Expressive Language Profiles in a Clinical Screening Sample of Mandarin-Speaking Preschool Children With Autism Spectrum Disorder.

PURPOSE: This cross-sectional study aimed to depict expressive language profiles and clarify lexical-grammatical interrelationships in Mandarin-speaking preschoolers with autism spectrum disorder (ASD) during the administration of the simplified Chinese Psychoeducational Profile-Third Edition screening. METHOD: We collected naturalistic language samples from 81 (74 boys, seven girls) 2- to 7-year-old (Mage = 55.6 months, SD = 15.17) Mandarin-speaking children with ASD in clinician-child interactions. The child participants were divided into five age subgroups with 12-month intervals according to their chronological age. Computer-assisted part-of-speech tagging, constituency analysis, and dependency analysis addressed the developmental trajectories of early lexical and grammatical growth in each age subgroup. RESULTS: Significant within-ASD differences were observed in content words, function words, and lexical categories. Nouns and verbs were the predominant lexical categories, while noun types overwhelmed verb types in children over 3 years old. The grammatical development of 5- to 6-year-old Mandarin-speaking children with ASD was better than that of 3- to 4-year-old children. The trends of syntactic structures, grammatical relations, and grammatical complexity in each age group were similar. CONCLUSIONS: Mandarin-speaking preschoolers with ASD produce more lexicons with increasing age. They preserve the noun bias as a universal mechanism in early lexical learning. Moreover, their developmental trajectories of grammatical growth were comparable in each age subgroup. In addition, their lexicons and grammar were synchronically developed during early language acquisition.

Simultaneous hydrodynamic cavitation and nanosecond pulse discharge plasma enhanced by oxygen injection.

A novel Hydrodynamic Cavitation-Assisted Oxygen Plasma (HCAOP) process, which employs a venturi tube and oxygen injection, has been developed for enhancing the production and utilization of hydroxyl radicals (·OH) in the degradation of organic pollutants. This study has systematically investigated the fluid characteristics and discharge properties of the gas-liquid two-phase body in the venturi tube. The hydraulic cavitation two-phase body discharge is initiated by the bridging of the cavitation cloud between the electrodes. The discharge mode transitions from diffuse to spark to corona as the oxygen flow rate increases. The spark discharge has the highest current and discharge energy. Excessive oxygen results in the change of the flow from bubbly to annular and a subsequent decrease in discharge energy. The effects of cavitation intensity, oxygen flow rate, and power polarity on discharge characteristics and ·OH production were evaluated using terephthalic acid as a fluorescent probe. It was found that injecting 3 standard liter per minute (SLPM) of oxygen increased the ·OH yield by 6 times with only 1.2 times increase in power, whereas<0.5 SLPM of oxygen did not improve the ·OH yield due to lower breakdown voltage. Negative polarity voltage increased the breakdown voltage and ·OH yield due to asymmetric density and pressure distribution in the throat tube. This polarity effect was explained by numerical simulation. Using indigo carmine (E132) as a model pollutant, the HCAOP process degraded 20 mg/L of dye in 5 L water within 2 min following a first-order reaction. The lowest electric energy per order (EEO) was 0.26 (kWh/m3/order). The HCAOP process is a highly efficient flow-type advanced oxidation process with potential industrial applications.

Adaptation and Feasibility of the Mandarin Version of PEERS® for Autistic Adolescents.

PURPOSE: The Program for the Education and Enrichment of Relational Skills (PEERS®) is a group-based social skills training program for adolescents on the autism spectrum. Although the program has been shown to be effective in improving social skills in autistic adolescents, evidence of its effectiveness from the Mandarin-speaking Chinese population is sparse. The present study used a non-randomized, pre- and post-intervention research design to investigate the feasibility and cultural validity of the program, as well as examine the moderators of intervention outcomes. METHODS: Thirty-three autistic adolescents with intelligence quotient above 70 (Mage = 13.57, SDage = 1.43; Male: Female 25:8) and their parents received 14 concurrent 90-minute sessions. Adolescents' autistic traits, challenging behaviors, emotional functioning, socio-cognitive process, social environment factors (school support), and caregivers' well-being were evaluated. RESULTS: The findings suggest that with minor adjustments, the Mandarin version of PEERS® was generally acceptable and feasible for autistic adolescents and their parents. PEERS® may improve the social skills knowledge, reciprocal communication abilities, and emotional well-being of autistic adolescents. Also, participants with a higher level of school support, and parents with lower perceived subjective well-being at baseline may gain more benefits from PEERS®. The cultural adaptation and acceptability of the Mandarin Version of PEERS® were discussed. CONCLUSION: This feasibility study (Chinese Clinical Trial Registry: ChiCTR2200061417, 2022-06-23, retrospectively registered) provides a basis for further randomized control trials of the Mandarin version of PEERS®.

