Core Autism Spectrum Disorder Research Articles

THE ROLE OF THE ENDOCANNABINOID SYSTEM AND CANNABIDIOL (CBD) IN THE TREATMENT OF AUTISM SPECTRUM DISORDER: EFFICACY, SAFETY, AND COMORBIDITIES

Introduction: Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental disorders characterized by persistent deficits in communication and social interaction, along with restrictive and repetitive behaviors. Conventional interventions often face limitations, prompting interest in alternative treatments, particularly those involving the endocannabinoid system (ECS) and cannabidiol (CBD). Objectives: This study aims to evaluate the role of the ECS and the efficacy of CBD as therapeutic interventions for ASD and its comorbidities. Methods: A literature review was conducted, focusing on articles published in Portuguese, Spanish, and English from 2019 to 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were searched using descriptors: “Cannabidiol,” “Autism,” and “Endocannabinoid System”. Boolean terms “AND” and “OR” refined the results. A total of 7 articles from Medline and 3 from LILACS were initially identified. Results: The review identified 10 relevant articles that provided comprehensive insights into the effects of CBD on core ASD symptoms, including social interaction and anxiety. Most studies reported significant improvements in patients, with minimal adverse effects, emphasizing the safety of CBD compared to traditional treatments. Conclusion: The findings suggest that CBD may offer a promising alternative for treating ASD and its comorbidities, with a favorable safety profile. Continued research is essential to establish effective guidelines for clinical application.

Multilingualism impacts children's executive function and core autism symptoms.

Autism spectrum disorder (ASD) is associated with marked heterogeneity in executive function (EF) abilities. EF components including inhibition and shifting are related to ASD core symptoms such as perspective taking, social communication, and repetitive behavior. Recent research suggests that multilingualism may have a beneficial impact on EF abilities, especially in children with ASD. However, there remains a lack of comprehensive understanding regarding the relationships between multilingualism, EF, and core symptoms in children with ASD. Here, we examined these associations in 7-12-year-old children with and without ASD (N = 116; 53 ASD, Mean age = 9.94 years). Results suggest that multilingual children have stronger parent-reported inhibition, shifting, and perspective-taking skills than monolingual children. Furthermore, we found a significant interaction between diagnosis and multilingual status on inhibition, such that the effects of multilingualism were stronger for children with ASD than typically developing (TD) children. Finally, we found indirect effects of multilingualism on perspective taking, social communication, and repetitive behaviors mediated by EF skills. These results demonstrate the supportive influences multilingual experience might have on bolstering EF and reducing ASD-related symptoms.

Autism Spectrum Disorder in Children: Early Signs and Therapeutic Interventions

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in communication, social interaction difficulties, and repetitive behaviors that can hinder a child’s development. The growing prevalence of autism necessitates early detection and effective intervention strategies. This review summarizes the current knowledge of early indicators of ASD, including brain development markers and behavioral signs visible in infants. It investigates diagnostic processes, emphasizing the importance of timely detection at 18 to 24 months using established screening tools. We discuss a variety of therapeutic approaches, including behavioral interventions, educational strategies such as music therapy, and technological advancements such as speech-generating devices. Furthermore, we investigate pharmacological options for treating associated symptoms, emphasizing the lack of targeted medications for core ASD symptoms. Finally, we present evidence highlighting the positive effects of early intervention on developmental outcomes, advocating for individualized treatment plans to enhance the well-being of children with ASD. This comprehensive overview aims to inform ongoing ASD research and clinical practices.

Gray Matter Volume Correlates of Co-Occurring Depression in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) involves neurodevelopmental syndromes with significant deficits in communication, motor behaviors, emotional and social comprehension. Often, individuals with ASD exhibit co-occurring depression characterized by a change in mood and diminished interest in previously enjoyable activities. Due to communicative challenges and a lack of appropriate assessments in this cohort, co-occurring depression can often go undiagnosed during routine clinical examinations and, thus, its management neglected. The literature on co-occurring depression in adults with ASD is limited. Therefore, understanding the neural basis of the co-occurring psychopathology of depression in ASD is crucial for identifying brain-based markers for its timely and effective management.Using structural MRI and phenotypic data from the Autism Brain Imaging Data Exchange (ABIDE II) repository, we examined the pattern of relationship regional grey matter volume (rGMV) has with co-occurring depression and autism severity within regions of a priori interest in adults with ASD (n = 44; age = 17-28 years). Further, we performed an exploratory analysis of the rGMV differences between ASD and matched typically developed (TD, n = 39; age = 18-31 years) samples. The severity of co-occurring depression correlated negatively with the rGMV of the right thalamus. Additionally, a significant interaction was evident between the severity of co-occurring depression and core ASD symptoms towards explaining the rGMV in the left cerebellum crus II. The results further the understanding of the neurobiological underpinnings of co-occurring depression in adults with ASD towards exploring neuroimaging-based biomarkers in the same cohort.

FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study.

Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD. A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits. Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p < 0.0001), CARS scores decreased from 36.22 to 33.33 (p < 0.0001), SRS scores decreased from 151.17 to 137.5 (p = 0.0002), and the ABC scores decreased 76.39 to 53.17 (p < 0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p = 0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32 mg/L (p = 0.022), while other metabolites showed no significant changes. FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.

Efficacy and safety of JNJ-42165279, a fatty acid amide hydrolase inhibitor, in adolescents and adults with autism spectrum disorder: a randomized, phase 2, placebo-controlled study.

JNJ-42165279, a highly selective and orally bioavailable fatty acid amide (FAA) hydrolase inhibitor, was evaluated for efficacy and safety in adolescents and adults with autism spectrum disorder (ASD) in this phase 2, double-blind, placebo-controlled, multicenter study (NCT03664232). Participants aged 13-35 years, with a diagnosis of ASD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; Autism Diagnostic Observation Schedule, 2nd edition) were randomized (1:1) to 12 weeks of treatment with JNJ-42165279 (25 mg, twice-daily) or placebo. Primary endpoints were the change in the Autism Behavior Inventory (ABI) Core Domain (ABI-CD), ABI-Social Communication (ABI-SC), and ABI-Repetitive/Restrictive Behavior (ABI-RB) scores from baseline to day 85. Of the 61 participants (16 female, 45 male) included in the efficacy analyses, 53 (87%) completed the double-blind treatment. At day 85, the JNJ-42165279 group did not show a statistically significant reduction in ASD symptoms versus placebo, as assessed with ABI-CD (p = 0.284), ABI-SC (p = 0.290), and ABI-RB (p = 0.231). However, the following secondary outcomes exhibited small to moderate changes directionally favoring JNJ-42165279: Social Responsiveness Scale 2 (SRS, p = 0.064), Repetitive Behavior Scale-Revised (RBS-R, p = 0.006), Zarit Burden Interview short version (ZBI, p = 0.063), Child Adolescent Symptom Inventory-Anxiety (CASI-Anx, p = 0.048), and Caregiver Global Impression of Severity (p = 0.075). Notably, versus placebo, JNJ-42165279-treated participants showed increased concentrations of FAAs throughout the treatment period, with those achieving elevated concentrations experiencing the greatest reduction in the SRS total score at day 85. JNJ-42165279 demonstrated an acceptable safety profile. Although primary endpoints were not met, JNJ-42165279 may have a therapeutic effect on certain aspects of core ASD symptoms.

Prevalence Trends and Treatment Patterns of Autism Spectrum Disorder Among Children and Adolescents in the United States from 2017 to 2020.

Autism spectrum disorder (ASD) poses a significant challenge due to its diverse impact on individuals, emphasizing the need for personalized treatment plans. The financial burden of ASD-related healthcare is substantial, necessitating a comprehensive understanding of its prevalence and evolving trends. This study aims to analyze the prevalence and trends of ASD, treatment patterns, gender differences, and racial-ethnic disparities in the United States from 2017 to 2020, utilizing nationally representative data from the National Survey of Children's Health (NSCH). The NSCH, a leading annual national survey, provided rich data on child health. A total of 108,142 participants aged 3-17 years were included, with ASD prevalence assessed based on self-reported diagnoses. Between 2017 and 2020, ASD prevalence in children aged 3-17 was 2.94% (95% confidence interval: 2.68-3.18). Significant disparities were observed: older age and male gender correlated with higher prevalence, while family income-to-poverty ratio and insurance coverage influenced prevalence. Racial/ethnic disparities existed, with Hispanics showing the highest prevalence. Treatment trends showed stability overall, but age influenced behavioral and medication interventions. The prevalence remained stable from 2017 to 2020, with variations in age groups and a significant increase among non-Hispanic Whites. This study highlights a higher but stable overall ASD prevalence, with nuanced disparities among different demographic groups. Gender differences persist, emphasizing the need for tailored interventions. Racial-ethnic disparities call for targeted healthcare strategies. The stability in treatment trends underscores the persistent challenge of addressing core ASD symptoms.

Do Occupational Therapy Goals for Children with Autism Spectrum Disorder Reflect Participation? A Mapping to the ICF - CY and ICF Core Sets Study.

