Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

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.

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.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

Research on the Effect of Dance Therapy on Improving Social Communication Ability of Children with Autism

Research motivation:Through the 12 weeks dance therapy intervention for children with autism,the purpose is to explore the intervention model of dance therapy for children with autism and the changes in motor ability,social ability,and communication ability of children with autism after dance therapy intervention.The results of the research are expected to expand the intervention mode of dance therapy in my country and provide practical reference for rehabilitation intervention of children with autism.Research methods:24 autistic boys aged 6 to 12 with mild to moderate symptoms were recruited and screened through the Internet as the subjects of this study.We randomly divided them into experimental group(N=12)and control group(N=12).All children with autism have an autism diagnosis certificate issued by Children’s Hospital or a tertiary hospital,excluding other mental diseases(such as epilepsy,major physical disability,mental illness,no history of drugs and other interventions,etc.).We used the paired sample t-test to compare the score difference between the dance treatment group and the control group before and after the two groups,and used the observation method to record the basic communication behavior and the number of active communication behaviors in the experimental group during the intervention process.All data analysis is used in SPSS 20.0.Research results:After 12 weeks of dance therapy intervention,there were statistically significant differences in the gross movement,balance,and coordination abilities of the children in the experimental group compared with those before the intervention(p<0.01).There was no significant difference between the children in the control group(p>0.05).After 12 weeks of dance therapy intervention,there were statistically significant differences in the scores of the social response scale for children with autism in the experimental group(p<0.05).There was no significant change in the scores of each item of the SRS scale before and after intervention in the control group and the dance treatment group(p>0.05).

Gastrointestinal problems in a valproic acid-induced rat model of autism: From maternal intestinal health to offspring intestinal function

BACKGROUND Autism spectrum disorder(ASD)is a developmental disorder characterized by social deficits and repetitive behavior.Gastrointestinal(GI)problems,such as constipation,diarrhea,and inflammatory bowel disease,commonly occur in patients with ASD.Previously,GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission.AIM To explore whether GI problems in ASD are related to maternal intestinal inflam-mation and gut microbiota abnormalities.METHODS An ASD rat model was developed using valproic acid(VPA).Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes.RESULTS VPA exposure during pregnancy led to pathological maternal intestinal changes,resulting in alterations in maternal gut microbiota.Additionally,the levels of inflammatory factors also increased.Moreover,prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of infla-mmatory factors.CONCLUSION GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality.Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIM To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.METHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of P<0.001.The test group also significantly increased their consumption of whole and/or organic foods with a pre-intervention diet score of 100(mean=5.882,SD=2.472)and post-intervention diet score of 121(mean=7.118,SD=2.390)and the paired t-test analysis showing a significance of P<0.05.CONCLUSION Here we show nutritional epigenetics education can be used to reduce ultra-processed food intake and improve attitude among parents having learning-disabled children with autism or ADHD.

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.

From Signals to Solutions: Exploring Early Detection of Neuropsychiatric and Neurodevelopment Disorders through Biomarkers

In 2013, the percentage of children ranging from 5 to 17 years who reported being diagnosed with autism surged to 1.2% from 0.1% in 1997 [1]. Alongside this increase in the incidence of autism in children, there were findings of a 21% increase in children who displayed behavioral and conduct problems from 2019 to 2020 [2]. Early detection of neuropsychiatric and neurodevelopmental disorders in children is critical for timely intervention and improved long-term outcomes. With early intervention, there is better aptitude to support healthy development and give proper treatment to attain a better quality of life. This paper explores studies aimed at enhancing the early detection of these disorders through the use of biomarkers with the aim of creating a bridge between the worlds of research and clinical practice. The disorders in this paper specifically discussed are Major Depressive Disorder, Bipolar Disorder, and Autism Spectrum Disorder. With this bridge, we can foster collaborations and encourage further advancement in the field of early detection and intervention.

Evaluation of Clinician Training in Autism Screening, Care Management, and Patient Education

Objective: The demand for pediatric developmental evaluations has far exceeded the workforce available to perform them, which creates long significant wait times for services. A year-long clinician training using the Extension for Community Healthcare Outcomes (ECHO®) model with monthly meetings was conducted and evaluated for its impact on primary care clinicians’ self-reported self-efficacy, ability to administer autism screening and counsel families, professional fulfillment, and burnout. Methods: Participants represented six community health centers and a hospital-based practice. Data collection was informed by participant feedback and the Normalization Process Theory via online surveys and focus groups/interviews. Twelve virtual monthly trainings were delivered between November 2020 and October 2021. Results: 30 clinicians participated in data collection. Matched analyses (n = 9) indicated statistically significant increase in self-rated ability to counsel families about autism (Pre-test Mean = 3.00, Post-test Mean = 3.89, p = 0.0313), manage autistic patients’ care (Pre-test Mean = 2.56, Post-test Mean = 4.11, p = 0.0078), empathy toward patients (Pre-test Mean = 2.11, Post-test Mean = 1.22, p = 0.0156) and colleagues (Pre-test Mean = 2.33, Post-test Mean = 1.22, respectively, p = 0.0391). Unmatched analysis revealed increases in participants confident about educating patients about autism (70.59%, post-test n = 12 vs. 3.33%, pre-test n = 1, p = 0.0019). Focus groups found increased confidence in using the term “autism”. Conclusion: Participants reported increases in ability and confidence to care for autistic patients, as well as empathy toward patients and colleagues. Future research should explore long-term outcomes in participants’ knowledge retention, confidence in practice, and improvements to autism evaluations and care.