Examine sex differences in autism spectrum disorder in school-aged children and adolescents with fluent language.

There are noteworthy sex disparities in the prevalence of autism spectrum disorders (ASD), while findings regarding the sex differences in core symptoms are inconsistent. There are few relevant studies on sex differences in mainland China. This study was dedicated to a deeper understanding of the impact of sex differences on the clinical presentation of ASD with fluent language. We retrospectively studied 301 children with ASD (58 females) and utilized raw scores from the ADI-R and ADOS and the intelligence quotient (IQ) to measure symptomatology. Based on the Full-Scale IQ (FS-IQ), a binary split of average, above-average IQ (high-IQ), and below-average IQ (low IQ) occurs at 85. Across the entire sample, males and females are comparable in the FS-IQ, while males scored higher in the Perceptual Reasoning Index (PRI) (F = 7.812, p = 0.006). ADI-R did not find any statistically significant sex differences in the diagnostic cutoff score satisfaction or the raw domain scores. While a significant effect of sex on ADOS social affect domain scores was found in the total sample [λ = 0.970, partial η2 = 0.030, F (3,295) = 3.019, p = 0.030]. Tests of between-subjects effects revealed that males scored higher than females mainly in the ADOS reciprocal social interaction subcategory (partial η2 = 0.022, F = 6.563, p = 0.011). Stratified analysis revealed that the effect of sex on ADOS reciprocal social interaction subcategory scores only significant in the low-IQ children with ASD (partial η2 = 0.092, F = 10.088, p = 0.002). In general, overall cognitive functioning is similar across males and females with ASD, while males have a higher perceptual reasoning ability. Females with ASD are more likely to have comorbid intellectual impairment than males, and they could require additional intervention support. Autistic children with low IQs are more likely to exhibit sex differences in their core symptoms than children with high IQs. Intelligence plays a key role in sex-based differences in the core symptoms of ASD.

Identifying activity level related movement features of children with ASD based on ADOS videos.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects about 2% of children. Due to the shortage of clinicians, there is an urgent demand for a convenient and effective tool based on regular videos to assess the symptom. Computer-aided technologies have become widely used in clinical diagnosis, simplifying the diagnosis process while saving time and standardizing the procedure. In this study, we proposed a computer vision-based motion trajectory detection approach assisted with machine learning techniques, facilitating an objective and effective way to extract participants' movement features (MFs) to identify and evaluate children's activity levels that correspond to clinicians' professional ratings. The designed technique includes two key parts: (1) Extracting MFs of participants' different body key points in various activities segmented from autism diagnostic observation schedule (ADOS) videos, and (2) Identifying the most relevant MFs through established correlations with existing data sets of participants' activity level scores evaluated by clinicians. The research investigated two types of MFs, i.e., pixel distance (PD) and instantaneous pixel velocity (IPV), three participants' body key points, i.e., neck, right wrist, and middle hip, and five activities, including Table-play, Birthday-party, Joint-attention, Balloon-play, and Bubble-play segmented from ADOS videos. Among different combinations, the high correlations with the activity level scores evaluated by the clinicians (greater than 0.6 with p < 0.001) were found in Table-play activity for both the PD-based MFs of all three studied key points and the IPV-based MFs of the right wrist key point. These MFs were identified as the most relevant ones that could be utilized as an auxiliary means for automating the evaluation of activity levels in the ASD assessment.

A multimodal machine learning system in early screening for toddlers with autism spectrum disorders based on the response to name.

