Autism Spectrum Disorder Symptoms Research Articles

Therapeutic potential of CBD in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior. Despite extensive research, effective pharmacological interventions for ASD remain limited. Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has potential therapeutic effects on several neurological and psychiatric disorders. CBD interacts with the endocannabinoid system, a complex cell-signaling system that plays a crucial role in regulating various physiological processes, maintaining homeostasis, participating in social and behavioral processing, and neuronal development and maturation with great relevance to ASD. Furthermore, preliminary findings from clinical trials indicate that CBD may have a modulatory effect on specific ASD symptoms and comorbidities in humans. Interestingly, emerging evidence suggests that CBD may influence the gut microbiota, with implications for the bidirectional communication between the gut and the central nervous system. CBD is a safe drug with low induction of side effects. As it has a multi-target pharmacological profile, it becomes a candidate compound for treating the central symptoms and comorbidities of ASD.

Automated Detection of Autism Spectrum Disorder Symptoms using Text Mining and Machine Learning for Early Diagnosis

Automated Detection of Autism Spectrum Disorder Symptoms using Text Mining and Machine Learning for Early Diagnosis

The Combination of Mind and Brain Alteration in A Resource-Limited Country: Autism Spectrum Disorders and Epilepsy in A Child Psychiatry Unit in Dakar

Purpose of the study: Autism spectrum disorders (ASD) and epilepsy can coexist in the same person, constituting poor bilateral prognosis factors. This study describes the sociodemographic elements of patients with ASD and studies the clinico-paraclinical aspects of their epilepsy and its evolution in 2003. Patients and Methods: Cross-sectional and descriptive study in Child psychiatry at CHNU Fann, with analysis of the files of all patients followed between January 2004 and September 2018 for ASD with/without epilepsy. We used a standardized survey with several items. Results: Forty -five patients with ASD collected, with an epileptic frequency of 37.8%. The main history was fetal suffering (24.4%) and parental inbreeding (22.2%). Most of the symptoms of ASD were seen before 3 years old (66.6%) and epilepsy started before 5 years (94%). Seizures were generalized (58.8%), mainly tonic-clonic (80%) or focal (35.3%), with a frequency of 2 seizures / day at 1 seizure / week. The EEG showed abnormalities in frontal areas in 60%, and Centro-parietal in 26.6%. Brain imaging and evoked auditory potential were normal respectively in 93.9%, and 87.2%. Management was multimodal for ASD (neuropsychological, psychomotor, speech therapy) and medicated for epilepsy, mainly by monotherapy (82.4%) with Valproate (58.8%), Phenobarbital (17.6). Forty percent of patients were out of school and 55.6% in primary school. Twenty-five patients were self-reliant to moderately independent, mainly the epileptics (60%). The 2023 evaluation of this cohort concerns 60% of patients with epilepsy in complete remission and behavioral and language stability under continuous management. Conclusion: We find a statistic difference by age between epilepsy and ASD with a genetic predisposition related to parental inbreeding and a family history of ASD and epilepsy and to a lesser extent the existence of acute fetal suffering. The contribution of EEG was significant with a predilection of frontal abnormalities whose epileptic treatment appears to improve the impact in children's behavioral disorders.

Short Report: Measuring the Behavioral Disturbance of Autism Spectrum Disorder by Cohen-Mansfield Agitation Inventory

Introduction: Cohen-Mansfield Agitation Inventory (CMAI) has originally been developed for the evaluation of agitation in Alzheimer’s disease. Reliable tools for measuring behavioral symptoms in autism spectrum disorder (ASD) are missing. Methods: The reproducibility of the CMAI was evaluated in 26 patients. The CMAI-questionnaire was filled for each participant by three different nurses. The measurement was repeated by the primary caregiver for 15 patients. Agreement between nurses was measured using Cohen’s weighed kappa, intraclass correlation coefficient (ICC) was used to evaluate intra-rater reliability and Cronbach’s alphas to quantify internal consistency. Results: The inter-rater reliability was found to be substantial for all items ICC 0.64 (95%CI 0.43-0.80). Cronbach’s alpha was good for the whole CMAI score (α=0.87 with 95% CI 0.82-0.91). No statistically significant differences were seen in the CMAI-scores between repeated measurements. Conclusions: The CMAI may be a reasonably reliable tool to follow-up changes in behavioral symptoms of ASD.

