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Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.
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OBJECTIVE: This research developed a practical, multi-dimensional attention deficit hyperactivity disorder (ADHD) rating scale (i.e., the Symptoms and Functional Impairment Rating Scale, SFIRS) for Chinese children, aged 6–12 years, with ADHD. METHODS: The structural validity, criterion validity, internal consistency, and test-retest reliability of the scale were evaluated. Item screening was conducted with 412 ADHD patients and 322 developmentally typical controls. RESULTS: The scale includes 44 items, divided among Hyperactivity-Impulsivity, Self-Control, Inattention, Self-Management, Academic Performance, and Social Interaction. The six-factor model showed good data fit, with each factor significantly correlated with its corresponding criterion (r=0.690–0.841). The Cronbach's α of the full scale was 0.976. Total score test-retest reliability was r=0.816 (p < 0.01). CONCLUSION: The SFIRS thus demonstrated good reliability and validity and may be used to assess ADHD among children aged 6–12 years in China.
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Child , Humans , Asian People , Attention Deficit Disorder with Hyperactivity , Behavior Rating Scale , China , Executive Function , Interpersonal Relations , Mass Screening , Reproducibility of Results , Self Care , Self-ControlABSTRACT
Objective The number of children diagnosed with autism spectrum disorder (ASD)has increased dramatically in the past years.Parents of children with ASD usually experience a variety of chronic and acute stressors that may decrease marital satisfaction and family functioning.The aim was to explore the characteristics of parental per-sonality,mood disorders and family functions of the Children with ASD and to explore the relevance factors in order to draw out methods to improve parental family functions.Methods A cross -sectional survey was conducted and 593 outpatients with ASD diagnosed in Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine form January 201 0 to January 201 4 were straight into the group,their parents were tested by Family Assessment Device (FAD),Zung Self -Rating Depression Scale(SDS),Zung Self -Rating Anxiety Scale(SAS)and Eysenck Personality Questionnaire(EPQ).SPSS 1 7.0 software was adopted to establish the database and statistical analysis.Results Ac-cording to FAD,parents of children with ASD had lower scores in problem solving[(2.1 0 ±0.37)scores]and roles [(2.09 ±0.27)scores](t =-6.669,P =0.000;t =-1 8.707,P =0.000)than the standard scores,while other di-mensions score were significantly higher than the standard scores in communicdtion[(2.25 ±0.35)scores],emotional reaction[(2.38 ±0.40)scores],emotional involvement[(2.36 ±0.37)scores],behavioral control[(2.31 ±0.27) scores]and general function[(2.1 2 ±0.38)scores],there were significant differences(t =3.1 35,1 1 .1 1 5,1 6.997, 37.1 1 6,8.064;P =0.002,0.000,0.000,0.000,0.000).For EPQ of parents,mother had obviously higher scores than father in psychoticism scale[(53.68 ±1 .36)scores vs (52.65 ±1 .1 7)scores,t =-1 3.841 ,P =0.000],and signifi-cantly lower scores in Lie scale[(52.27 ±0.79)scores vs (52.1 7 ±0.75)scores,t =2.449,P =0.01 4].Compared to fathers,mothers were coded as higher depression and anxiety scores(t =-6.276,-6.440,all P =0.000)and higher prevalence rate(χ2 =1 5.893,27.592,all P =0.000),which were statistically significant.According to the asso-ciation study of FAD and the others(especially in mood of parents),it was found that several dimensions showed obvious correlation.Conclusions Parents of children with ASD have family function damaged badly,except for prob-lem solving and roles.The parents showed different personality traits and mood disorders,particularly mothers′mood disorder problem was prominent.Parental family functioning were closely related to their personality traits and emotional disorders in various dimensionalities,which was worthy of attention.
