Therapy For Autism Spectrum Disorder Research Articles

Autism Spectrum Disorder Model Mice Induced by Prenatal Exposure to Valproic Acid Exhibit Enhanced Empathy-Like Behavior via Oxytocinergic Signaling.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms, including impairments in social behavior and repetitive interests. Recent studies have revealed that individuals with ASD also display decreased empathy, ultimately leading to difficulties in social relationships; however, another report indicated that individuals with ASD have enhanced emotional empathy. Nonetheless, the neurobiological mechanisms underlying altered empathy in individuals with ASD remain unclear. In this study, we assessed empathy-like behaviors in valproic acid (VPA)-treated mice-a mouse model of ASD with observational fear learning. We then investigated the brain regions and signaling systems responsible for the altered empathy-like behaviors in VPA-treated mice. As a result, mice prenatally exposed to VPA displayed increased empathy-like behaviors, which were not attributed to altered sensitivity to auditory stimuli or enhanced memory for pain-related contexts. Immunohistochemical analysis revealed that the number of c-Fos positive oxytocinergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was significantly higher in VPA-treated mice after observational fear learning. Finally, we found that pretreatment with L-368899, an antagonist of the oxytocin receptor, repressed the empathetic behavior in VPA-treated mice. These results suggest that VPA-treated ASD model animals showed increased emotional empathy-like behaviors through the hyperactivation of PVN oxytocinergic neurons for the first time. Further investigation of this hyperactivity will help to identify extrinsic stimuli and the condition which are capable of activation of PVN oxytocinergic neurons and to identify novel approach to enhance oxytocin signaling, which ultimately pave the way to development of novel therapy for ASD.

Profiling plasma levels of thiamine and histamine in Jordanian children with autism spectrum disorder (ASD): potential biomarkers for evaluation of ASD therapies and diet

ABSTRACT Background: The current work involved monitoring two biomarkers in the plasma of children with ASD: the cofactor thiamine that is involved in neurotransmitters modulation for acetylcholine, and the compound histamine, which acts as a neuromodulator by regulating the release of other neurotransmitters. This is the first report to highlight the potential utilization of plasma levels of the selected two brain-related biomarkers in children with ASD. Methods: A total of 43 children with ASD of both genders (age 4–12 years) were involved in this study and compared to age and gender-matched control children (n = 42). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5), followed by an additional assessment using the Childhood Autism Rating Scale (CARS). All participants were Jordanian children on Mediterranean diet, and had no history of chronic illness or medications. Measurement of thiamine and histamine in plasma was performed using enzyme-linked immunosorbent assay (ELISA). Results: The outcomes revealed that average histamine levels (31.7 ± 18.5 ng/ml) of ASD group were 5.3× higher (p < .001) compared to their control (0.013 ± 0.011 ng/ml; 6.03 ± 4.25 ng/ml), while thiamine (10.78 ± 7.49 ng/ml) levels of ASD group were significantly lower (p < .001) than the control (37.92 ± 26.87 ng/ml; 0.209 ± 0.054 ng/ml). Conclusions: The study is proposing that monitoring of the plasma levels of thiamine and histamine as biomarkers for future evaluation and development of ASD therapies and nutritious diets.

Sharing Worlds: Design of a Real-Time Attention Classifier for Robotic Therapy of ASD Children.

Joint attention is the capacity of sharing attention between two agents and an aspect of the environment, through the use of different cues, namely gaze. This capacity is of paramount importance for social skills. People with Autism Spectrum Disorder (ASD) present certain deficits in joint attention. Therefore, there is an increasing interest in finding therapies to improve this skill. Some of these therapies include robots since they are known to be attractive to people with autism due to their motivation ability and predictability when compared with humans. In this line, we have designed a real-time attention classifier for a triadic robotic therapy, using Gaze360 and geometrical considerations of the scene. We were able to classify the gaze of the therapist and the one of the child during the whole session, even in a highly unconstrained scenario with a single camera, achieving a mean accuracy of 59%. This classifier can be used for the measurement of joint attention, an important metric for the development of adaptive robotic therapies, where increasing levels of difficulty and engagement are provided dependent on the ASD children, who are characterised by high heterogeneity. Future work will pass by the calculation of this metric and integration on a robotic platform for ASD therapy to understand the impact of these robotic therapies in improving ASD symptoms, specifically on how ASD children share their attention with other people present in the rehabilitation scenarios.