Background: Reduced or absence of the response to name (RTN) has been widely reported as an early specific indicator for autism spectrum disorder (ASD), while few studies have quantified the RTN of toddlers with ASD in an automatic way. The present study aims to apply a multimodal machine learning system (MMLS) in early screening for toddlers with ASD based on the RTN. Methods: A total of 125 toddlers were recruited, including ASD (n = 61), developmental delay (DD, n = 31), and typical developmental (TD, n = 33). Procedures of RTN were, respectively, performed by the evaluator and caregiver. Behavioral data were collected by eight-definition tripod-mounted cameras and coded by the MMLS. Response score, response time, and response duration time were accurately calculated to evaluate RTN. Results: Total accuracy of RTN scores rated by computers was 0.92. In both evaluator and caregiver procedures, toddlers with ASD had significant differences in response score, response time, and response duration time, compared to toddlers with DD and TD (all P-values < 0.05). The area under the curve (AUC) was 0.81 for the computer-rated results, and the AUC was 0.91 for the human-rated results. The accuracy in the identification of ASD based on the computer- and human-rated results was, respectively, 74.8 and 82.9%. There was a significant difference between the AUC of the human-rated results and computer-rated results (Z = 2.71, P-value = 0.007). Conclusion: The multimodal machine learning system can accurately quantify behaviors in RTN procedures and may effectively distinguish toddlers with ASD from the non-ASD group. This novel system may provide a low-cost approach to early screening and identifying toddlers with ASD. However, machine learning is not as accurate as a human observer, and the detection of a single symptom like RTN is not sufficient enough to detect ASD.

Efficacy and moderating factors of the Early Start Denver Model in Chinese toddlers with autism spectrum disorder: a longitudinal study.

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.

Parents' knowledge and attitude and behavior toward autism: a survey of Chinese families having children with autism spectrum disorder.

Background: In recent years, parent-mediated intervention for children with autism spectrum disorder (ASD) has increased. Therefore, implementing effective parent training programs for parents of children with autism is of paramount importance, particularly in low- and middle-income countries. However, little is known about the status of and gaps in parents' knowledge on ASD, which may hinder the development of valid parental training programs. Herein, we aimed at exploring the status of Chinese parents' knowledge, attitude and behavior toward ASD, and potential factors affecting the acquisition of correct knowledge. Methods: This study used a self-designed parental knowledge questionnaire of autism (PKQA) comprising 20 questions alongside another questionnaire comprising additional 17 questions covering the aspects of family demographics, attitudes, and behaviors of parents. In total, we included 394 parents who visited the outpatient department of the Child's Development and Behavior Center of the Third Affiliated Hospital of Sun Yat-Sen University between December 2018 and May 2019, with their children meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for ASD. Results: The median knowledge score in the PKQA was 15 [interquartile range (IQR), 13-17]. Advanced paternal age and longer time interval from diagnosis to enrolling into the parent training program were associated with a lower total knowledge score (all P<0.001). Higher maternal education attainment, higher family income, child being currently under intervention, and family members sharing a common perception of the diagnosis were associated with a higher total knowledge score (all P<0.01). Reading autism-related books (P<0.001) or attending professional lectures (P=0.019) were also associated with a higher total knowledge score. Conclusions: Taken together, this study revealed that family demographics and parents' attitudes and behaviors toward ASD may significantly influence their knowledge about autism, suggesting the need for promoting more targeted parental skills training programs.

The role of caregiver gestures and gesture-related responses of toddlers with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by social communicative abnormalities. Deficits and delays in gestural communication are among the early deficits of ASD and also a major social modality in early caregiver-toddler interaction. Caregiver gestures have an important role in the cognitive and social development of children with ASD. Thus, it is urgent to further explore the role of caregiver gestures in early caregiver-toddler interaction. In this cross-sectional study, we observed the caregivers' gestures and responses of toddlers aged between 18 and 24 months during play (ASD = 44, TD = 29) and dining activities (ASD = 34, TD = 27). By observing the different frequencies and patterns of gestures by the caregiver-child interaction and the different proportions of children's responses to the caregiver's gestures, we found that, compared to caregivers of typically developing toddlers, caregivers of toddlers with ASD had fewer synchronized gestures and more unsynchronized gestures in the play activity and more supplementary gestures in dining activity. Toddlers with ASD produced more social responses to caregivers' synchronized gestures, whereas the use of synchronized gestures by the caregivers in caregiver-toddler interaction had a positive influence on social responses to toddlers with ASD. The findings suggest that effective use of gestures by caregivers during caregiver-toddler activities can improve children's social responses.