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OBJECTIVE: This study aims to explore the feature of emotional regulation and executive functions in oppositional defiant disorder (ODD) children. METHODS: The emotional regulation and executive functions of adolescents with ODD, as well as the relationship between the two factors were analyzed using tools including Adolescent Daily Emotional Regulation Questionnaire (ADERQ), Wisconsin Card Sorting Test (WCST) and Cambridge Neuropsychological Test Automated Battery (CANTAB), in comparison with attention deficit hyperactivity disorder (ADHD) children without behavioral problem and healthy children; the ADERQ assessed emotional regulation ability and others were used to assess executive function. RESULTS: Compared to normal children, the ODD group displayed significant differences in the scores of cognitive reappraisal, rumination, expressive suppression, and revealing of negative emotions, as well as in the score of cognitive reappraisal of positive emotions. WCST perseverative errors were well correlated with rumination of negative emotions (r=0.47). Logistic regression revealed that the minimum number of moves in the Stocking of Cambridge (SOC) test (one test in CANTAB) and negative emotion revealing, were strongly associated with ODD diagnosis. CONCLUSION: Children with ODD showed emotion dysregulation, with negative emotion dysregulation as the main feature. Emotion dysregulation and the lack of ability to plan lead to executive function deficits. The executive function deficits may guide us to understand the deep mechanism under ODD.
Subject(s)
Adolescent , Child , Humans , Asian People , Attention Deficit and Disruptive Behavior Disorders , Attention Deficit Disorder with Hyperactivity , Diagnosis , Executive Function , Logistic Models , Neuropsychological Tests , Social Control, Formal , WisconsinABSTRACT
Objective:To assess the validity and reliability of the Chinese version of the eleven-item Kutcher Adolescent Depression Scale (KADS-11)in Chinese adolescents,calculate its optimal cut-off value and the sensi-tivity and specificity,and explore the possibility of providing a useful tool to assess the severity of adolescent de-pressive symptoms.Methods:Totally 3180 students aged 11 -17 years were selected from schools in 6 provinces and Shanghai.All of them were asked to complete the KADS-11 and Children Depression Inventory (CDI). Students whose CDI scores were above 19 (including 19)were diagnosed with the DSM-IV criteria of depressive disorder,73 students from Shanghai sample were assessed with KADS-11 and CDI to analyze the test-retest reliabil-ity 1 month later.Results:Exploratory factor analysis showed that KADS-11 had 2 factors,and confirmatory factor analysis tested proved the 2-factor model fit better than the one-factor model.The KADS-11 total scores were posi-tively correlated with CDI total scores (r =0.74,P <0.01 ),and the KADS-11 scores were higher in depressive group than those in non-depressive group.The mean area under the curve (AUC)of KADS-11was 0.94,the mean area under the curve of each item ranged from 0.7 to 0.9.The optimal cut-off point of KADS-11 was total score≥9,sensitivity and specificity were 89% and 90% respectively.The Cronbach's alpha coefficient of the KADS-11 was 0.84,the spilt-half reliability coefficient was 0.71 (P <0.01),and the test-retest coefficient was 0.77 (P <0.01).Conclusion:The KADS-11 is appropriate for Chinese adolescents because of its good validity,reliability and diagnosis accuracy,it could be used to assess depressive symptoms for adolescents.
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Objective To investigate the prevalence of autism spectrum disorders (ASD) of children aged 4-6 years in public kindergartens in Shanghai.Methods Songjiang district and Xuhui district were selected randomly as the representative sample.By means of "Clancy Autism Behavior Scale","Social Communication Questionnaire" and "high-functioning Autism Spectrum Screening Questionnaire",all of the 33 public kindergartens in chosen area,which contained 10 385 children aged 4-6 years,were surveyed.Those who were screened as suspected cases would be further diagnosed by "Autism Diagnostic Interview-Revised" and "Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition".Results Among 9 665 valid questionnaires,9 children were diagnosed with ASD.The ratio of male to female was 8:1,the point prevalence rate was 0.93‰.The results of ADI-R corresponded with that of DSM-5.There were two children who never had medical records.For others,"language" problem was the most likely reason for their parents to seek medical help,while "deficits in social communication" was the main symptom of patients.Conclusion The prevalence of ASD was lower than those recorded in literature,home and abroad which might be related to some patients not going to public kindergartens.
