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.

Understanding Autism Spectrum Disorder(ASD)Unraveling the Mysteries(A Short Review)

Autism Spectrum Disorder(ASD)is a multifaceted neurodevelopmental condition characterized by a spectrum of symptoms and behaviors,challenging to fully comprehend due to its variability.This article provides an overview of ASD,including its characteristics,prevalence,diagnosis,and causes.The prevalence of ASD has been on the rise,with improved awareness and diagnostic tools.While genetics and environmental factors play a role,the exact causes remain elusive.Early intervention and various therapies are crucial for improving outcomes,although there is no cure.Ongoing research aims to uncover the complexities of ASD and develop effective treatments.Embracing diversity and fostering inclusion is essential for supporting individuals with ASD.As we continue to unravel the mysteries of ASD,we move closer to a more understanding and inclusive society.This article explores the role of Transcranial Magnetic Stimulation(TMS)in the treatment of Autism Spectrum Disorder(ASD).TMS,a non-invasive neurostimulation technique,is gaining attention as a potential therapy to address specific aspects of ASD.

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.

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.

Diagnosis of Autism Spectrum Disorder by Imperialistic Competitive Algorithm and Logistic Regression Classifier

Autism spectrum disorder(ASD),classified as a developmental disability,is now more common in children than ever.A drastic increase in the rate of autism spectrum disorder in children worldwide demands early detection of autism in children.Parents can seek professional help for a better prognosis of the child’s therapy when ASD is diagnosed under five years.This research study aims to develop an automated tool for diagnosing autism in children.The computer-aided diagnosis tool for ASD detection is designed and developed by a novel methodology that includes data acquisition,feature selection,and classification phases.The most deterministic features are selected from the self-acquired dataset by novel feature selection methods before classification.The Imperialistic competitive algorithm(ICA)based on empires conquering colonies performs feature selection in this study.The performance of Logistic Regression(LR),Decision tree,K-Nearest Neighbor(KNN),and Random Forest(RF)classifiers are experimentally studied in this research work.The experimental results prove that the Logistic regression classifier exhibits the highest accuracy for the self-acquired dataset.The ASD detection is evaluated experimentally with the Least Absolute Shrinkage and Selection Operator(LASSO)feature selection method and different classifiers.The Exploratory Data Analysis(EDA)phase has uncovered crucial facts about the data,like the correlation of the features in the dataset with the class variable.

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.

The Electrophysiology of Semantic Processing in Individuals with Autism Spectrum Disorder:A Meta-Analysis

Language difficulties vary widely among people with autism spectrum disorder(ASD).However,the semantic processing of autistic person and its underlying electrophysiological mechanism are still unclear.This meta-analysis aimed to explore the disturbance of semantic processing in patients with ASD.PubMed,Web of Science,and Embase were searched for eventrelated potential(ERP)studies on semantic processing in autistic people published in English before September 01,2022.Pooled estimates were calculated by fixed-effects or random-effects models according to the heterogeneity using Comprehensive Meta-Analysis 2.0.The potential moderators were explored by meta-regression and subgroup analysis.This meta-analysis has been registered at the Prospero International Prospective Register of Systematic Reviews(no.CRD 42021265852).A total of 14 articles and 18 studies,including 254 autistic people and 262 neurodevelopmental people were included in this meta-analysis.Compared to the comparison group,autistic people showed an overall reduced N400 amplitude(Hedges’g=0.350,p<0.001)in response to linguistic stimuli instead of non-linguistic stimuli.The N400 amplitude was affected by verbal intelligence and gender.The reduced overall N400 amplitude in autistic people under linguistic stimuli suggests a linguistic-specific deficit in semantic processing in individuals of autism.The decrease of N400 amplitude might be a promising indication of the pool language capacity of autism.

Video-Based Interventions for Adolescents and Young Adults with Autism Spectrum Disorder:A Systematic

Many individuals with autism spectrum disorder(ASD)experience delays in the development of social and communications skills,which can limit their opportunities in higher education and employment resulting in an overall negative impact to their quality of life.This systematic review identifies 15 studies that explored the effectiveness of Video-Based Interventions(VBIs)for those with ASD during the critical years of adolescence and young adulthood.The 15 studies described herein found this to be an effective intervention for this population for the improvement of their vocational,daily living,and academic skills.In addition,VBIs allow for the maintenance and generalization of the different target behaviors that were examined.The majority of the studies located by this review also investigated the social validity of the intervention method with participants and caregivers and found these VBIs to have high social validity.Although a few studies that implemented VBIs to improve academic skills were located,the research on their use in this area was found to be lacking,indicating a gap in the research on VBIs.Increased usage of VBIs—including video modeling and video prompting—with the target population of those aged 15–28 with ASD is recommended with specific attention given to the use of VBIs to improve the academic and social skills of adolescents and young adults with ASD.