Application of Clustering Method to Explore the Correlation Between Dominant Flora and the Autism Spectrum Disorder Clinical Phenotype in Chinese Children.

Autism spectrum disorder (ASD) is characterized by deficits in social interactions and repetitive, stereotypic behaviors. Evidence shows that bidirectional communication of the gut-brain axis plays an important role. Here, we recruited 62 patients with ASD in southern China, and performed a cross-sectional study to test the relationship between repeated behavior, gut microbiome composition, and alpha diversity. We divided all participants into two groups based on the clustering results of their microbial compositions and found Veillonella and Ruminococcus as the seed genera in each group. Repetitive behavior differed between clusters, and cluster 2 had milder repetitive symptoms than Cluster 1. Alpha diversity between clusters was significantly different, indicating that cluster 1 had lower alpha diversity and more severe repetitive, stereotypic behaviors. Repetitive behavior had a negative correlation with alpha diversity. We demonstrated that the difference in intestinal microbiome composition and altered alpha diversity can be associated with repetitive, stereotypic behavior in autism. The role of Ruminococcus and Veillonella in ASD is not yet understood.

Discriminative Dictionary Learning for Autism Spectrum Disorder Identification.

Autism Spectrum Disorder (ASD) is a group of lifelong neurodevelopmental disorders with complicated causes. A key symptom of ASD patients is their impaired interpersonal communication ability. Recent study shows that face scanning patterns of individuals with ASD are often different from those of typical developing (TD) ones. Such abnormality motivates us to study the feasibility of identifying ASD children based on their face scanning patterns with machine learning methods. In this paper, we consider using the bag-of-words (BoW) model to encode the face scanning patterns, and propose a novel dictionary learning method based on dual mode seeking for better BoW representation. Unlike k-means which is broadly used in conventional BoW models to learn dictionaries, the proposed method captures discriminative information by finding atoms which maximizes both the purity and coverage of belonging samples within one class. Compared to the rich literature of ASD studies from psychology and neural science, our work marks one of the relatively few attempts to directly identify high-functioning ASD children with machine learning methods. Experiments demonstrate the superior performance of our method with considerable gain over several baselines. Although the proposed work is yet too preliminary to directly replace existing autism diagnostic observation schedules in the clinical practice, it shed light on future applications of machine learning methods in early screening of ASD.

Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary 1H-NMR Metabolomics Analysis.

Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-center study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms. Methods: One hundred and seventeen autistic children and 119 healthy children were recruited from research centers of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA), and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analyzed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis. Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine, and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine, and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine [area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726], creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668), and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism. Conclusions: Urinary amino acid metabolites were significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

LAY ABSTRACT: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.

The Gestures in 2-4-Year-Old Children With Autism Spectrum Disorder.

Deficits in gestures act as early signs of impairment in social interaction (SI) and communication in children with autism spectrum disorder (ASD). However, the pieces of literature on atypical gesture patterns in ASD children are contradictory. This investigation aimed to explore the atypical gesture pattern of ASD children from the dimensions of quantity, communicative function, and integration ability; and its relationship with social ability and adaptive behavior. We used a semi-structured interactive play to evaluate gestures of 33 ASD children (24-48 months old) and 24 typically developing (TD) children (12-36 months old). And we evaluated the social ability, adaptive behavior, and productive language of ASD and TD children by using the Adaptive Behavior Assessment System version II (ABAS-II) and Chinese Communication Development Inventory (CCDI). No matter the total score of CCDI was corrected or not, the relative frequency of total gestures, behavior regulation (BR) gestures, SI gestures, and joint attention (JA) gestures of ASD children were lower than that of TD children, as well as the proportion of JA gestures. However, there was no significant group difference in the proportion of BR and SI gestures. Before adjusting for the total score of CCDI, the relative frequency of gestures without vocalization/verbalization integration and vocalization/verbalization-integrated gestures in ASD children was lower than that in TD children. However, after matching the total score of CCDI, only the relative frequency of gestures without vocalization/verbalization integration was lower. Regardless of the fact that the total score of CCDI was corrected or not, the relative frequency and the proportion of eye-gaze-integrated gestures in ASD children were lower than that in TD children. And the proportion of gestures without eye-gaze integration in ASD children was higher than that in TD children. For ASD children, the social skills score in ABAS-II was positively correlated with the relative frequency of SI gesture and eye-gaze-integrated gestures; the total score of ABAS-II was positively correlated with the relative frequency of total gestures and eye-gaze-integrated gestures. In conclusion, ASD children produce fewer gestures and have deficits in JA gestures. The deficiency of integrating eye gaze and gesture is the core deficit of ASD children's gesture communication. Relatively, ASD children might be capable of integrating vocalization/verbalization into gestures. SI gestures and the ability to integrate gesture and eye gaze are related to social ability. The quantity of gestures and the ability to integrate gesture with eye gaze are related to adaptive behavior. Clinical Trial Registration: www.ClinicalTrials.gov, identifier ChiCTR1800019679.