CRISPR-mediated activation of autism gene Itgb3 restores cortical network excitability via mGluR5 signaling

Many mutations in autism spectrum disorder (ASD) affect a single allele, indicating a key role for gene dosage in ASD susceptibility. Recently, haplo-insufficiency of ITGB3, the gene encoding the extracellular matrix receptor β3 integrin, was associated with ASD. Accordingly, Itgb3 knockout (KO) mice exhibit autism-like phenotypes. The pathophysiological mechanisms of Itgb3 remain, however, unknown, and the potential of targeting this gene for developing ASD therapies uninvestigated. By combining molecular, biochemical, imaging, and pharmacological analyses, we establish that Itgb3 haplo-insufficiency impairs cortical network excitability by promoting extra-synaptic over synaptic signaling of the metabotropic glutamate receptor mGluR5, which is similarly dysregulated in fragile X syndrome, the most frequent monogenic form of ASD. To assess the therapeutic potential of regulating Itgb3 gene dosage, we implemented CRISPR activation and compared its efficacy with that of a pharmacological rescue strategy for fragile X syndrome. Correction of neuronal Itgb3 haplo-insufficiency by CRISPR activation rebalanced network excitability as effectively as blockade of mGluR5 with the selective antagonist MPEP. Our findings reveal an unexpected functional interaction between two ASD genes, thereby validating the pathogenicity of ITGB3 haplo-insufficiency. Further, they pave the way for exploiting CRISPR activation as gene therapy for normalizing gene dosage and network excitability in ASD.

Sensory and Motor Difficulties in Autism

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interaction and communication, and by restricted and repetitive behaviors. A meta-analysis describes motor difficulties in ASD (Downey and Rapport, 2012) in 85% to 90% of cases (Liu et al. 2010). Electronic devices will help to better characterize these movement impairments (Gargot et al., in press). Another meta-analysis shows difficulties in sensorial integration in ASD, with a prevalence ranging from 45 to 95% (Ben Sasson, 2009). Sensorimotor contigencies are learned interactively (Jacquey et al., 2020), in a perception-action loop, an early milestone in development (Piaget, 1937). A cascade model (Bonnet-Brilhault, 2017) hypothesizes that social difficulties stem in sensorimotor difficulties (Cook, 2016; Neal, 2011; Dziuk et al. 2007; Kojovic, 2019), themselves atypically developed due to a peculiar neurobiological background. This model predicts that early sensorimotor reeducation could prevent the development of social difficulties, whereas the rehabilitation of social skills would improve only part of the impairment, that is driven by sensorimotor processes. How to target these issues? Grandin, 1992 and Edelson et al., 1999 validated the efficacy of deep pressure therapy in ASD. It is important to improve attractivity and decrease the stigmatization of this method. Oto is a compressive armchair with inflatable cushions controlled electronically. It records level of pressure and its duration, chosen by the user. A systematic review showed the efficacy of virtual reality in ASD (Mesa-Gresa et al, 2018). A CAVE device could habituate children to ecological audio-visual stimulations.DisclosureThomas Gargot was paid by the French ministry of research (Doctoral school), French ministry of health (médaille d’argent, CCA-AHU) for a PhD and CCA position. During his PhD, he prepared several scientific presentations with Dr Asselborn. This work led

Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Autistic-Like Behaviors of SHANK3 Mutant Beagle Dogs.