Consistent and Specific Multi-View Functional Brain Networks Fusion for Autism Spectrum Disorder Diagnosis

Functional brain networks (FBN) based on resting-state functional magnetic resonance imaging (rs-fMRI) have become an important tool for exploring underlying organization patterns in the brain, which can provide an objective basis for brain disorders such as autistic spectrum disorder (ASD). Due to its importance, researchers have proposed a number of FBN estimation methods. However, most existing methods only model a type of functional connection relationship between brain regions-of-interest (ROIs), such as partial correlation or full correlation, which is difficult to fully capture the subtle connections among ROIs since these connections are extremely complex. Motivated by the multi-view learning, in this study we propose a novel Consistent and Specific Multi-view FBNs Fusion (CSMF) approach. Concretely, we first construct multi-view FBNs (i.e., multiple types of FBNs modelling various relationships among ROIs), and then these FBNs are decomposed into a consistent representation matrix and their own specific matrices which capture their common and unique information, respectively. Lastly, to obtain a better brain representation, it is fusing the consistent and specific representation matrices in the latent representation spaces of FBNs, but not directly fusing the original FBNs. This potentially makes it more easily to find the comprehensively brain connections. The experimental results of ASD identification on the ABIDE datasets validate the effectiveness of our proposed method compared to several state-of-the-art methods. Our proposed CSMF method achieved 72.8% and 76.67% classification performance on the ABIDE dataset.

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.

Exploring the Lives of Mothers Raising Children with Autism Spectrum Disorder in Japan

Background: Examining the lives that mothers experience and build will allow us to deepen our understanding of children with ASD and their mothers and facilitate developing support methods. The study aimed to examine the lives of mothers raising children with autism spectrum disorder (ASD) and investigate their sources of support. Method: We conducted a qualitative inductive study using semi-structured interviews to identify characteristics of the lives that mothers have created. Results: Semi-structured interviews were conducted with 11 mothers having children with ASD. The analysis comprised three stages of coding and yielded eight categories. The lives of these mothers contained three themes: preoccupation with parenting children with ASD and their siblings;evolving mother;and using social resources. Mothers engaged in “assessing the characteristics, growth, and changes in the child with ASD”, had a “preoccupation with parenting children with ASD”, and were “thinking about the future of the child with ASD”, and “having goals and plans for parenting” while having “consideration toward the child’s siblings”. During this process, mothers experienced “changes in perspective or approach” and created lifestyles while “receiving help from people around them” and engaged in the “use of social resources”. Conclusions: To avoid becoming preoccupied with parenting and being burdened by their lifestyle, mothers require social support to monitor their perceptions. Furthermore, the utilization of social resources requires the supporting individuals to understand the characteristics of children with ASD, provide appropriate information, and assist in decision-making.

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.

Prevalence and Early Signs of Autism Spectrum Disorder(ASD) among 18-36 Month Old Children in Tianjin of China

Objective The aim of this study is to estimate the prevalence of autism spectrum disorder(ASD) among 18-36 month old children in the Tianjin Municipality of China, and to identify early signs of autistic children and the predictability of each individual symptom. Methods A total of 8 000 children were screened to do a questionnaire based on CHAT modified to include more early signs of autism at the age of 18-36 months. Then the at-risk children were reexamined 1.5 years later and ASD children were identified based on DSM-IV. Early signs of autism were analyzed retrospectively by using discriminant function analysis performed among ASD children, children not followed up and children followed up but failing to meet ASD criteria. Results Three hundred and sixty seven children were screened as being at-risk to ASD, and 22 of them were identified as having ASD in the subsequent diagnosis. The prevalence of ASD was 27.5 per 10 000 in Tianjin of China with a male to female ratio of 4:1. Items addressing social interactions and communications had higher predictability than other items to distinguish autistic children from non-autistic ones. Pretend play, functional play, showing and reading parents' facial expressions distinguished autistic children from those not followed up, nevertheless those followed up but failing to meet ASD criteria were not included. Conclusion The prevalence of ASD found in our study was lower than that reported in some studies by western researchers. Autism has its specific symptoms, such as deficits in social awareness, social relatedness, and social referencing.

Efficacy of Static and Intermittent Gravity Inverted Therapy Techniques in Improvement of Motor Apraxia and Cognitive Abilities in Autism Spectrum Disorder (ASD)

This work was carried out to investigate the efficacy of static and intermittent gravity inverted therapy techniques in improvement of motor apraxia and cognitive abilities in Autism Spectrum Disorder (ASD). 30 children were randomly joined in this study into two groups;Group A (sensory integration therapy approach plus static and intermittent inversion therapy techniques) and Group B (sensory integration therapy approach only). Block design test was used to locate and follow constructional apraxia, computerized information processing speed test to locate and follow cognitive processing and grooved pegboard test was used to locate and follow fine motor skills. The variance between pre- and post-treatment results was highly significant in the study group in all variables. By comparison of the two groups in constructional apraxia variables test at post-treatment, there was a highly representative elevation in favour to study groups (p < 0.05). By comparison of the two groups in cognitive processing variable at post-treatment, there was a highly representative elevation in favour to study group (p < 0.05). By comparison of the two groups in fine motor skills variable at post-treatment, there was a highly representative elevation in favor to study group (p < 0.05). According to the outcomes of this study, it can be terminated that the sensory integration therapy approach plus static and intermittent inversion therapy techniques can be recommended in improvement constructional apraxia and cognitive processing abilities in autism spectrum disorder (ASD) children.

