Autism spectrum disorder:difficulties in diagnosis and microRNA biomarkers

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

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.

Autism spectrum disorder and personality disorders: Comorbidity and differential diagnosis

BACKGROUND Differential diagnosis,comorbidities and overlaps with other psychiatric disorders are common among adults with autism spectrum disorder(ASD),but clinical assessments often omit screening for personality disorders(PD),which are especially common in individuals with high-functioning ASD where there is less need for support.AIM To summarize the research findings on PD in adults with ASD and without intellectual disability,focusing on comorbidity and differential diagnosis.METHODS PubMed searches were performed using the key words“Asperger’s Syndrome”,“Autism”,“Personality”,“Personality disorder”and“comorbidity”in order to identify relevant articles published in English.Grey literature was identified through searching Google Scholar.The literature reviews and reference sections of selected papers were also examined for additional potential studies.The search was restricted to studies published up to April 2020.This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method.RESULTS The search found 22 studies carried out on ASD adults without intellectual disability that met the inclusion criteria:16 evaluated personality profiles or PD in ASD(comorbidity),five compared ASD and PD(differential diagnosis)and one performed both tasks.There were significant differences in the methodological Cluster A and cluster C PD are the most frequent co-occurring PD,but overlapping features should be considered.Data on differential diagnosis were only found with cluster A and cluster B PD.CONCLUSION ASD in high-functioning adults is associated with a distinct personality profile even if variability exists.Further studies are needed to explore the complex relationship between ASD and PD.

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.

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.

Facial Image-Based Autism Detection:A Comparative Study of Deep Neural Network Classifiers

Autism Spectrum Disorder(ASD)is a neurodevelopmental condition characterized by significant challenges in social interaction,communication,and repetitive behaviors.Timely and precise ASD detection is crucial,particularly in regions with limited diagnostic resources like Pakistan.This study aims to conduct an extensive comparative analysis of various machine learning classifiers for ASD detection using facial images to identify an accurate and cost-effective solution tailored to the local context.The research involves experimentation with VGG16 and MobileNet models,exploring different batch sizes,optimizers,and learning rate schedulers.In addition,the“Orange”machine learning tool is employed to evaluate classifier performance and automated image processing capabilities are utilized within the tool.The findings unequivocally establish VGG16 as the most effective classifier with a 5-fold cross-validation approach.Specifically,VGG16,with a batch size of 2 and the Adam optimizer,trained for 100 epochs,achieves a remarkable validation accuracy of 99% and a testing accuracy of 87%.Furthermore,the model achieves an F1 score of 88%,precision of 85%,and recall of 90% on test images.To validate the practical applicability of the VGG16 model with 5-fold cross-validation,the study conducts further testing on a dataset sourced fromautism centers in Pakistan,resulting in an accuracy rate of 85%.This reaffirms the model’s suitability for real-world ASD detection.This research offers valuable insights into classifier performance,emphasizing the potential of machine learning to deliver precise and accessible ASD diagnoses via facial image analysis.

Behavioral and cognitive core domains shared between autism spectrum disorder and schizophrenia

Growing genetic evidence including results of genome-wide association studies and whole-genome sequencing is still perplexing scientists in the fields of human complex traits and compels them to reconsider the relationship between autism spectrum disorder (ASD) and schizophrenia. The developmental trajectory of schizophrenia may be characterized by difficulties in “theory of mind” tasks, poor insight or imagination, low empathy level, weak executive function, failure in social judgments, delayed language development, movement mannerisms, motoric rituals, strong preoccupation with unusual objects, bizarre habits, and high intelligence. Most of these characteristics are associated with the standard criteria for ASD and all of them are core domains or endophenotypes of ASD. The diagnosed ASD cases, which were found in individuals with schizophrenia, have a significant tendency to be highfunctioning and to have atypical age of ASD manifestation. Episodic features including reality distortion, which can be seen in individual with ASD, may be associated with hyperarousal conditions with cognitive hypersensitivity, misattribution of negative experiences, and the perceptual thinking style. Together with the emerging new genetic concepts concerning human behavioral complex traits, the results and constructions of these recent studies may further warrant that reconsideration of the relationship between ASD and psychotic conditions is necessary. In addition, the possibility that psychotic conditions are the secondary derivative states in individuals with ASD or in individuals with subclinical ASD components should be constructively examined.