Mesenchymal stem cell-based therapy has emerged as a great potential approach to treat individuals with autism spectrum disorders (ASD), a group of developmental disabilities characterized by impairments in social interaction and communication. Stem cells from human exfoliated deciduous teeth (SHED), holding earlier developing characteristics, have immune-modulatory and anti-inflammatory properties. To investigate whether SHED transplantation can rescue autistic-like symptoms in SHANK3 mutant beagle dogs, 12 SHANK3 mutant beagle dogs were randomly assigned into 2 groups according to their behavior evaluated by social interaction tests. Six mutant dogs received 6 intravenous infusions of SHED and were followed up for 3 months by testing social interaction and inflammatory cytokine levels. We found that infusion of SHED significantly improved impaired social novel preference of SHANK3 mutant beagle dogs at 1- and 3-month follow-ups. Social intimacies (following, sniffing, and licking) between mutant beagle dogs and human experimenters were partly improved. Stressed tail posture, indicating social stress, was also significantly alleviated. In addition, we showed that the levels of serum interferon-γ and interleukin-10 were notably increased and decreased, respectively, in SHANK3 mutant beagle dogs. Infusion of SHED was able to rescue altered interferon-γ and interleukin-10 levels. We failed to observe any serious adverse events after infusion of SHED. In summary, SHED transplantation may be a safe and effective therapy for ASD. The correction in the levels of serum interferon-γ and interleukin-10 may serve as an index to predict autistic severity and therapeutic outcomes.

Development of Discrete Trial Training (DTT) Procedure in Smart Applied Behavior Analysis (Smart ABA) for Autism

Lovaas was the first professional to use the principle of behavior modification for autism with a technique he called DTT (Discrete Trial Training), which later to be known as ABA (Applied Behavior Analysis). Through his study, Lovaas found that 47% of subjects had excellent results. While 42% with varying degrees, and the other 11% of subjects very little progress. In DTT, there are 2 possible responses, but the researchers' observations do not seem to be just 2 possibilities. This study's goal is to improve discrete trial training (DTT) procedures to increase the effectiveness of Smart Applied Behavior Analysis therapy for autism spectrum disorder. This study uses quantitative methods with a literature review research design. Research data is obtained through interviews, document studies, and literature reviews (journals and websites). The study focused on the researchers' findings that were adapted to earlier theories. The study was conducted at the researchers' autism clinic. During the implementation of therapy using DTT, the researchers observed that the child's response is not only 2, namely correct and incorrect. Based on the study conducted, it was obtained that there were 5 possible responses: Correct, incorrect, partial-correct, off-task, and no-response. Each of which required different feedback and its subsequent sequences, as well as the possibility of different causative factors which require different interventions. Further research with large and multi-center samples will further increase the effectiveness of DTT applications in Smart ABA for autism. This study was based on the researchers' findings while observing, mentoring, and supervising autism therapists.

An Evaluation of Animal-Assisted Therapy for Autism Spectrum Disorders: Therapist and Parent Perspectives.

Although there are a variety of psychological and therapeutic approaches to coping Autism Spectrum Disorder, people with autism still face some challenges in a “normal” therapy setting. Some therapy organizations and services have proposed an alternative therapy approach, Animal-assisted therapy (AAT). The aim of this phenomenological study was to gain a better understanding of the therapists and parents of individuals who choose the alternative approach, AAT. Data were collected through structured interviews with a group of three therapists and four parents. An analysis of the data revealed three main themes; the first theme named the perceived benefits of AAT with three subthemes consisting of physical benefits, sensory benefits and emotional benefits. The second theme is named the way AAT works with subthemes of client-centred therapy and mixed models, and the third theme is potential limitations of AAT. Limitations and suggestions for future research are discussed.

Nonpharmaceutical therapy for autism spectrum disorder: A protocol for systematic review and network meta-analysis.