Comparison of beta diversity measures in clustering the high-dimensional microbial data.

The heterogeneity of disease is a major concern in medical research and is commonly characterized as subtypes with different pathogeneses exhibiting distinct prognoses and treatment effects. The classification of a population into homogeneous subgroups is challenging, especially for complex diseases. Recent studies show that gut microbiome compositions play a vital role in disease development, and it is of great interest to cluster patients according to their microbial profiles. There are a variety of beta diversity measures to quantify the dissimilarity between the compositions of different samples for clustering. However, using different beta diversity measures results in different clusters, and it is difficult to make a choice among them. Considering microbial compositions from 16S rRNA sequencing, which are presented as a high-dimensional vector with a large proportion of extremely small or even zero-valued elements, we set up three simulation experiments to mimic the microbial compositional data and evaluate the performance of different beta diversity measures in clustering. It is shown that the Kullback-Leibler divergence-based beta diversity, including the Jensen-Shannon divergence and its square root, and the hypersphere-based beta diversity, including the Bhattacharyya and Hellinger, can capture compositional changes in low-abundance elements more efficiently and can work stably. Their performance on two real datasets demonstrates the validity of the simulation experiments.

The Development of Brain Network in Males with Autism Spectrum Disorders from Childhood to Adolescence: Evidence from fNIRS Study.

In the current study, functional near-infrared spectroscopy (fNIRS) was used to collect resting-state signals from 77 males with autism spectrum disorders (ASD, age: 6~16.25) and 40 typically developing (TD) males (age: 6~16.58) in the theory-of-mind (ToM) network. The graph theory analysis was used to obtain the brain network properties in ToM network, and the multiple regression analysis demonstrated that males with ASD showed a comparable global network topology, and a similar age-related decrease in the medial prefrontal cortex area (mPFC) compared to TD individuals. Nevertheless, participants with ASD showed U-shaped trajectories of nodal metrics of right temporo-parietal junction (TPJ), and an age-related decrease in the left middle frontal gyrus (MFG), while trajectories of TD participants were opposite. The nodal metrics of the right TPJ was negatively associated with the social deficits of ASD, while the nodal metrics of the left MFG was negatively associated with the communication deficits of ASD. Current findings suggested a distinct developmental trajectory of the ToM network in males with ASD from childhood to adolescence.

Peripheral Blood S100B Levels in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

The S100 calcium-binding protein beta subunit (S100B) protein, which mostly exists in the central nervous system, is commonly noted as a marker of neuronal damage. We conducted the first systematic review with meta-analysis to compare peripheral blood S100B levels in individuals with ASD with those in healthy controls. A systematic search was carried out for studies published before May 5, 2020. In total, this meta-analysis involved ten studies with 822 participants and 451 cases. The meta-analysis revealed that individuals with ASD had higher peripheral blood S100B levels than healthy controls [standardized mean difference (SMD) = 0.97, 95% confidence interval (95% CI) = 0.41-1.53; p < 0.001]. Peripheral blood S100B levels may have potential as a useful biomarker for ASD.

Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.

Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years.

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 was 867 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.