Children autism spectrum disorder and gut microbiota: A bibliometric and visual analysis from 2000 to 2023

Autism spectrum disorder (ASD) has evolved from a narrow and rare childhood-onset disorder to a widely publicized and researched lifelong disease recognized as common and significantly heterogeneous. Researchers have suggested that gastrointestinal symptoms in ASD may be a manifestation of an underlying inflammatory process. However, there is a lack of bibliometric analysis of ASD and gut microbiota in children. Accordingly, this study conducts a bibliometric analysis of ASD and gut microbiota in children from 2000 to 2023, explores the current status and cutting-edge trends in the field of ASD and gut microbiota in children, and identifies new directions for future research. The literature on ASD and gut microbiota in children was screened using the Web of Science Core Collection from 2000 to 2023. Annual publications, countries, institutions, authors, journals, keywords, and references were visualized and analyzed using CiteSpace 5.8. R3 and VOSviewer1.6.18. This study included 1071 publications. Since the beginning of 2011, the overall number of articles shows an upward trend. The most productive country and institution are the United States and the University of California system, respectively. The most frequently cited author is Kang Dae-Wook, with 790 citations, who has contributed significantly to this field. Timothy Dinan is the most prolific author, with 34 articles. The journal with the most published articles on this topic is Nutrients, whereas PLOS One is the most cited journal. The most used keyword is “gut microbiota,” and the reference for the highest outbreak intensity is Hsiao. The research hotspots and trends predicted in this study provide a reference for further in-depth research in this field.

Прогнозування ризику розвитку розладів аутистичного спектра в дітей з епілептичними енцефалопатіями

Predicting the risk of developing autism spectrum disorders (ASD) in children with epileptic encephalopathies (EE) is an important task, which makes it possible to identify the most significant risk factors and develop ways of their modification. Purpose - to develop a model for predicting the risk of developing ASD in young children with EE. Materials and methods. 75 children aged 0-3 years with the onset of epileptic seizures in the first year of life, clinical manifestations of EE were examined. The most informative clinical, neurophysiological, and neuroimaging indicators for predicting the risk of clinical manifestations of ASD were determined: age of onset of epileptic seizures, index of spike-wave activity during NREM sleep, frequency and amplitude of alpha rhythm, frequency and amplitude of epileptiform activity, fractional anisotropy and mean diffusion coefficient in the Broca’s center, fractional anisotropy in the Wernicke center and knee of the corpus callosum. The multiple linear regression method was used to predict the risk of developing ASD symptoms. Results. A model for predicting the risk of developing clinical manifestations of ASD in children with EE has been developed. It was established that the risk of developing clinical manifestations of ASD increases with a decrease in the age of onset of epileptic seizures, decrease in the frequency and amplitude of the alpha rhythm according to electroencephalography (EEG) data, increase of the index of spike-wave activity, frequency and amplitude of epileptiform activity, increase in the index of fractional anisotropy in the anterior part of the arcuate tract, decrease in the average diffusion coefficient in the area of the Broca’s center, fractional anisotropy in the Wernicke center and the knee of the corpus callosum according to magnetic resonance tractography. Conclusions. A regression model for predicting the risk of clinical manifestations of ASD in children with EE was developed with an average error of approximation of 13.2% and a coefficient of determination of 0.74, which is recommended for use in clinical practice in order to form groups of children at high risk of ASD. Such children require further dynamic monitoring and early intervention by specialists of a multidisciplinary team for timely identification and correction of ASD symptoms The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Knowledge of Childhood Autism among Health Workers of Peshawar: A Cross-Sectional Study