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Attention deficit hyperactivity disorder(ADHD) is one of the most common psychiatric disorders among school-age children.The diagnosis and treatment of ADHD rely on a comprehensive evaluation of symptom,functional impairment and comorbidity.Therefore the standardized rating scales is widely used clinically.The standardized rating scales can be categorized into: Broad-band scales,evaluating the general misbehavior and sociopsychological functions andNarrow-band scales,evaluating ADHD specific symptoms,and also functional impairment rating scales.Useful comorbidity and functional impairment rating scales are in need domestically.This paper reviewed the published literature about the clinical application and progression of frequently-used rating scales for school-age ADHD evaluation,at home and abroad.
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Objective To explore the correlation of single nucleotide polymorphism (SNP) with PTEN gene involving in mammalian target of rapamycin (mTOR) C1 signaling genes polymorphisms and autism in children.Methods A total of 97 cases with autism were enrolled from Mar.2011 to Dec.2012 in this study,who came from the child and adolescent out-patient department in Shanghai Mental Health Center of Shanghai Jiaotong University School of Medicine.Single SNP association and haplotype association analysis were performed using the family-based association test and Haploview software.Results 1.In a family-based association test,two SNPs showed significant association with autism(rs17107001 G:Z =2.982,P =0.003 ; rs2299941 G:Z =2.524,P =0.012).After the correction of false discovery rate,they all remained significant.2.Haplotype association analysis showed significant transmission disequilibrium in haplotype T-T-G and C-T-A generated from rs532678-rs17562384-rs2299941 (block2) in LD Block,and haplotype T-T-G was over transmitted to offspring(Z =-2.986,P =0.003) while haplotype C-T-A was the opposite (Z =-2.197,P =0.028).Conclusion The SNPs of PTEN genes might have a correlation with autism in children.
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ObjectiveTo investigate the association between catechol-O-methyl transferase (COMT)gene polymorphism and Gilles de la Tourette' s syndrome(GTS).MethodsUsing Amplification Refractory Mutation System(ARMS) PCR genotyping assay method,a polymorphism (val158met) of COMT gene was genotyped in 112 of all GTS patients ( total GTS group) including 54 GTS-alone patients group,48 GTS + ADHD patients group among of them and 71 healthy controls.The correlation between positive association of polymorphism (val158met)of COMT gene in GTS and the age of onset in patients with GTS was also analyzed.ResultsCompared with healthy controls group,genotype of val158met did not differ in total GTS patients group or alone-GTS patients group (χ2 =0.56,P=0.756;χ2 =1.05,P=0.600 respectively).There was also no significant difference (P＞0.05)in allele distribution of val158met in total GTS patients group or alone-GTS patients group compared with controls group respectively (χ2 =0.18,P=0.669;χ2 =0.29,P=0.593 respectively).However,genotype distribution of val158met was significantly different between GTS + ADHD patients group and controls group( χ2 =6.35,P =0.041 ).The frequency of the val allele of this locus was significantly higher in GTS + ADHD patients group than those in controls group ( χ2 =5.49,P =0.019 ).The mean age of onset (6.80 ± 1.54 ) in 36 children within GTS + ADHD patients group with the val/val geantype of COMT gene val158met polymorphism was significantly earlier than the mean age of onset (8.04 ± 1.54)in 12 children in val/val genotype (P =0.016 ).ConclusionPolymorphism (val158met) of COMT gene may be associated with GTS children with comorbid ADHD,which may play an important role to make the age of onset in children with GTS become earlier.
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Objective: To study mental health of children in special families. Method: Achenbach Children Behavior Checklist was used to investigate 2048 children aged 8-16 of divorced family, separation family, spouse-loss family, remarried family, under poverty-line family, child-handicapped family, foster family, parent-handicapped family, criminal family, and orphan in twenty districts/counties of Shanghai. Results: The prevalence of behavior problem of them was 8.1%, while the rate in boys (9.6%) was significantly higher than that in girls (6.4%, ? 2=8.58, P