Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance

Objective This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016)for Autism Spectrum Disorder(ASD)screening in the presence of developmental surveillance.Methods All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules(GDS).Spearman’s correlation coefficients and Kappa values were obtained.Taking GDS as a reference assessment,the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic(ROC)curves.The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule,Second Edition(ADOS-2).Results In total,150 children aged 12–42 months with ASD were enrolled.The developmental quotients of the CNBS-R2016 were correlated with those of the GDS(r=0.62–0.94).The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays(Kappa=0.73–0.89),except for Fine Motor.There was a significant difference between the proportions of Fine Motor,delays detected by the CNBS-R2016 and GDS(86.0%vs.77.3%).With GDS as a standard,the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor,which was 0.70.In addition,the positive rate of ASD was 100.0%and 93.5%when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used,respectively.Conclusion The CNBS-R2016 performed well in developmental assessment and screening for children with ASD,especially by Communication Warning Behaviors subscale.Therefore,the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Pathophysiology of autism spectrum disorders:Revisiting gastrointestinal involvement and immune imbalance

Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.

Understanding autism spectrum disorders with animal models:applications,insights,and perspectives

Autism spectrum disorder(ASD)is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors.It is widely accepted that genetic and environmental factors solely or in combination cause ASD.However,the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature.To better understand the pathogenesis of ASD,various animal models have been generated,which can be generally divided into genetic,environment-induced,and idiopathic animal models.In this review,we summarize the common animals used for ASD study and then discuss the applications,clinical insights,as well as challenges and prospects of current ASD animal models.

Association Analysis of Genetic Variant of rs13331 in PSD95 Gene with Autism Spectrum Disorders：A Case-control Study in a Chinese Population

Autism spectrum disorder（ASD） is a neurodevelopmental disorder characterized by high heritability. Recently, autism, the most profound form of ASD, has been increasingly attributed to synaptic abnormalities. Postsynaptic density 95（PSD95）, encoding PSD protein-95, was found essential for synaptic formation, maturation and plasticity at a PSD of excitatory synapse. It is possibly a crucial candidate gene for the pathogenesis of ASD. To identify the relationship between the rs13331 of PSD95 gene and ASD, we performed a case-control study in 212 patients and 636 controls in a Chinese population by using a polymerase chain reaction-restriction fragment length polymerase（PCR-RFLP） assay. The results showed that in genetic analysis of the heterozygous model, an association between the T allele of the rs13331 and ASD was found in the dominant model（OR=1.709, 95% CI 1.227–2.382, P=0.002） and the additive model（OR=1.409, 95% CI=1.104–1.800, P=0.006）. Our data indicate that the genetic mutation C〉T at the rs13331 in the PSD95 gene is strikingly associated with an increased risk of ASD.

Gastrointestinal disease in children with autism spectrum disorders:Etiology or consequence?

Chronic gastrointestinal(GI)symptoms and disorders are common in children with autism spectrum disorder and have been shown to be significantly correlated with the degree of behavioral and cognitive impairment.In this unique population,GI symptoms often arise very early in development,during infancy or toddlerhood,and may be misdiagnosed-or not diagnosed at all–due in part to the challenges associated with recognition of symptoms in a minimally or noncommunicative child.Evidence demonstrating that the gut-brain-axis can communicate gut dysbiosis and systemic immune dysregulation in a bidirectional manner raises the question as to whether an untreated gastrointestinal disorder can directly impact neurodevelopment or,conversely,whether having a neurodevelopmental disorder predisposes a child to chronic GI issues.From the data presented in this mini review,we conclude that the preponderance of available evidence would suggest the former scenario is more strongly supported.

Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder

The effective intervention strategy for autism spectrum disorder(ASD)are currently limited.Herein,we attempted to evaluate the potential of L-proline(Pro),a multifunctional amino acid,in ameliorating autismlike behaviors and clarify the molecular mechanisms involved by using the typical valproic acid(VPA)-induced mouse model of ASD.Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice.The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition.The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex(PFC)induced by VPA exposure.RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease,neuroactive ligand-receptor interaction,oxidative phosphorylation,and mitogen activated protein kinase signaling pathway.Overall,dietary Pro supplementation may be a promising intervention strategy for ASD.

Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.