Background: Early detection of Autism Spectrum Disorder (ASD) symptoms is crucial for timely intervention services and a better prognosis. Healthcare professionals play a pivotal role in recognizing ASD features, diagnosis, and providing support. This study aimed to assess the knowledge of healthcare workers in Peshawar regarding childhood autism. Objective: The objective of this study was to evaluate the level of knowledge among healthcare professionals in Peshawar, Pakistan, regarding the early symptoms, diagnosis, and intervention strategies for Autism Spectrum Disorder (ASD), in order to identify knowledge gaps and inform the development of targeted educational and training programs. Methods: This cross-sectional study was conducted from September 2021 to February 2022 in public and private hospitals in Peshawar, Pakistan. Data were collected using the convenience sampling method. A total of 270 healthcare professionals (Doctors, Dentists, Psychologists, Occupational Therapists, Physical Therapists, and Speech & Language Pathologists) participated. Data analysis was performed using SPSS version 22. Descriptive analysis calculated the mean of each domain and the total score, and frequencies for gender, age, and occupation. Results: The total mean score of the study population was 10.40. The mean score in Domain 1 (Social Interaction) was 4.73 (SD ±1.53), in Domain 2 (Language) was 0.60 (SD ±0.499), in Domain 3 (Behaviors) was 2.38 (SD ±1.102), and in Domain 4 (Etiology) it was 2.74 (SD ±1.214). Conclusion: Healthcare professionals in Peshawar, Pakistan, demonstrated limited knowledge about the early symptoms of Autism Spectrum Disorder. These findings have significant implications for policy and practice, health profession program directors, and future research.

Short report: Autistic symptoms in Sotos syndrome, preliminary results from a case-control study

BackgroundAn extremely heterogeneous neuropsychological phenotype has been reported in Sotos Syndrome (SoS), including socio-communicative and behavioral difficulties referred to Autism Spectrum Disorder (ASD). Nonetheless, to date, only few data are available on the topic. AimTo investigate ASD symptoms within a sample of children with SoS in comparison to a matched control group of individuals with idiopathic ASD. MethodsA convenience sample of SoS (n = 33, age: 9.8 ± 4.1) and ASD (n = 33, age: 9.9 ± 4.1), was included. Autistic symptoms’ assessment was performed through the administration of the Autism Diagnostic Observation Schedule–Second Edition- ADOS-2, the Social Responsiveness Scale -SRS and the Social Communication Questionnaire-SCQ. Results72.7% of SoS children presented mild to moderate levels of ASD symptoms as measured by the ADOS-2. Oneway ANOVA analysis showed that SoS individuals presenting lower IQ demonstrated higher ASD symptom’s level (p = 0.01). No statistically significant differences emerged between the SoS and ASD groups within the SRS total score domain (p = 0.95). Conclusions and implicationsOur results support the evidence for an increased risk for ASD in SoS, suggesting that the ASD symptoms’ assessment should be regularly performed in SoS children, with subsequent important implications in terms of therapeutic strategies and later outcome.

Serum Zonulin, Claudin-5, junction Adhesion Molecule-A, Occludin and Tricellulin levels in children with autism spectrum disorder

Introduction The aim of this study is to determine whether there is a difference in serum Zonulin, Occludin, Claudin-5, Junctional Adhesion Molecule-A (JAM-A), Tricellulin levels between individuals diagnosed with Autism Spectrum Disorder (ASD) and healthy controls. Method A total of 40 children with ASD and 40 controls aged 2-12 years were enrolled in this study. Serum levels of biochemical variables were determined using commercial enzyme-linked immunosorbent assay kits. Childhood Autism Rating Scale, Autism Behavior Checklist and Aberrant Behavior Checklist were applied to determine the severity of autistic symptoms. Results Serum Zonulin, Occludin, Claudin-5, Tricellulin and JAM-A levels did not differ between the study and control groups. There was no relationship between the severity of ASD symptoms and biochemical parameters. Discussion Although the findings of the study suggest that the permeability of the Blood Brain Barrier (BBB) is not effective in the etiology of ASD, there is a need for new studies addressing the limitations of our study in a larger and heterogeneous sample in order to generalize the findings.

