brain structure underlying the empathizing–systemizing difference in children with autism spectrum disorder

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世界儿科杂志:英文版 2023年第8期19卷 782-792页

作者： Ning Pan Li-Zi Lin Xin Wang Lei Shi Xiao-Yu Xu Yu-Ying Jin Si Tan Xiao-Jing Song Jin Jing Xiu-Hong Li Department of Maternal and Child Health School of Public HealthSun Yat-Sen UniversityNo.74 Zhongshan Road 2Yuexiu DistrictGuangzhou510080China Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment Department of Occupational and Environmental HealthSchool of Public HealthSun Yat-Sen UniversityGuangzhou510080China Key Laboratory of Brain Cognition and Education ScienceMinistry of EducationGuangzhouChina Institute for Brain Research and Rehabilitation and Guangdong Key Laboratory of Mental Health and Cognitive ScienceSouth China Normal UniversityGuangzhou510631China JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research College of PharmacyJinan UniversityGuangzhou510632China Chinese Institute for Brain Research Beijing102206China

Background Behavioral research has shown that children with autism spectrum disorder(ASD)have a higher empathizing–systemizing difference(D score)than normal ***,there is no research about the neuroanatomical mechanisms of the empathizing–systemizing difference in children with *** Participants comprised 41 children with ASD and 39 typically developing(TD)children aged 6‒12 ***–systemizing difference was estimated using the D score from the Chinese version of Children’s Empathy Quotient and Systemizing *** quantified brain morphometry,including global and regional brain volumes and surface-based cortical measures(cortical thickness,surface area,and gyrification)via structural magnetic resonance *** We found that the D score was significantly negatively associated with amygdala gray matter volume[β=−0.16;95%confidence interval(CI):−0.30,−0.02;P value=0.030]in children with *** was a significantly negative association between D score and gyrification in the left lateral occipital cortex(LOC)in children with ASD(B=−0.10;SE=0.03;cluster-wise P value=0.006)and a significantly positive association between D score and gyrification in the right fusiform in TD children(B=0.10;SE=0.03;cluster-wise P value=0.022).Moderation analyses demonstrated significant interactions between D score and diagnosed group in amygdala gray matter volume(β=0.19;95%CI 0.04,0.35;P value=0.013)and left LOC gyrification(β=0.11;95%CI 0.05,0.17;P value=0.001)but not in right fusiform gyrification(β=0.08;95%CI−0.02,0.17;P value=0.105).Conclusions Neuroanatomical variation in amygdala volume and gyrification of LOC could be potential biomarkers for the empathizing–systemizing difference in children with ASD but not in TD ***-scale neuroimaging studies are necessary to test the replicability of our findings.

关键词： autism spectrum disorder Empathy Structural magnetic resonance imaging Systemizing

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Recent advancements in noninvasive brain modulation for individuals with autism spectrum disorder

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Neural Regeneration Research 2023年第6期18卷 1191-1195页

作者： Jessica R.Griff Jake Langlie Nathalie B.Bencie Zachary J.Cromar Jeenu Mittal Idil Memis Steven Wallace Alexander E.Marcillo Rahul Mittal Adrien A.Eshraghi Hearing Research and Communication disorders Laboratory Department of OtolaryngologyNeurotology DivisionUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Neurological Surgery University of Miami Miller School of MedicineMiamiFLUSA Department of Biomedical Engineering University of MiamiCoral GablesFLUSA Department of Pediatrics University of Miami Miller School of MedicineMiamiFLUSA

autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive *** with autism spectrum disorder show deficits in a variety of areas including cognition,memory,attention,emotion recognition,and social *** no definitive treatment or cure,the main interventions for individuals with autism spectrum disorder are based on behavioral ***,noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity,particularly in individuals with autism spectrum *** evidence from small cohort studies,pilot studies,and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum ***,little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial *** objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.

关键词： autism spectrum disorder behavior cognition neurostimulation interventions noninvasive brain modulation theta burst stimulation transcranial direct current stimulation transcranial magnetic stimulation

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Postzygotic mosaic mutations in autism spectrum disorder and other neuropsychiatric disorders

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Science Bulletin 2017年第24期62卷 1624-1625页

作者： Longze Sha Qi Xu State Key Laboratory of Medical Molecular Biology & Neuroscience center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 China

autism, or autism spectrum disorder （ASD）, refers to a range of neurodevelopmental disorders characterized by：（1） impaired social interaction, （2） impaired verbal and non-verbal communication, and （3） restricted and repetitive behavior. Although Wpically not diagnosed until the age of 3, symptoms can present during infancy. Early intervention with behavioral therapies has been shown to improve learning, communication, and social skills. This means it is essential to find a method for evaluating characteristics associated with ASD as early as possible .

关键词： Postzygotic mosaic mutations autism spectrum disorder other neuropsychiatric disorders

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