Nutritional management and autism spectrum disorder:A systematic review

BACKGROUND Autism spectrum disorder(ASD)presents unique challenges related to feeding and nutritional management.Children with ASD often experience feeding difficulties,including food selectivity,refusal,and gastrointestinal issues.Various interventions have been explored to address these challenges,including dietary modifications,vitamin supplementation,feeding therapy,and behavioral interventions.AIM To provide a comprehensive overview of the current evidence on nutritional management in ASD.We examine the effectiveness of dietary interventions,vitamin supplements,feeding therapy,behavioral interventions,and mealtime practices in addressing the feeding challenges and nutritional needs of children with ASD.METHODS We systematically searched relevant literature up to June 2024,using databases such as PubMed,PsycINFO,and Scopus.Studies were included if they investigated dietary interventions,nutritional supplements,or behavioral strategies to improve feeding behaviors in children with ASD.We assessed the quality of the studies and synthesized findings on the impact of various interventions on feeding difficulties and nutritional outcomes.Data extraction focused on intervention types,study designs,participant characteristics,outcomes measured,and intervention effectiveness.RESULTS The review identified 316 studies that met the inclusion criteria.The evidence indicates that while dietary interventions and nutritional supplements may offer benefits in managing specific symptoms or deficiencies,the effectiveness of these approaches varies.Feeding therapy and behavioral interventions,including gradual exposure and positive reinforcement,promise to improve food acceptance and mealtime behaviors.The findings also highlight the importance of creating supportive mealtime environments tailored to the sensory and behavioral needs of children with ASD.CONCLUSION Nutritional management for children with ASD requires a multifaceted approach that includes dietary modifications,supplementation,feeding therapy,and behavioral strategies.The review underscores the need for personalized interventions and further research to refine treatment protocols and improve outcomes.Collaborative efforts among healthcare providers,educators,and families are essential to optimize this population's nutritional health and feeding practices.Enhancing our understanding of intervention sustainability and long-term outcomes is essential for optimizing care and improving the quality of life for children with ASD and their families.

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

Role of gastrointestinal health in managing children with autism spectrum disorder

Children with autism spectrum disorders(ASD)or autism are more prone to gastrointestinal(GI)disorders than the general population.These disorders can significantly affect their health,learning,and development due to various factors such as genetics,environment,and behavior.The causes of GI disorders in children with ASD can include gut dysbiosis,immune dysfunction,food sensitivities,digestive enzyme deficiencies,and sensory processing differences.Many studies suggest that numerous children with ASD experience GI problems,and effective management is crucial.Diagnosing autism is typically done through genetic,neurological,functional,and behavioral assessments and observations,while GI tests are not consistently reliable.Some GI tests may increase the risk of developing ASD or exacerbating symptoms.Addressing GI issues in individuals with ASD can improve their overall well-being,leading to better behavior,cognitive function,and educational abilities.Proper management can improve digestion,nutrient absorption,and appetite by relieving physical discomfort and pain.Alleviating GI symptoms can improve sleep patterns,increase energy levels,and contribute to a general sense of well-being,ultimately leading to a better quality of life for the individual and improved family dynamics.The primary goal of GI interventions is to improve nutritional status,reduce symptom severity,promote a balanced mood,and increase patient independence.

The complex genetics in autism spectrum disorders

Autism spectrum disorders(ASD) are a pervasive neurodevelopmental disease characterized by deficits in social interaction and nonverbal communication, as well as restricted interests and stereotypical behavior. Genetic changes/heritability is one of the major contributing factors, and hundreds to thousands of causative and susceptible genes, copy number variants(CNVs), linkage regions, and micro RNAs have been associated with ASD which clearly indicates that ASD is a complex genetic disorder. Here, we will briefly summarize some of the high-confidence genetic changes in ASD and their possible roles in their pathogenesis.

Regional cerebral blood flow in children with autism spectrum disorders： a quantitative 99mTc-ECD brain SPECT study with statistical parametric mapping evaluation

Background Autism spectrum disorders （ASD）, which include autism, asperger syndrome （AS） and pervasive developmental disorder-not otherwise specified （PDD-NOS）, are devastating neurodevelopmental disorders of childhood resulting in deficits in social interaction, repetitive patterns of behaviors, and restricted interests and activities. Single photon emission computed tomography （SPECT） is a common technique used to measure regional cerebral blood flow （rCBF）. Several studies have measured rCBF in children with ASD using SPECT, however, findings are discordant. In addition, the majority of subjects used in these studies were autistic. In this study, we aimed to investigate changes in rCBF in children with ASD using SPECT.Methods A Technetium-99m-ethyl cysteinate dimmer （99mTc-ECD） brain SPECT study was performed on an ASD group consisting of 23 children （3 girls and 20 boys; mean age （7.2±3.0） years） who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition （DSM-Ⅳ） criteria and an age-matched control group with 8children （1 girl and 7 boys, mean age （5.5±2.4） years）. Image data were evaluated with Statistical Parametric Mapping,5th version （SPM5）. A Student＇s t test for unpaired data was used to compare rCBF and asymmetry in the autism and corresponding control group. The covariance analysis, taking age as covariance, was performed between the ASD and control group.Results There was a significant reduction in rCBF in the bilateral frontal lobe （frontal poles, arcula frontal gyrus） and the bilateral basal ganglia in the autism group, and a reduction in the bilateral frontal, temporal, parietal, legumina nucleus and cerebellum in the AS group compared to the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group was observed. Inner-group comparison analysis revealed that rCBF decreased significantly in the bilateral frontal lobe （42.7%）, basal nucleus （24.9%） and temporal lobe （22.8%） in the autism group, and in the bilateral cerebellum （22.8%）, basal nucleus （19.3%） and right thalamencephalon （16.6%）in the AS group （P ＜0.05）.Conclusions The decrease in rCBF in ASD is a global event, which involves the bilateral frontal, temporal, limbic system and basal ganglias. Asymmetry of hemispheric hypoperfusion was more obvious in the AS group than the autism group, which indicates a different neurobiological mechanism from that of autism.