Nutritional medical therapy in autism spectrum disorder

Objectives. This study aimed to assess the effectiveness of commonly used nutritional medical therapies in children with autism spectrum disorder (ASD). Method. The study explores the intricate relationship between ASD and nutritional medical therapy. Individuals with ASD often exhibit compromised gastrointestinal (GI) health, including issues with intestinal motility, adverse reactions to certain foods, and nutrient absorption deficiencies. These problems may be caused or exacerbated by restrictive eating behaviors, food preferences, and nutritional deficiencies. Those with GI conditions often display heightened behavioral deficits and imbalances in the overall composition of the intestinal microbiome. Results. The research underscores the importance of an individually tailored approach, considering the diverse nutritional needs and unique preferences of individuals with ASD. Analysis of current studies highlights the potential impact of personalized diets on the quality of life within the complex context of GI conditions associated with ASD. The benefits of current nutritional therapies are summarized, and the mixed results in addressing ASD are analyzed. Gluten-free and casein-free diets, the ketogenic diet, supplementation with fatty acids, and the use of pre-/probiotics demonstrate improvements in managing GI and behavioral symptoms associated with ASD. Customizing the diet is recommended as a multidisciplinary approach, given the complexity of GI-related conditions within the ASD diagnosis and their association with behavioral and neurological deficits. The significance of the results lies in supporting a personalized approach in managing specific ASD symptoms, with a focus on individual nutritional needs. Conclusions. Managing ASD symptoms requires a personalized approach, considering individual nutritional needs, food preferences, and different clinical manifestations.

Intermittent Hypobaric Hypoxia Ameliorates Autistic-Like Phenotypes in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body. Here, using two mouse models of ASD, male Shank3B -/- and Fmr1 -/y mice, we found that IHH training at an altitude of 5,000 m for 4 h per day, for 14 consecutive days, ameliorated autistic-like behaviors. Moreover, IHH training enhanced hypoxia inducible factor (HIF) 1α in the dorsal raphe nucleus (DRN) and activated the DRN serotonergic neurons. Infusion of cobalt chloride into the DRN, to mimic IHH in increasing HIF1α expression or genetically knockdown PHD2 to upregulate HIF1α expression in the DRN serotonergic neurons, alleviated autistic-like behaviors in Shank3B -/- mice. In contrast, downregulation of HIF1α in DRN serotonergic neurons induced compulsive behaviors. Furthermore, upregulating HIF1α in DRN serotonergic neurons increased the firing rates of these neurons, whereas downregulation of HIF1α in DRN serotonergic neurons decreased their firing rates. These findings suggest that IHH activated DRN serotonergic neurons via upregulation of HIF1α, and thus ameliorated autistic-like phenotypes, providing a novel therapeutic option for ASD.

The impact of primary care access on autism spectrum disorder awareness in an underserved population.

American Academy of Pediatrics (AAP) recommendations for Autism Spectrum Disorder (ASD) screening do not specifically address safety-net clinics, which provide multidisciplinary healthcare services to underserved patients. This project explored the potential for ASD screening in safety-net clinics by assessing parental perceived knowledge of ASD at JayDoc Free Clinic, a student-run safety-net clinic in Wyandotte County, Kansas. May through December 2022, patients who reported to be the parent of a minor received a demographic survey and a Likert-style questionnaire assessing perceived knowledge of ASD, including understanding the importance of ASD screening and ASD signs and symptoms. Responses were categorized into positive, negative, and unsure. Demographic variables included the minor's primary care provider (PCP) status. Results were analyzed using bivariate analysis, with chi-square tests for significance (p-value ≤ 0.05). Of the 52 participants who completed at least one Likert response, 55.8% reported their child had a PCP. Responses were somewhat balanced with 44.2% positive for understanding the importance of ASD screening and 53.8% positive for understanding ASD signs and symptoms. For understanding the signs and symptoms of ASD, an unsure response (32.7% of responses) was statistically associated with a lack of PCP (p = 0.017). The balance of positive with negative and unsure responses could reflect lack of ASD knowledge and may relate to healthcare inaccessibility. This is consistent with the significant association between lack of PCP and unsure responses for understanding ASD signs and symptoms. ASD screening and education in safety-net clinics like JayDoc could be valuable, particularly for children without a PCP.