Biomarkers for early diagnosis of autism obtained through bioinformatics analysis of human blood sample

Objective:autism spectrum disorder(ASD),a serious disorder that begins early in life,con-tinues throughout the lifespan.Children with ASD who are diagnosed early are more responsive to therapeutic interventions and have less social and language impair-ment than children diagnosed later;however,current di-agnostic measures are mostly applied to children older than one year and lack the appropriate biological markers for early diagnosis of ASD.Using bioinformatic analy-sis,this study explores the molecular information mech-anism of ASD.Method:in this study,we used dataset GSE6575 from Gene Expression Omnibus(GEO)to an-alyze the mRNA expression profile of ASD,including 35 ASD samples and 12 normal control samples looking for different genes and we did enrichment analysis of those genes.We then used the STRING database to construct a protein-protein interaction(PPI)network of differential genes.Finally,Cytoscape plug-in cytoHubba was used to search for hub genes.The diagnostic value of the hub genes was verified by subject operating characteristic curves.Result:we looked for 50 different genes and did an enrichment analysis of those genes.The results of the enrichment analysis showed that these differential genes were mainly concentrated in the response to viruses,the immune regulation of inflammation and energy metabo-lism.Using Cytoscape plug-in cytoHubba,we found ten different genes.We drew ROC curves for all ten genes among which two genes,interleukin 2 receptor subunit beta(IL2Rβ)and perforin 1(PRF1),had good sensitivity and specificity for the early diagnosis of autism.The ar-eas under the ROC curves were 0.855,0.830 for IL2Rβ,PRF1.Conclusion:data analysis using the GEO data-base can provide new insights into the etiology of ASD as well as some possible biomarkers and therapeutic targets for early diagnosis and treatment of ASD.

Effects of COVID-19 on children with autism

The coronavirus disease 2019(COVID-19)pandemic affects all countries and populations worldwide,significantly impacting people with autism with a high risk of morbidity and mortality due to COVID-19.Approximately 25%of children with autism have an asymptomatic or symptomatic immune deficiency or dysfunction.In addition,they frequently have various comorbid conditions that increase the severity of COVID-19.In addition,severe COVID-19 during pregnancy may increase the risk of autism in the offspring.Furthermore,severe acute respiratory syndrome coronavirus 2 could target human nervous system tissues due to its neurotrophic effects.The COVID-19 pandemic intensely impacts many patients and families in the autism community,especially the complex management of autism-associated disorders during the complete lockdown.During the complete lockdown,children with autism had difficulties coping with the change in their routine,lack of access to special education services,limited physical space available,and problems related to food and sleep.Additionally,children with autism or intellectual disabilities are more liable to be abused by others during the pandemic when the standard community supports are no longer functioning to protect them.Early detection and vaccination of children with autism against COVID-19 are highly indicated.They should be prioritized for testing,vaccination,and proper management of COVID-19 and other infectious diseases.In this review,we discuss the various effects of COVID-19 on children with autism,the difficulties they face,the increased risk of infection during pregnancy,how to alleviate the impact of COVID-19,and how to correct the inequalities in children with autism.

娄必丹基于“心脑同治”治疗ASD认知障碍的选穴思路

娄必丹教授认为,神志疾病主要责之心脑,心脑功能失常则是孤独症谱系障碍(autism spectrum disorders,ASD)患儿认知障碍的主要病机。目前,临床治疗ASD多单纯选用头针,娄教授基于“心脑同治”理论,提出宁心调神针刺方法。该针刺方法选用心经之神门、通里、少海及心包经之内关、大陵以宁心调神,聪脑益智,头部选用督脉之百会、印堂、神庭,配合经外奇穴四神聪和本神穴(与神庭穴组合为“智三针”穴组)以通督调神、醒神益智。

Pre-autism:Advancing early identification and intervention in autism

Autism spectrum disorder(ASD)is often diagnosed long after symptoms have become noticeable.This delay can make it difficult to provide early intervention,which can impact long-term outcomes.The concept of"pre-autism"highlights the phase before a formal diagnosis of ASD,providing an opportunity for earlier identification and intervention,which could be a turning point in ASD management.In a previous article,we explored different ways of diagnosing pre-autism,including historical records,physical markers,laboratory tests,and radiological evidence.This manuscript builds on that foundation by emphasizing the importance of early diagnosis and intervention in ASD.Recent research advancements have clarified that ASD presentations can be complex,and individualized support strategies are necessary.The significance of pre-autism lies in its potential to alter the trajectory of ASD through early detection and intervention despite challenges such as limited awareness and variability in symptom presentation.Biomarkers and diagnostic tools have shown promise as avenues for early detection,but it is essential to exercise caution and not rely too heavily on yet-tobe-established markers.Addressing these challenges requires a collaborative effort to increase awareness,improve access to diagnostic tools,and foster inclusive environments.Ultimately,this manuscript calls for ongoing research,advocacy,and resource allocation to enhance early detection and intervention efforts,ensuring optimal outcomes for individuals on the autism spectrum.