Genomic landscapes of Chinese sporadic autism spectrum disordersrevealed by whole-genome sequencing

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.

Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China:A case-control study

Background:Autism spectrum disorders(ASDs)are a set of complex neurobiological disorders.Growing evidence has shown that the microbiota that resides in the gut can modulate brain development via the gut–brain axis.However,direct clinical evidence of the role of the microbiota–gut–brain axis in ASD is relatively limited.Methods:A case-control study of 71 boys with ASD and 18 neurotypical controls was conducted at China-Japan Friendship Hospital.Demographic information and fecal samples were collected,and the gut microbiome was evaluated and compared by 16S ribosomal RNA gene sequencing and metagenomic sequencing.Results:A higher abundance of operational taxonomic units(OTUs)based on fecal bacterial profiling was observed in the ASD group.Significantly different microbiome profiles were observed between the two groups.At the genus level,we observed a decrease in the relative abundance of Escherichia,Shigella,Veillonella,Akkermansia,Provindencia,Dialister,Bifidobacterium,Streptococcus,Ruminococcaceae UCG_002,Megasphaera,Eubacterium_coprostanol,Citrobacter,Ruminiclostridium_5,and Ruminiclostridium_6 in the ASD cohort,while Eisenbergiella,Klebsiella,Faecalibacterium,and Blautia were significantly increased.Ten bacterial strains were selected for clinical discrimination between those with ASD and the neurotypical controls.The highest AUC value of the model was 0.947.Conclusion:Significant differences were observed in the composition of the gut microbiome between boys with ASD and neurotypical controls.These findings contribute to the knowledge of the alteration of the gut microbiome in ASD patients,which opens the possibility for early identification of this disease.

Drosophila Studies on Autism Spectrum Disorders

In the past decade, numerous genes associated with autism spectrum disorders（ASDs） have been identified. These genes encode key regulators of synaptogenesis,synaptic function, and synaptic plasticity. Drosophila is a prominent model system for ASD studies to define novel genes linked to ASDs and decipher their molecular roles in synaptogenesis, synaptic function, synaptic plasticity, and neural circuit assembly and consolidation. Here, we review Drosophila studies on ASD genes that regulate synaptogenesis, synaptic function, and synaptic plasticity through modulating chromatin remodeling, transcription, protein synthesis and degradation, cytoskeleton dynamics, and synaptic scaffolding.

SHANK1 and autism spectrum disorders

Autism spectrum disorders （ASD） are highly heterogeneous pediatric developmental disorders with estimated heritability more than 70%. Although the genetic factors in ASD are mainly unknown, a large number of gene mutations have been found, especially in genes involved in neurogenesis. The Neurexin-Neuroligin-Shank （NRXN-NLGN-SHANK） pathway plays a key role in the formation, maturation and maintenance of synapses, consistent with the hypothesis of neurodevelopmental abnormality in ASD. Presynaptic NRXNs interact with postsynaptic NLGNs in excitatory glutamatergic synapses. SHANK proteins function as core components of the postsynaptic density （PSD） by interacting with multiple proteins. Recently, deletions and point mutations of the SHANK1 gene have been detected in ASD individuals, indicating the involvement of SHANK1 in ASD. This review focuses on the function of SHANK1 protein, Shankl mouse models, and the molecular genetics of the SHANK1 gene in human ASD.

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

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology.Individuals with autism spectrum disorder show deficits in a variety of areas including cognition,memory,attention,emotion recognition,and social skills.With no definitive treatment or cure,the main interventions for individuals with autism spectrum disorder are based on behavioral modulations.Recently,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 disorder.Preliminary 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 disorder.However,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 stimulation.The 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.