Gut microbiota functional profiling in autism spectrum disorders: bacterial VOCs and related metabolic pathways acting as disease biomarkers and predictors.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder. Major interplays between the gastrointestinal (GI) tract and the central nervous system (CNS) seem to be driven by gut microbiota (GM). Herein, we provide a GM functional characterization, based on GM metabolomics, mapping of bacterial biochemical pathways, and anamnestic, clinical, and nutritional patient metadata. Fecal samples collected from children with ASD and neurotypical children were analyzed by gas-chromatography mass spectrometry coupled with solid phase microextraction (GC-MS/SPME) to determine volatile organic compounds (VOCs) associated with the metataxonomic approach by 16S rRNA gene sequencing. Multivariate and univariate statistical analyses assessed differential VOC profiles and relationships with ASD anamnestic and clinical features for biomarker discovery. Multiple web-based and machine learning (ML) models identified metabolic predictors of disease and network analyses correlated GM ecological and metabolic patterns. The GM core volatilome for all ASD patients was characterized by a high concentration of 1-pentanol, 1-butanol, phenyl ethyl alcohol; benzeneacetaldehyde, octadecanal, tetradecanal; methyl isobutyl ketone, 2-hexanone, acetone; acetic, propanoic, 3-methyl-butanoic and 2-methyl-propanoic acids; indole and skatole; and o-cymene. Patients were stratified based on age, GI symptoms, and ASD severity symptoms. Disease risk prediction allowed us to associate butanoic acid with subjects older than 5 years, indole with the absence of GI symptoms and low disease severity, propanoic acid with the ASD risk group, and p-cymene with ASD symptoms, all based on the predictive CBCL-EXT scale. The HistGradientBoostingClassifier model classified ASD patients vs. CTRLs by an accuracy of 89%, based on methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, ethanol, butanoic acid, octadecane, acetic acid, skatole, and tetradecanal features. LogisticRegression models corroborated methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, skatole, and acetic acid as ASD predictors. Our results will aid the development of advanced clinical decision support systems (CDSSs), assisted by ML models, for advanced ASD-personalized medicine, based on omics data integrated into electronic health/medical records. Furthermore, new ASD screening strategies based on GM-related predictors could be used to improve ASD risk assessment by uncovering novel ASD onset and risk predictors.

Perspectives on Autism Spectrum Disorder Diagnosis, Symptoms, Treatment and Gender Roles: A Qualitative Study of Similarities and Differences between Sexes.

This study aims to compare the experiences of women and men of different age groups with regard to their first autism spectrum disorder (ASD) diagnosis, symptoms, treatment, and gender roles to inform our understanding in clinical practice of differences as well as similarities. Semi-structured interviews were conducted amongst 22 women (n = 12) and men (n = 10) in three adult age groups regarding their diagnostic process, symptoms, treatment, and gender roles. Participants also filled out questionnaires on gender traits, social support, coping, and quality of life. Framework analysis guidelines were followed to identify subthemes within the three pre-defined key themes of the semi-structured interviews, and quantitative analyses were performed on the questionnaire results. Women often had caregiver roles and were more focused on social and family-oriented life aspects than men. Family and societal expectations may have been different for women from an early age onward and were considered burdensome by some, but not all. Views on ASD diagnosis, symptoms, and treatment were largely individually determined. The questionnaire results mostly showed no significant sex differences. Perceived gender roles differed between participants. In diagnosis and treatment, awareness of general gender differences and gender roles is important, but inter-individual differences and similar experiences in men should not be overlooked.

Intranasal oxytocin in a genetic animal model of autism

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly characterized by deficient sociability and repetitive behaviors. Effective treatment for the core symptoms of ASD is still lacking. Behavioral interventions show limited effectiveness, while pharmacotherapy focuses on the amelioration of secondary symptomatology. Oxytocin (OXT) is a neuropeptide known for its prosocial impact, making it a candidate drug for ASD treatment. Its alleviating effect has been and still is widely researched, but outcomes reported by clinical studies are ambiguous. We examined the effect of daily intranasal OXT (0.8 IU/kg) administration for 4 weeks on the ASD-like phenotype in Shank3−/− adult mice. Animals treated with OXT spent twice as much time interacting with the social partner as early as after 2 weeks of treatment. Furthermore, OXT-treated mice exhibited reduced explorative behavior by 50%, after 4 weeks of treatment, and a 30% reduction in repetitive behavior, 4 weeks after treatment termination. One-fold higher sociability and 30% reduced exploration due to OXT lasted up to 4 weeks following the treatment termination. However, social disinterest was elevated by roughly 10% as well, indicating a form of social ambivalence. Obtained results support the therapeutic potential of intranasally administered OXT in alleviating social shortfalls in a genetic model of ASD. Subsequent research is necessary to elucidate the benefits and risks of the long-term OXT administration, as well as its applicability in other ASD models and the potential treatment effect on social communication, which was not measured in the present study.