Background:Autism spectrum disorder (ASD) is a widespread developmental disorder of the nervous system with an unclear etiology and pathogenesis. Its global incidence is currently increasing, and no effective drugs are available to improve its core symptoms. Nonpharmaceutical therapy can effectively relieve the core symptoms of autism, has fewer side effects than drugs, and is easily accepted by patients. This systematic and network meta-analysis aimed to evaluate the impact of non-pharmaceutical therapy on autism to explore preferable therapeutic options for autism.Methods:Online databases, including the China National Knowledge Infrastructure [CNKI], SinoMed, Wanfang Database [WF], China Science and Technology Journal Database [VIP], MEDLINE, Web of Science, EMBASE, and the Cochrane Library will be searched for randomized controlled trials of nonpharmacological interventions for autism published before October 2021. Two researchers will be independently responsible for the literature screening, data extraction, and quality assessment. Standard paired and Bayesian network meta-analyses will be performed using RevMan 5.3 Software and GEMTC 0.14.3, to compare the efficacy and safety of different nonpharmacological regimens.Results:The results of this systematic and network meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This study provides a comprehensive and reliable evidence-based reference for the efficacy and safety of different non-pharmacological interventions for autism.PROSPERO registration number:CRD 42021275571

Future perspectives on cell therapy for autism spectrum disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication, abnormal to absent verbal communication, the presence of repetitive stereotypic verbal and non-verbal behaviors and restricted interests, with onset early in life. We showed cognitive and behavioral characteristics of ASD by impairment of communication, cognition, perception, motor skills, executive function, theory of mind and emotion control. Recently, pathogenesis of immune pathology in the brains of individuals with ASD has been focused. New therapeutic approaches in the viewpoints of immune modulation and microglial function are logical for novel treatments for individuals with ASD. Cell therapies such as umbilical cord blood cells and mesenchymal stromal cells for ASD will be a challenging and encouraging field in the future clinical study with progress of biotechnological science.

Applied-behavioural analysis therapy for autism spectrum disorder students through virtual reality

Applied-behavioural analysis therapy for autism spectrum disorder students through virtual reality

Autism Spectrum Disorder Therapy: Analysis of Artificial Intelligence integrated Robotic Approach

Autism Spectrum Disorder is a developmental disorder that may manifest in a myriad of ways such as difficulties in social interaction and a tendency to engage in repetitive patterns of behaviour. Over the years, several kinds of treatment protocols have been proposed and implemented. One such area that is attracting the attention of researchers in the field is a robot-based approach in the treatment of children diagnosed with the disorder. Here we propose a viable method via the integration of apex technological methods like Artificial Intelligence, Machine Learning and Medical Robotics, coupling it with problem specific algorithms in OpenCV along with principles of Applied Behavioural Analysis to help possibly alleviate a key symptom displayed by children in terms of level of social interaction - that of eye-contact. This would be achieved via an AI-integrated Robotic Framework. The project also considers the possibility of inclusion of the growing research field of Quantum Computing to realize the process and investigates its viability as a potential source of innovation in the future.

Algorithmic Approaches to Classify Autism Spectrum Disorders: A Research Perspective

Autism Spectrum Disorder (ASD) is a neurodevelopmental disability that exhibits sluggish progress in vocal development, restricted interest in normal activity and repetitive disoriented behavior. This syndrome, has gained a lot of attention due to its prevalence among children across all countries and from different economic backgrounds. However, ASD detection and treatment yet remains in its infancy due to the lack of awareness among parents, limited screening of proper developmental milestones and a dearth of diagnostic tools to classify this syndrome with convincing accuracy. Recent studies report that scalable biomarkers for early detection have made little progress in research due to the erraticism of this disorder. Moreover, the study on developing tools or applications for parents, teachers, and healthcare workers to identify children who exhibit any form of autism is still a work in progress. The research work undertaken in this paper presents an analysis of supervised machine learning algorithms on mining interesting details that link the diverse nature of ASD and the possibility of computationally detecting markers for the syndrome. The preliminary findings on the performance of traditional machine learning algorithms in ASD classification is reported with the possibility of integrating deep learning architectures for ASD detection and therapy.

Sex-specific differences in the gut microbiota and fecal metabolites in an adolescent valproic acid-induced rat autism model.