Genetic mechanisms underlying synaptic pathology in Autism Spectrum Disorder (ASD)

Autism spectrum disorder(ASD)is a neuronal developmental disorder that is characterized by de⁃fects both in social interaction and verbal communication,and is often accompanied by restricted interest,and repeti⁃tive and stereotyped behaviors.The prevalence of ASD is approximately 0.8%~1.2%in China.Although its etiology remains unclear in most cases,over 1000 genes or genomic loci have been linked to its pathogenic origin,indicating a strong genetic influence,as well as complicated pathogenic mechanisms.Here,we reviewed recent findings in the possible genetic effects on synaptic pathophysiology of ASD,and a particular focus was put on variants in genes that are related to synaptic morphology or functions,such as FMR1,NRXN,NLGN,SHANK and MeCP2.The synaptic pathology caused by these genetic defects may substantially contribute to the pathogenesis of ASD.This review out⁃lines several lines of evidence that have been recently reported to support the hypothesis that a genetic defect may lead to a synaptic pathology that may underlie the pathogenesis of ASD.

Does playing a sports active video game improve object control skills of children with autism spectrum disorder?

Background: Active video games(AVGs) encourage whole body movements to interact or control the gaming system, allowing the opportunity for skill development. Children with autism spectrum disorder(ASD) show decreased fundamental movement skills in comparison with their typically developing(TD) peers and might benefit from this approach. This pilot study investigates whether playing sports AVGs can increase the actual and perceived object control(OC) skills of 11 children with ASD aged 6–10 years in comparison to 19 TD children of a similar age.Feasibility was a secondary aim.Methods: Actual(Test of Gross Motor Development) and perceived OC skills(Pictorial Scale of Perceived Movement Skill Competence for Young Children) were assessed before and after the intervention(6 × 45 min).Results: Actual skill scores were not improved in either group. The ASD group improved in perceived skill. All children completed the required dose and parents reported the intervention was feasible.Conclusion: The use of AVGs as a play-based intervention may not provide enough opportunity for children to perform the correct movement patterns to influence skill. However, play of such games may influence perceptions of skill ability in children with ASD, which could improve motivation to participate in physical activities.

Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders

Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells(MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD.Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review willfocus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

Neuropsychiatric Symptoms,Parenting Stress and Social Support in Chinese Mothers of Children with Autism Spectrum Disorder

Although little is known about the current situation regarding autism spectrum disorder(ASD)in main land China,psychiatric disorders are common among Chinese mothers of preschool children with ASD.Previous studies showed ASD child's behavioral symptoms,maternal anxiety,and maternal depressive symptoms were associated with overall parenting stress in northern China.In the present study,we retrospectively analyzed medical records at the hospital related to neuropsychiatric symptoms,parenting stress and social support in mothers of children with ASD from southern China.A total of 80 mothers of children with ASD were screened.Among them,34 mothers were in low-functioning ASD group(L-ASD group)and 46 mothers were in highfunctioning ASD group(H-ASD group).Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory.Neuropsychiatric symptoms,parenting stress and social support were measured by neuropsychiatric inventory(NPI),parenting stress index short form(PSISF),and multi-dimensional scale of perceived social support(MSPSS).Total mean score of the NPI in the L-ASD group was significantly higher than that in the H-ASD group(P<0.01).The subscale scores of NPI,including depression,anxiety,apathy,irritability,agitation,night time behavior disturbances and change in appetite were significantly higher in the L-ASD group than those in the H-ASD group(P<0.01 or P<0.05).Meanwhile,the total PSI-SF scores and the scores of parental distress(PD),parental-child dysfunctional interaction(PCDI)and difficult child(DC)in the L-ASD group were significantly higher than those in the H-ASD group(P<0.01 or P<0.05).The total score of MSPSS was also higher in the L-ASD group than in the H-ASD group(P<0.01).This study goes further to show the neuropsychiatric symptoms and parenting stress are significantly higher in mothers of children with ASD,and more social supports are needed for mothers of children with ASD from southern China,especially for mothers of children with low-functioning ASD.

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.

Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder:A Systematic Review of Clinical Trials

The therapeutic potentials of probiotics in autism spectrum disorder(ASD)remains controversial,with the only existing systematic review on this topic published in 2015.Results from new trials have become available in recent years.We therefore conducted an updated systematic review,to assess the efficacy of probiotics in relieving behavioral symptoms of ASD and gastrointestinal comorbidities.Our review includes two randomized controlled trials,which showed improvement of ASD behaviors,and three open trials,all which exhibited a trend of improvement.Four of these trials concluded from subjective measures that gastrointestinal function indices showed a trend of improvement with probiotic therapy.Additional rigorous trials are needed to evaluate the effects of probiotic supplements in ASD.