Risk factors and clinical correlates of sensory dysfunction in preschool children with and without autism spectrum disorder.

Sensory dysfunction is a common feature of autism spectrum disorder (ASD). The objectives of this analysis were to examine risk factors and clinical correlates of sensory dysfunction in preschool children with and without ASD. Children aged 2-5 years were enrolled in a multi-site case-control study. Data were collected in eight areas across the United States in three phases. Caregivers completed an interview with questions on assisted delivery, maternal alcohol use, maternal anxiety during pregnancy, pregnancy weight gain, neonatal jaundice, preterm birth, and child sensory diagnosis given by a healthcare provider. Caregivers also completed an interview and questionnaires on sensory symptoms and clinical correlates of sensory dysfunction in their child. There were 2059 children classified as ASD, 3139 as other developmental delay or disability (DD), and 3249 as population comparison (POP). Caregivers reported significantly more sensory diagnoses and sensory symptoms in children classified as ASD than DD or POP (23.7%, 8.6%, and 0.8%, respectively, for a sensory diagnosis and up to 78.7% [ASD] vs. 49.6% [DD] for sensory symptoms). Maternal anxiety during pregnancy and neonatal jaundice were significantly associated with a sensory diagnosis and certain sensory symptoms in children with ASD and DD. Children's anxiety, attention deficits/hyperactivity, and sleep problems were significantly albeit subtly correlated with both a sensory diagnosis and sensory symptoms in children with ASD and DD. These findings support sensory dysfunction as a distinguishing symptom of ASD in preschool children and identify risk factors and clinical correlates to inform screening and treatment efforts in those with atypical development.

Speech Development of Children with ASD: A Neuropsychological Approach

Effective identification, support, and development of children’s abilities is a priority task of the education system in Russia. This demands deeper research based on the use of modern diagnostic technologies and neuropsychological tools, especially in what concerns children with impaired development, such as autism spectrum disorders (ASD). Neuropsychological rehabilitation of children with ASD remains a poorly understood yet critical problem. Here, we explore common neuropsychological tools employed in Russia for diagnostics and therapy of ASD in childhood. The prospects of these methods to study the speech characteristics of such children were substantiated. The study is based on a survey of 20 parents of 20 children aged 4–6 years who attend the “WE ARE TOGETHER” Special Kindergarten for Children with Autism Spectrum Disorders at Kazan Federal University (Russia). The speech characteristics of the children, starting from an early age, were thoroughly investigated during the experiment with the help of neuropsychological tools. The latter included game tasks to test social, cognitive, motor, neurodynamic, and regulatory skills, as well as the analysis of the transcripts of the interviews with both children and their parents. The results obtained facilitate the introduction of the neuropsychological approach to diagnose speech disorders in preschool children with ASD, and it can be further improved by experts in the rehabilitation and education of children exhibiting ASD symptoms.

AST-001 Improves Social Deficits and Restores Dopamine Neuron Activity in a Mouse Model of Autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social communication and social interaction, restricted and repetitive behavior, and interests. The core symptoms of ASD are associated with deficits in mesocorticolimbic dopamine pathways that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). AST-001 is an investigational product currently in a phase 3 clinical trial for treating the core symptoms of ASD, with L-serine as the API (active pharmaceutical ingredient). Because the causes of ASD are extremely heterogeneous, a single genetic ASD model cannot represent all autism models. In this paper, we used the VPA-exposed model, which is more general and widely used than a single genetic model, but this is also one of the animal models of autism. Herein, we conducted experiments to demonstrate the efficacy of AST-001 as L-Serine that alters the regulation of the firing rate in dopamine neurons by inhibiting small conductance Ca2+-activated K+ channels (SK channels). Through these actions, AST-001 improved sociability and social novelty by rescuing the intrinsic excitabilities of dopamine neurons in VPA-exposed ASD mouse models that showed ASD-related behavioral abnormalities. It is thought that this effect of improving social deficits in VPA-exposed ASD mouse models is due to AST-001 normalizing aberrant SK channel activities that slowed VTA dopamine neuron firing. Overall, these findings suggest that AST-001 may be a potential therapeutic agent for ASD patients, and that its mechanism of action may involve the regulation of dopamine neuron activity and the improvement of social interaction.