Sex Differences in Diagnosis and Clinical Phenotypes of Chinese Children with Autism Spectrum Disorder

The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder（ASD） in China＇s mainland. Children diagnosed with ASD（n = 1064, 228 females） were retrospectively included in the analysis. All children were assessed using the Autism Diagnostic Interview-Revised（ADI-R） and Autism Diagnostic Observation Schedule（ADOS）. The results showed that girls scored significantly higher in ADI-R socioemotional reciprocity than boys, and also scored lower in ADI-R and ADOS restricted and repetitive behaviors（RRBs）. Meanwhile, the proportions of girls who satisfied the diagnostic cut-off scores in the ADI-R RRBs domain were lower than in boys（P ／ 0.05）. Our results indicated that girls with ASD show greater socio-emotional reciprocity than boys. Girls also tended to show fewer RRBs than boys, and the type of RRBs in girls differ from those in boys. The ADI-R was found to be less sensitive in girls, particularly for assessment in the RRBs domain.

ASD儿童父母的亲职压力及心理影响因素研究

目的探讨孤独症谱系障碍（ASD）儿童父母的亲职压力及心理影响因素。方法选取2014至2015年由福建省福州儿童医院心理科和福建医科大学附属协和医院儿童神经专科高年资主治以上医师确诊、并其父母完成问卷调查的ASD儿童134例,采用亲职压力指标简表（包括父母困扰、亲子失功能及困难儿童3个分量表）、一般自我效能感量表、特质应对方式问卷对134名ASD儿童父母（实验组）进行调查,同时对115名正常儿童父母（对照组）施测,对结果进行分析。结果实验组亲职压力总分及各维度得分均高于对照组（t=8.40～9.95,P〈0.05）;实验组一般自我效能感低于对照组（t=-6.61,P〈0.05）,且采用更多的消极应对方式和更少的积极应对方式（t值分别为6.39、-4.72,P〈0.05）。相关分析显示：ASD儿童父母的亲职压力与消极应对呈正相关（r=0.328,P〈0.01）,ASD儿童父母的亲职压力总分、父母困扰及困难儿童得分与患儿父母一般自我效能感均呈负相关（r值分别为-0.222、-0.251、-0.177,P〈0.05）。结论 ASD儿童父母普遍存在较高水平的亲职压力,其亲职压力与家长的一般自我效能感及消极应对方式有关。

ASD患儿脑扣带回代谢物浓度与临床特征的相关性

目的探讨学龄前期孤独症谱系障碍(ASD)患儿脑扣带回代谢物定量及其与临床特征的相关性。方法选取2016年1月至2018年12月在丽水市中心医院就诊的32例学龄前期ASD患儿(病例组)和25例学龄前期体检健康儿童(对照组),均行磁共振波谱学扫描,比较两组儿童不同脑区各代谢物浓度的差异,并采用Pearson相关性分析对病例组患儿不同脑区代谢物浓度与各相关量表评分的关系进行研究。结果病例组患儿前部中扣带回皮层、前扣带回皮层和后扣带回皮层脑区N-乙酰天门冬氨酸(NAA)浓度均显著低于对照组(t值分别为2.60、3.71、3.15,均P<0.05);病例组患儿后扣带回皮层脑区谷氨酸复合物(Glx)和胆碱浓度均显著低于对照组(t值分别为2.43、3.55,均P<0.05)。经Pearson相关性分析显示,后扣带回脑区NAA代谢物浓度与儿童孤独症评定量表存在负相关关系(r=-0.56,P<0.01)。结论学龄前期ASD患儿的脑扣带回生化代谢物浓度异常改变,且后扣带回脑区NAA代谢物浓度与儿童孤独症评定量表评分呈负相关关系,可为ASD提供一种临床无创性辅助诊断方法。