Metabolomic changes in children with autism

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

Decoding the genetic landscape of autism:A comprehensive review

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for individuals affected by ASD.

Glyphosate Exposure Associated with Human Neurodegenerative Disorders: A Scoping Review

Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.

Faith and Belief in Autism in Cote d’Ivoire: About Judith, God’s Strange Gift

Faced with autism, motherhood and parenthood are turned upside down in many ways. Coping with stress and mental health problems, continuing to assume a rewarding parental role and finding suitable care are the trials and tribulations that mark out the journey of African parents. Faith and belief have been described as providing meaning and coping mechanisms in the frightening ordeal of disability. An encounter with a young girl and her parents provided an opportunity to analyse the mother’s experience and the impact of beliefs and discourses on her commitment to care. Based on this clinical story, we discuss the place of other-actors (parents and carers) and the Other-God in relation to the psychopathological dynamics of the mother.

Early Intervention Facilitates Neuropsychological Development in Children with Autism and Attention Deficit Hyperactivity Disorder

Objective:This study aims to investigate the impact of early intervention on neuropsychological development in children with autism and attention deficit hyperactivity disorder(ADHD),providing effective intervention strategies for clinical practice.Methods:A total of 130 children with autism and ADHD who visited the hospital between June 2023 and June 2024 were selected as study subjects and randomly divided into an intervention group and a control group,with 65 children in each group.The intervention group received a one-year early comprehensive intervention,including behavioral therapy,cognitive training,and family guidance,while the control group only received routine medical care.The neuropsychological development assessment scale was used to evaluate both groups before and after the intervention to compare changes in their neuropsychological development levels.Results:Children in the intervention group showed significant improvements in cognitive function,social skills,language ability,and attention concentration,with an average improvement score of 23.5 points.Children in the control group did not show significant improvements in these areas,with an average improvement score of only 5.8 points.The difference between the two groups was statistically significant(P<0.05).Conclusion:Early comprehensive intervention has a significant promoting effect on the neuropsychological development of children with autism and ADHD.Targeted behavioral therapy,cognitive training,and family guidance can effectively enhance children’s cognitive,social,language,and attention abilities,laying a solid foundation for their future overall development.Therefore,it is recommended to actively promote and apply early intervention strategies in clinical practice.

Play therapy in children with autism:Its role,implications,and limitations

Play is a pleasurable physical or mental activity that enhances the child’s skills involving negotiation abilities,problem-solving,manual dexterity,sharing,decision-making,and working in a group.Play affects all the brain's areas,structures,and functions.Children with autism have adaptive behavior,adaptive response,and social interaction limitations.This review explores the different applications of play therapy in helping children with autism disorder.Play is usually significantly impaired in children with autism.Play therapy is mainly intended to help children to honor their unique mental abilities and developmental levels.The main aim of play therapy is to prevent or solve psychosocial difficulties and achieve optimal child-healthy growth and development.Play therapy helps children with autism to engage in play activities of their interest and choice to express themselves in the most comfortable ways.It changes their way of self-expression from unwanted behaviors to more non-injurious expressive behavior using toys or activities of their choice as their words.Play therapy also helps those children to experience feeling out various interaction styles.Every child with autism is unique and responds differently.Therefore,different types of intervention,like play therapy,could fit the differences in children with autism.Proper evaluation of the child is mandatory to evaluate which type fits the child more than the others.This narrative review revised the different types of play therapy that could fit children with autism in an evidence-based way.Despite weak evidence,play therapy still has potential benefits for patients and their families.

Pharmacotherapy in autism spectrum disorders,including promising older drugs warranting trials

Available pharmacotherapies for autism spectrum disorders(ASD)are reviewed based on clinical and research experience,highlighting some older drugs with emerging evidence.Several medications show efficacy in ASD,though controlled studies in ASD are largely lacking.Only risperidone and aripiprazole have Federal Drug Administration approval in the United States.Methylphenidate(MPH)studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder(ADHD)than in the typically developing(TD)population;atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes.Guanfacine improved hyperactivity in ASD comparably to TD.Dextroamphetamine promises greater efficacy than MPH in ASD.ADHD medications reduce impulsive aggression in youth,and may also be key for this in adults.Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors.Trials of antiseizure medications in ASD remain inconclusive,however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors.No identified drugs treat ASD core symptoms;oxytocin lacked efficacy.Amitriptyline and loxapine however,show promise.Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies,but may be weight-sparing.Amitriptyline at approximately 1 mg/kg/day used cautiously,shows efficacy for sleep,anxiety,impulsivity and ADHD,repetitive behaviors,and enuresis.Both drugs have promising neurotrophic properties.

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.