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*

Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis often presents with a mental disorder as the first symptom, which is more common in middle-aged and older men. However, adolescent females suffer from CASPR2 antibody-related encephalitis, while schizophrenia is rarely reported. This article reports a case of CASPR2 antibody-related encephalitis, ovarian cyst, and schizophrenia in a young female. Due to the complexity of clinical symptoms, the particularity of the course of the disease, and the richness of the diagnosis and treatment process, through the detection, diagnosis, and treatment of this disease, The process description of the case is expected to increase doctors′ experience in diagnosis and treatment of such comorbidities, and to increase the attention to adolescents suffering from CASPR2 antibody-related encephalitis.

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.

Objective:To examine the association between parental characteristics and risk of autism spectrum disorder (ASD) in children.Methods:In this case-control study, the cases were defined as children who were diagnosed with ASD and were recruited from June 2018 to February 2019 in Shanghai Mental Center ( n=104). The controls were defined as children who did not have ASD and were recruited in the two community health centers in Jing-an District of Shanghai during the same period ( n=149). All children recruited in this study were 2-6 years old. A multivariate logistic regression model was used to examine the association between parental characteristics and the risk of ASD in offspring, and further to estimate the interaction coefficient. Results:According to multivariate regression analysis, the association between maternal age, previous pregnancy complication and the risk of ASD in children appeared to be not statistically significant. After adjusted, advanced paternal age (≥35 years old)( OR=3.65, 95% CI=1.19-11.15, P=0.023), parental disease before or during pregnancy ( OR=3.34, 95% CI=1.41-7.94, P=0.006) and gender of child (male) ( OR=5.84, 95% CI=2.98-11.44, P<0.001) were associated with increased risk of ASD. The results also showed that the boys whose father was 35 years old or more had a higher risk of ASD than the boys whose fahter was less 35 years old and the girls whose father was 35 years old or more ( P=0.005, P=0.006). Conclusion:Advanced paternal age was associated with increased risk of ASD in offspring and this effect may be more pronounced in boys.

Objective:To examine the association between parental characteristics and risk of autism spectrum disorder (ASD) in children.Methods:In this case-control study, the cases were defined as children who were diagnosed with ASD and were recruited from June 2018 to February 2019 in Shanghai Mental Center ( n=104). The controls were defined as children who did not have ASD and were recruited in the two community health centers in Jing-an District of Shanghai during the same period ( n=149). All children recruited in this study were 2-6 years old. A multivariate logistic regression model was used to examine the association between parental characteristics and the risk of ASD in offspring, and further to estimate the interaction coefficient. Results:According to multivariate regression analysis, the association between maternal age, previous pregnancy complication and the risk of ASD in children appeared to be not statistically significant. After adjusted, advanced paternal age (≥35 years old)( OR=3.65, 95% CI=1.19-11.15, P=0.023), parental disease before or during pregnancy ( OR=3.34, 95% CI=1.41-7.94, P=0.006) and gender of child (male) ( OR=5.84, 95% CI=2.98-11.44, P<0.001) were associated with increased risk of ASD. The results also showed that the boys whose father was 35 years old or more had a higher risk of ASD than the boys whose fahter was less 35 years old and the girls whose father was 35 years old or more ( P=0.005, P=0.006). Conclusion:Advanced paternal age was associated with increased risk of ASD in offspring and this effect may be more pronounced in boys.

Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis often presents with a mental disorder as the first symptom, which is more common in middle-aged and older men. However, adolescent females suffer from CASPR2 antibody-related encephalitis, while schizophrenia is rarely reported. This article reports a case of CASPR2 antibody-related encephalitis, ovarian cyst, and schizophrenia in a young female. Due to the complexity of clinical symptoms, the particularity of the course of the disease, and the richness of the diagnosis and treatment process, through the detection, diagnosis, and treatment of this disease, The process description of the case is expected to increase doctors′ experience in diagnosis and treatment of such comorbidities, and to increase the attention to adolescents suffering from CASPR2 antibody-related encephalitis.

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