核磁定量参数联合听性脑干反应对ASD的诊断价值

目的:探讨磁共振弥散张量成像(DTI)联合听性脑干反应对孤独症谱系障碍(ASD)的诊断价值。方法:选取2019年1月—2022年1月就诊的ASD患儿60例(观察组),其中轻中度患儿40例,重度患儿20例,同时选取正常儿童60名作为对照组,分析DTI参数各向异性分数(FA)、表观扩散系数(ADC)及脑干听觉诱发电位(BAEP)参数差异。结果:观察组胼胝体压部FA明显高于对照组(t=6.433,P<0.05),而ADC明显低于对照组(t=8.468,P<0.05)。观察组Ⅰ波潜伏期较对照组缩短(t=3.417,P<0.05)。观察组重度患儿胼胝体压部FA明显高于轻中度患儿(t=2.457,P<0.05),而胼胝体压部ADC和Ⅰ波潜伏期明显低于轻中度患儿(t=4.564,P<0.001;t=3.519,P<0.05)。胼胝体压部FA、胼胝体压部ADC和Ⅰ波潜伏期预测重度ASD的受试者工作特征(ROC)曲线下面积分别为0.667、0.789和0.700(均P<0.05)。结论:核磁定量参数联合听性脑干反应在ASD的诊断和患儿疾病严重程度鉴别中具有一定的价值。

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).

An Overview of Autism Spectrum Disorder, Heterogeneity and Treatment Options

Since the documented observations of Kanner in1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder（ASD）.Re？ecting this complicated history, there has been continual re？nement from DSM-III with ‘Infantile Autism＇ to the current DSM-V diagnosis. The disorder is now widely accepted as a complex, pervasive, heterogeneous condition with multiple etiologies, sub-types, and developmental trajectories. Diagnosis remains based on observation of atypical behaviors, with criteria of persistent de？cits in social communication and restricted and repetitive patterns of behavior. This review provides a broad overview of the history, prevalence, etiology, clinical presentation, and heterogeneity of ASD. Factors contributing to heterogeneity, including genetic variability, comorbidity, and gender are reviewed. We then explore current evidencebased pharmacological and behavioral treatments for ASD and highlight the complexities of conducting clinical trials that evaluate therapeutic ef？cacy in ASD populations.Finally, we discuss the potential of a new wave of research examining objective biomarkers to facilitate the evaluation of sub-typing, diagnosis, and treatment response in ASD.

Evidence of neurodegeneration in autism spectrum disorder

Autism spectrum disorder(ASD)is a neurological disorder in which a significant number of children experience a developmental regression characterized by a loss of previously-acquired skills and abilities.Loss of neurological function in ASD,as observed in affected children who have regressed,can be explained as neurodegeneration.Although there is research evidence of neurodegeneration or progressive encephalopathy in ASD,the issue of neurodegeneration in ASD is still under debate.Evidence of neurodegeneration in the brain in ASD includes:(1)neuronal cell loss,(2)activated microglia and astrocytes,(3)proinflammatory cytokines,(4)oxidative stress,and(5)elevated 8-oxo-guanosine levels.The evidence from this review suggests that neurodegeneration underlies the loss of neurological function in children with ASD who have experienced regression and loss of previously acquired skills and abilities,and that research into treatments to address the issue of neurodegeneration in ASD are warranted.

Differential diagnosis between autism spectrum disorder and other developmental disorders with emphasis on the preschool period

Background Neurodevelopmental disorders are a heterogeneous group of conditions that manifest as delays or deviations in the acquisition of expected developmental milestones and behavioral changes.Autism spectrum disorder(ASD)is a neurodevelopmental disorder characterized by deficits in communication and social interaction and by repetitive and restricted patterns of behavior,interests and activities.The aim of this review is to discuss the clinical features of the differential diagnoses of ASD that are prevalent among preschoolers,focusing on their similarities and disparities.Data sources The international medical literature search was conducted using PubMed and was revised regarding the subject using single and/or combined keywords as follows:differential diagnosis,preschoolers,diagnostic challenge,attention deficit hyperactivity disorder,intellectual disability,high abilities/giftedness,childhood apraxia of speech,social communication disorder,Landau–Kleffner syndrome,stereotyped movement disorder and excessive screen time.Results We describe conditions commonly found in clinical practice,taking ASD as a reference.We addressed converging and divergent aspects of behavior,cognition,communication,language,speech,socialization,and stereotypes for the diagnosis of ASD and other disorders identified as potential differential or comorbid diagnoses.Conclusions The ranking and characterization of symptoms appear to be essential for better understanding the underlying common ground between children with developmental disorders and children with ASD,thus properly diagnosing and directing social,professional,or medication interventions.This detailed discussion adds to the literature since,although ASD differential diagnoses are frequently mentioned and discussed in textbooks and journal articles,they rarely occupy a prominent place as we aimed herein.