Screen Time and Autism Spectrum Disorder

Contemporary studies raise concerns regarding the implications of excessive screen time on the development of autism spectrum disorder (ASD). However, the existing literature consists of mixed and unquantified findings. To conduct a systematic review and meta-analyis of the association between screen time and ASD. A search was conducted in the PubMed, PsycNET, and ProQuest Dissertation & Theses Global databases for studies published up to May 1, 2023. The search was conducted independently by 2 authors. Included studies comprised empirical, peer-reviewed articles or dissertations published in English with statistics from which relevant effect sizes could be calculated. Discrepancies were resolved by consensus. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Two authors independently coded all titles and abstracts, reviewed full-text articles against the inclusion and exclusion criteria, and resolved all discrepancies by consensus. Effect sizes were transformed into log odds ratios (ORs) and analyzed using a random-effects meta-analysis and mixed-effects meta-regression. Study quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Publication bias was tested via the Egger z test for funnel plot asymmetry. Data analysis was performed in June 2023. The 2 main variables of interest in this study were screen time and ASD. Screen time was defined as hours of screen use per day or per week, and ASD was defined as an ASD clinical diagnosis (yes or no) or ASD symptoms. The meta-regression considered screen type (ie, general use of screens, television, video games, computers, smartphones, and social media), age group (children vs adults or heterogenous age groups), and type of ASD measure (clinical diagnosis vs ASD symptoms). Of the 4682 records identified, 46 studies with a total of 562 131 participants met the inclusion criteria. The studies were observational (5 were longitudinal and 41 were cross-sectional) and included 66 relevant effect sizes. The meta-analysis resulted in a positive summary effect size (log OR, 0.54 [95% CI, 0.34 to 0.74]). A trim-and-fill correction for a significant publication bias (Egger z = 2.15; P = .03) resulted in a substantially decreased and nonsignificant effect size (log OR, 0.22 [95% CI, -0.004 to 0.44]). The meta-regression results suggested that the positive summary effect size was only significant in studies targeting general screen use (β [SE] = 0.73 [0.34]; t58 = 2.10; P = .03). This effect size was most dominant in studies of children (log OR, 0.98 [95% CI, 0.66 to 1.29]). Interestingly, a negative summary effect size was observed in studies investigating associations between social media and ASD (log OR, -1.24 [95% CI, -1.51 to -0.96]). The findings of this systematic review and meta-analysis suggest that the proclaimed association between screen use and ASD is not sufficiently supported in the existing literature. Although excessive screen use may pose developmental risks, the mixed findings, the small effect sizes (especially when considering the observed publication bias), and the correlational nature of the available research require further scientific investigation. These findings also do not rule out the complementary hypothesis that children with ASD may prioritize screen activities to avoid social challenges.

Disentangling sensory precision and prior expectation of change in autism during tactile discrimination

Predictive coding theories suggest that core symptoms in autism spectrum disorders (ASD) may stem from atypical mechanisms of perceptual inference (i.e., inferring the hidden causes of sensations). Specifically, there would be an imbalance in the precision or weight ascribed to sensory inputs relative to prior expectations. Using three tactile behavioral tasks and computational modeling, we specifically targeted the implicit dynamics of sensory adaptation and perceptual learning in ASD. Participants were neurotypical and autistic adults without intellectual disability. In Experiment I, tactile detection thresholds and adaptation effects were measured to assess sensory precision. Experiments II and III relied on two-alternative forced choice tasks designed to elicit a time-order effect, where prior knowledge biases perceptual decisions. Our results suggest a subtler explanation than a simple imbalance in the prior/sensory weights, having to do with the dynamic nature of perception, that is the adjustment of precision weights to context. Compared to neurotypicals, autistic adults showed no difference in average performance and sensory sensitivity. Both groups managed to implicitly learn and adjust a prior that biased their perception. However, depending on the context, autistic participants showed no, normal or slower adaptation, a phenomenon that computational modeling of trial-to-trial responses helped us to associate with a higher expectation for sameness in ASD, and to dissociate from another observed robust difference in terms of response bias. These results point to atypical perceptual learning rather than altered perceptual inference per se, calling for further empirical and computational studies to refine the current predictive coding theories of ASD.