Alterations in the microbiota-gut-brain axis are associated with the onset of autism spectrum disorder (ASD). Numerous studies have reported that the gut microbiota (GM) is significantly altered in individuals with ASD and animal models of ASD. However, few studies have focused on sex-specific differences in the GM and fecal metabolites of ASD. In this study, we performed 16S rRNA gene sequencing and untargeted metabolomics in parallel on fecal samples from a valproic acid (VPA)-induced rat model of autism (VPA rats). Based on these data, we analyzed differentially abundant metabolites in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to reveal the possible mechanism of ASD. Data derived from male and female rats were analyzed separately. Finally, we analyzed the correlation between characteristic genera and characteristic fecal metabolites in VPA rats of both sexes. The results showed that VPA rats of both sexes presented remarkable alterations in the GM and fecal metabolites. Sex-specific differences were noticeably detected. We identified 51 annotated differentially abundant fecal metabolites and 1 differentially enriched KEGG pathway between the male VPA and male control groups. Ruminococcus_2, Candidatus_Soleaferrea, Desulfovibrio, Candidatus_Saccharimonas, Intestinimonas, [Eubacterium]_xylanophilum_group, [Eubacterium]_brachy_group and [Bacteroides]_pectinophilus_group were the characteristic genera of male VPA rats. Between the female VPA and female control groups, 124 annotated differentially abundant fecal metabolites were identified without differentially enriched KEGG pathways. Ruminiclostridium, Acetatifactor, Desulfovibrio, [Eubacterium]_xylanophilum_group and Candidatus_Saccharimonas were the characteristic genera of female VPA rats. Correlation analysis revealed a tight relationship between the GM and fecal metabolites in VPA rats of both sexes. In conclusion, alterations in the GM and fecal metabolites in VPA rats showed sex-specific differences. The therapy for ASD might be different between sexes in the future.

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

MusT-In Therapy (Effect of Music Therapy and Interaction with Typically Developing Peers) for improving social interaction in children with severe autism spectrum disorder - Study protocol.

Background: Autism Spectrum Disorder (ASD) affects 1 out of every 54 children in the United States, impairing their social skills and independence. Current evidence from clinical trials and meta-analyses suggests that, individually, both music therapy and interaction with typically developing peers (TD) can improve social skills in children with ASD. However, there are no clearly defined parameters for the combined efficacy of these interventions and their long-term effects. Therefore, conducting new studies in this area is of utmost importance not only for the scientific community but also for children with ASD and their caregivers. Objective: To evaluate the effect of a new add-on therapy on improving social interaction skills in children with severe ASD –the MusT-In Therapy– which combines music therapy and interaction with TD peers. Methods: This is a phase II single-center, two-arm, parallel-group, randomized 1:1, assessor-blinded trial. 116 children with severe ASD (3-6 years old) will be assigned to either the standard of care or 30 weekly sessions of the MusT-In therapy plus standard of care. Improvement in social interaction will be assessed after 30 therapy sessions with the Vineland Scale 3rd edition as the primary outcome. Follow-up assessment of the outcome will be at 1 and 3 months after the intervention has finished. Discussion: Given the lack of robust evidence-based therapies for ASD, the development of new treatments is paramount. Children with severe ASD have been underrepresented in previous trials and parental burden increases with the severity of the spectrum. If our intervention proves to be effective it could be the basis of a new treatment option.

Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder-A Systematic Review.

Autism spectrum disorder (ASD) and cerebral palsy (CP) are some of the most common neurodevelopmental diseases. They have multifactorial origin, which means that each case may manifest differently from the others. In patients with ASD, symptoms associated with deficits in social communication and characteristic, repetitive types of behaviors or interests are predominant, while in patients with CP, motor disability is diagnosed with accompanying cognitive impairment of various degrees. In order to minimize their adverse effects, it is necessary to promptly diagnose and incorporate appropriate management, which can significantly improve patient quality of life. One of the therapeutic possibilities is stem cell therapy, already known from other branches of medicine, with high hopes for safe and effective treatment of these diseases. Undoubtedly, in the future we will have to face the challenges that will arise due to the still existing gaps in knowledge and the heterogeneity of this group of patients. The purpose of this systematic review is to summarize briefly the latest achievements and advances in stem cell therapy for ASD and CP.

