Objective: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). Methods: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. Results: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. Conclusion Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.
Humans ; Autism Spectrum Disorder/metabolism* ; Autistic Disorder ; Exome Sequencing ; DNA Copy Number Variations ; East Asian People ; Brain/metabolism* ; Mutation/genetics* ; Genetic Predisposition to Disease/genetics*

Objective: To improve the social skills of children with ASD by using Program for the Education and Enrichment of Relational Skills(PEERS ), and to reduce the uncertainty towards ASD and negative emotions for mothers of ASD children. Methods: From September to October 2017, 30 dyads of autistic mother and child were recruited and divided into intervention group and control group (15 mother child dyads each). Based on the content of PEERS social skill, cognitive behavior therapy was delivered in group format, through demonstration, role play and group exercise. At the same time, mother child dyads were trained using parallel social technology. Mothers and children with ASD were investigated using Parents Perception of Uncertainty Scale (PPUS), Patient Health Questionnaire 9 (PHQ-9), Chinese Version of the Beck Depression Inventory II(BDI-Ⅱ-C), Beck Anxiety Inventory (BAI), State Trait Anxiety Inventory(STAI-Form Y), and Autism Behavior Checklist (ABC), Cildhood Autism Rating Scale (CARS), and Social Communication Questionnaire (SCQ). Results: Changes in ASD symptom score in children and emotional score of mothers in the intervention group were less than 0. The total score of mother disease uncertainty(74.93±13.58, 90.40± 9.21 ), ambiguity(31.13±7.07, 38.93±4.73), lack of clarity information(11.93±2.09, 13.80±2.54), unpredictability(9.60±1.99, 12.07±2.89), significantly changed after intervention( t =-3.65, -3.55, -2.20, -2.72, P <0.05). Conclusion Social PEERS group intervention can enhance the social skills of children with ASD, reduce uncertainty of illness among mother of ASD children. Timely disease related information, guidance for mothers to actively participate in child care and training, might help to reduce cognitive bias, depressive and anxiety symptoms among mothers.

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.

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.
Asian Continental Ancestry Group ; Attention Deficit Disorder with Hyperactivity ; Behavior Rating Scale ; Child ; China ; Executive Function ; Humans ; Interpersonal Relations ; Mass Screening ; Reproducibility of Results ; Self Care ; Self-Control

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.
Adolescent ; Asian Continental Ancestry Group* ; Attention Deficit and Disruptive Behavior Disorders* ; Attention Deficit Disorder with Hyperactivity ; Child* ; Diagnosis ; Executive Function* ; Humans ; Logistic Models ; Neuropsychological Tests ; Social Control, Formal ; Wisconsin

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.

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.

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.

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.