Associations between meeting 24-hour movement guidelines and quality of life among children and adolescents with autism spectrum disorder

Background:The Canadian 24-hour movement behavior(24-HMB)guidelines suggest that a limited amount of screen time use,an adequate level of physical activity(PA),and sufficient sleep duration are beneficial for ensuring and optimizing the health and quality of life(QoL)of children and adolescents.However,this topic has yet to be examined for children and adolescents with autism spectrum disorder(ASD)specifically.The aim of this cross-sectional observational study was to examine the associations between meeting 24-HMB guidelines and several QoLrelated indicators among a national sample of American children and adolescents with ASD.Methods:Data were taken from the 2020 U.S.National Survey of Children’s Health dataset.Participants(n=956)aged 617 years and currently diagnosed with ASD were included.The exposure of interest was adherence to the 24-HMB guidelines.Outcomes were QoL indicators,including learning interest/curiosity,repeating grades,adaptive ability,victimization by bullying,and behavioral problems.Categorical variables were described with unweighted sample counts and weighted percentages.Age,sex,race,preterm birth status,medication,behavioral treatment,household poverty level,and the educational level of the primary caregivers were included as covariates.Odds ratio(OR)and 95%confidence interval(95%CI)were used to present the strength of association between adherence to 24-HMB guidelines and QoL-related indicators.Results:Overall,452 participants(45.34%)met 1 of the 3 recommendations,216(22.65%)met 2 recommendations,whereas only 39 participants(5.04%)met all 3 recommendations.Compared with meeting none of the recommendations,meeting both sleep duration and PA recommendations(OR=3.92,95%CI:1.639.48,p<0.001)or all 3 recommendations(OR=2.11,95%CI:1.034.35,p=0.04)was associated with higher odds of showing learning interest/curiosity.Meeting both screen time and PA recommendations(OR=0.15,95%CI:0.040.61,p<0.05)or both sleep duration and PA recommendations(OR=0.24,95%CI:0.070.87,p<0.05)was associated with lower odds of repeating any grades.With respect to adaptive ability,participants who met only the PA recommendation of the 24-HMB were less likely to have difficulties dressing or bathing(OR=0.11,95%CI:0.020.66,p<0.05)than those who did not.For participants who met all 3 recommendations(OR=0.38,95%CI:0.150.99,p=0.05),the odds of being victimized by bullying was lower.Participants who adhered to both sleep duration and PA recommendations were less likely to present with severe behavioral problems(OR=0.17,95%CI:0.040.71,p<0.05)than those who did not meet those guidelines.Conclusion:Significant associations were found between adhering to 24-HMB guidelines and selected QoL indicators.These findings highlight the importance of maintaining a healthy lifestyle as a key factor in promoting and preserving the QoL of children with ASD.

Modernising autism spectrum disorder model engineering and treatment via CRISPR-Cas9:A gene reprogramming approach

A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns are another feature of the illness.Multiple mutations throughout development are the source of the neurodevelopmental disorder autism.However,a well-established model and perfect treatment for this spectrum disease has not been discovered.The rising era of the clustered regularly interspaced palindromic repeats(CRISPR)-associated protein 9(Cas9)system can streamline the complexity underlying the pathogenesis of ASD.The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner.The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD.Therefore,CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines,in vitro 3D organoid models and in vivo animal models.Apart from being used in establishing ASD models,CRISPR-Cas9 can also be used to treat the complexities of ASD.The aim of this review was to summarize and critically analyse the CRISPRCas9-mediated discoveries in the field of ASD.

Review of evolution of clinical, training and educational services and research program for autism spectrum disorders in Hong Kong

The evolution of a local fragmented model of services for children with autism in Hong Kong emerged gradually over the past three decades with lack of government funding or support. This had been due to increasing number of children with autism being detected and referred for earlier assessment. With increasing pressure from parents due to long waiting time for assessment and training services and the increasing polarization by mass media there had been a gradual increasing public awareness over the past five years. Though still highly fragmented in the availability of services, there is a growing "business model" available in the community due to increasing need and lack of public funding for support. There is a lack of strategic planning for medical diagnostic and management issues in Hong Kong. Our University of Hong Kong based Autism Research Program was pioneered in 1985 based on the increasing load of autism cases referred for assessment for other developmental problems and diagnosed as Autism in the Duchess of Kent Children's Hospital. As the first author has been the staff of the University of Hong Kong, this program flourished as a research based program. The benefits of early identification and intervention of autism spectrum disorder(ASD) had been increasingly recognized, and with the increased public awareness and increasing trend of earlier diagnosis, there has been a continuously high demand from parents for earlier assessment and training for children suspected to have ASD. This model had not received extra funding for this integrated program for research, teaching and training in autism. We had to apply for various donations and grants to support the development of this pioneer program. The research output and organization of forums for public education and awareness are reviewed. The latter part of the paper reports the summary of clinical profile of autism cases(N=1441) assessed from 1985 to 2010 June under the University of Hong Kong. As the waiting time for initial developmental assessment for any children in Hong Kong is 12?24 months, we also report our preliminary experience with a newly launched triaging service provision for children suspected to be ASD since 2009, including multi-disciplinary assessment and parallel interim training in our university affiliated child assessment centre in Hong(N=89).