Effect of hyperbaric oxygen therapy and Tomatis sound therapy in children with autism spectrum disorder

Many therapeutic and dietary regimens have been studied for children with autism spectrum disorder (ASD) in the last three decades. We aimed to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) and Tomatis sound therapy (TST) in an Egyptian cohort of children with ASD. This study was a prospective, open label, randomized interventional clinical trial. One hundred forty-six children with ASD with no previous rehabilitation therapy were enrolled in our study. Patients were randomly divided into four groups: the first group received hyperbaric oxygen therapy, the second group received Tomatis sound therapy, the third group received a combination of both modalities, and the fourth group, the control group, received no intervention. We found that the combination of Tomatis sound therapy with hyperbaric oxygen therapy had a superior effect in improving autism symptoms than each intervention alone (CARS after therapy 35.04 ± 13.38 versus 49.34 ± 17.54 before the intervention, p < 0.001). The combination of both modalities may be helpful for children with ASD. The most distinctive evidence that supports the use of combination therapy for ASD is still controversial; however, our study provides some evidence of the benefit of combination therapy for children with ASD. Future studies should use a more sophisticated research design and begin by finding a consistent baseline measure that can be used to evaluate the effects of these therapies for ASD.

Effectiveness of music therapy for autism spectrum disorder, dementia, depression, insomnia and schizophrenia: update of systematic reviews.

BackgroundMusic therapy (MT) aims at maintaining, restoring and furthering physical/emotional/mental health. This review assesses effectiveness of MT and its methods for autism spectrum disorder (ASD), dementia, depression, insomnia and schizophrenia.MethodsA search for systematic reviews and health technology assessment reports was conducted and yielded 139 hits. Given the large amount, we focused on five frequent diagnostic groups with available Cochrane reviews. A second search was conducted in four databases. Two authors independently performed study selection, data extraction and assessed methodological quality. Only trials with moderate/low risk of bias (RoB) were selected.ResultsTen randomized controlled trials (1.248 participants) met inclusion criteria. For schizophrenia, no studies with low/moderate RoB were found; therefore, updating was not possible. The Cochrane authors stated that quality of life (QoL), social functioning, global/mental state improved for schizophrenia, but not global functioning. For ASD, MT improved behaviour, social communication, brain connectivity and parent–child relationship. For depression, mood was enhanced, and for insomnia, sleep quality, stress, anxiety, total sleep time, disease severity and psychological QoL improved. MT positively affected mood, neuropsychiatric behaviour, apathy, communication and physical functions for dementia; behavioural/psychological symptoms improved only in severe, and memory and verbal fluency only in mild Alzheimer’s disease. Cognition improved for dementia in one of four studies. Both active (playing music) and receptive (listening to music) methods were used for dementia, whereas for ASD and depression, active methods were applied. For insomnia, only receptive methods were used.ConclusionThese findings provide evidence that MT helps patients improving their physical/psychosocial health. More research investigating long-term effects is needed.

FMR1 and Autism, an Intriguing Connection Revisited.

Autism Spectrum Disorder (ASD) represents a distinct phenotype of behavioral dysfunction that includes deficiencies in communication and stereotypic behaviors. ASD affects about 2% of the US population. It is a highly heritable spectrum of conditions with substantial genetic heterogeneity. To date, mutations in over 100 genes have been reported in association with ASD phenotypes. Fragile X syndrome (FXS) is the most common single-gene disorder associated with ASD. The gene associated with FXS, FMR1 is located on chromosome X. Accordingly, the condition has more severe manifestations in males. FXS results from the loss of function of FMR1 due to the expansion of an unstable CGG repeat located in the 5′′ untranslated region of the gene. About 50% of the FXS males and 20% of the FXS females meet the Diagnostic Statistical Manual 5 (DSM-5) criteria for ASD. Among the individuals with ASD, about 3% test positive for FXS. FMRP, the protein product of FMR1, is a major gene regulator in the central nervous system. Multiple pathways regulated by FMRP are found to be dysfunctional in ASD patients who do not have FXS. Thus, FXS presents the opportunity to study cellular phenomena that may have wider applications in the management of ASD and to develop new strategies for ASD therapy.