Autism Spectrum Disorder (ASD) is on the rise worldwide with an increasing acknowledgement that its continuum of care to enhance participation should be multidisciplinary. The International Classification of Functioning, Disability, and Health (ICF) and its derivatives ICF - Children and Youth (ICF - CY) and ICF Core Sets have been increasingly used among health professionals to enhance communication and documentation of outcomes. This study aimed at investigating the comprehensiveness of the ICF - CY and ICF Core Sets with regard to occupational therapy goals and the extent of participation representation in these goals. Forty occupational therapists working with children with ASD stated their most common three long-term goals. The goals were then mapped to the ICF - CY two level classification. The percentage of goals reflecting "Participation" was calculated. The overlap between ICF - CY and the ICF ASD Core Sets was assessed. A total of 155 goals were extracted, of which only seven (4.5%) related to sensory processing were not linked to the ICF - CY categories. 35.1% of the total linked goals were regarded as reflecting "Participation". 84.5% of ICF - CY categories overlapped with the ICF ASD Core Sets. Categories related to hand function, and taking care of body parts were found to be lacking in the ICF ASD Core Sets. The ICF - CY and the ICF ASD Core Sets may be feasible clinical tools for children with ASD, however, they may not be sufficient to cover occupational therapy goals. Goals also need to be modified to better reflect participation.

Autism spectrum disorder, radicalization, and violence: a forensic perspective

ABSTRACT Some research suggests a higher prevalence of Autism Spectrum Disorder (ASD) among terrorist offenders in comparison to the general population. However, the literature does not achieve consistency in terms of an evidential and theoretical basis that individuals with ASD are especially susceptible to terrorism engagement. Through a case-series analysis, this paper discusses the interplay between ASD and radicalization. We examine how core ASD traits may increase one’s susceptibility to adopting radical ideology, and how internet exposure may contribute to the radicalization process. We comment on how vulnerability may lead to risk, distinguishing between these concepts, and argue that while individuals with ASD may not experience an increased risk of terrorism engagement, traits associated with ASD may increase one’s vulnerability to becoming radicalized when exposed to extremist material online. In considering psychiatric and legal issues, we then make recommendations by examining two notorious Canadian cases. Both individuals were reported to have ASD and received life sentences as a result of committing mass murder, with one individual targeting women, and the other targeting the Muslim population.

Sex differences in the BTBR idiopathic mouse model of autism spectrum disorders: Behavioural and redox-related hippocampal alterations

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental diseases. Epidemiological data report that males have been diagnosed with autism more frequently than females. However, recent studies hypothesize that females’ low incidence might be underestimated due to standard clinical measures of ASD behavioural symptoms, mostly derived from males. Indeed, up to now, ASD mouse models focused mainly on males, considering the prevalence of the diagnosis in that sex. Regarding ASD aetiopathogenesis, it has been recently reported that oxidative stress might be implicated in its onset and development, suggesting an association with ASD typical repetitive behaviours that still need to be disentangled. Here, we investigated possible behavioural and molecular sex-related differences by using the BTBR mouse model of idiopathic ASD. To this aim, animals were exposed to behavioural tests related to different ASD core symptoms and comorbidities, i.e. stereotyped repertoire, social dysfunctions, hyperlocomotion and risk-taking behaviours. Moreover, we analyzed hippocampal levels of pro-oxidant and anti-oxidant enzymes, together with biomarkers of oxidative stress and lipid peroxidation.Our results showed that BTBR females did not display the same patterns for repetitive behaviours as the male counterpart. From a biomolecular point of view, we found an increase in oxidative stress and pro-oxidant enzymes, accompanied by deficient enzymatic anti-oxidant response, only in BTBR males compared to C57BL/6 male mice, while no differences were retrieved in females.Overall, our study suggests that in females there is an urgent need to depict the distinct ASD symptomatology, accompanied by the identification of sex-specific pharmacological targets.

Development of an in vitro compound screening system that replicate the in vivo spine phenotype of idiopathic ASD model mice.

Autism Spectrum Disorder (ASD) is a developmental condition characterized by core symptoms including social difficulties, repetitive behaviors, and sensory abnormalities. Aberrant morphology of dendritic spines within the cortex has been documented in genetic disorders associated with ASD and ASD-like traits. We hypothesized that compounds that ameliorate abnormalities in spine dynamics might have the potential to ameliorate core symptoms of ASD. Because the morphology of the spine is influenced by signal inputs from other neurons and various molecular interactions, conventional single-molecule targeted drug discovery methods may not suffice in identifying compounds capable of ameliorating spine morphology abnormalities. In this study, we focused on spine phenotypes in the cortex using BTBR T + Itpr3 tf /J (BTBR) mice, which have been used as a model for idiopathic ASD in various studies. We established an in vitro compound screening system using primary cultured neurons from BTBR mice to faithfully represent the spine phenotype. The compound library mainly comprised substances with known target molecules and established safety profiles, including those approved or validated through human safety studies. Following screening of this specialized library containing 181 compounds, we identified 15 confirmed hit compounds. The molecular targets of these hit compounds were largely focused on the 5-hydroxytryptamine receptor (5-HTR). Furthermore, both 5-HT1AR agonist and 5-HT3R antagonist were common functional profiles in hit compounds. Vortioxetine, possessing dual attributes as a 5-HT1AR agonist and 5-HT3R antagonist, was administered to BTBR mice once daily for a period of 7days. This intervention not only ameliorated their spine phenotype but also alleviated their social behavior abnormality. These results of vortioxetine supports the usefulness of a spine phenotype-based assay system as a potent drug discovery platform targeting ASD core symptoms.

Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways.

Communication in the form of nonverbal, social vocalization, or crying is evolutionary conserved in mammals and is impaired early in human infants that are later diagnosed with autism spectrum disorder (ASD). Defects in infant vocalization have been proposed as an early sign of ASD that may exacerbate ASD development. However, the neural mechanisms associated with early communicative deficits in ASD are not known. Here, we expressed a constitutively active mutant of Rheb (RhebS16H), which is known to upregulate two ASD core pathways, mTOR complex 1 (mTORC1) and ERK1/2, in Layer (L) 2/3 pyramidal neurons of the neocortex of mice of either sex. We found that cellular mosaic expression of RhebS16H in L2/3 pyramidal neurons altered the production of isolation calls from neonatal mice. This was accompanied by an expected misplacement of neurons and dendrite overgrowth, along with an unexpected increase in spine density and length, which was associated with increased excitatory synaptic activity. This contrasted with the known decrease in spine density in RhebS16H neurons of 1-month-old mice. Reducing the levels of the actin cross-linking and adaptor protein filamin A (FLNA), known to be increased downstream of ERK1/2, attenuated dendrite overgrowth and fully restored spine properties, synaptic connectivity, and the production of pup isolation calls. These findings suggest that upper-layer cortical pyramidal neurons contribute to communicative deficits in a condition known to affect two core ASD pathways and that these mechanisms are regulated by FLNA.

The impact of probiotics on core autism symptoms - A systematic review and meta-analysis of randomized clinical trials

Background & AimsStudies have shown evidence of gut dysbiosis in individuals with autism spectrum disorder (ASD). Various microbiome-modifying treatments, including probiotics, have been proposed. This review systematically assessed the evidence on the effects of probiotics on core autism symptoms in children with ASD. MethodsWe performed a comprehensive literature search in Medline, Embase, CENTRAL, PsycInfo, and clinical trial registries, up to March 2023, and updated on January 10, 2024. Randomized controlled trials (RCTs) of parallel-group and cross-over designs were eligible. The population included individuals below 20 years of age diagnosed with ASD. Trials evaluating the effects of probiotics (any strain or dose) compared to placebo, no treatment, or another intervention were included. The outcomes of interest included the core autism symptoms: deficits in social skills, communication skills, and restricted, repetitive behaviors. No language restrictions were applied. Studies were excluded if an additional active compound was administered. The risk of bias was assessed using the Revised Cochrane Risk of Bias tool (RoB 2). This review was registered in PROSPERO (CRD42023393000). ResultsIn total, 12 RCTs assessing 630 participants were included. A borderline significant beneficial effect of probiotics on core ASD symptoms was found (8 RCTs, mean difference -0.21; 95% CI –0.39 to -0.03). Subgroup analysis according to study type showed a significant positive effect in parallel group trials (6 RCTs, mean difference -0.26; 95% CI –0.48 to -0.05). The pooled effect estimates for the other outcomes didn’t reveal significant differences between the groups. Importantly, the risk of bias was high in nine studies. ConclusionsAvailable data do not provide high-quality evidence supporting the use of probiotics for ASD symptoms in children.

An alpha 5-GABAA receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero.

Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABAA receptors (α5-GABAARs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. SH-053-2'F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate that α5-GABAARs positive allosteric modulators may effectively attenuate some core ASD symptoms.

Harnessing the Gut Microbiome: To What Extent Can Pre-/Probiotics Alleviate Immune Activation in Autism Spectrum Disorder?

Children diagnosed with autism spectrum disorder (ASD) are at an increased risk of experiencing gastrointestinal (GI) discomfort, which has been linked to dysfunctions in the microbiome-gut-brain axis. The bidirectional communication between gut and brain plays a crucial role in the overall health of individuals, and alterations in the gut microbiome can contribute to immune activation and gut-brain dysfunction in ASD. Despite the limited and controversial results of pre-/probiotic applications in ASD, this review comprehensively maps the association between ASD clinical symptoms and specific bacterial taxa and evaluates the efficacy of pre-/probiotics in modulating microbiota composition, reducing inflammatory biomarkers, alleviating difficulties in GI distress, sleep problems, core and other ASD-associated symptoms, as well as relieving parental concerns, separately, in individuals with ASD. Beyond simply targeting core ASD symptoms, this review highlights the potential of pre-/probiotic supplementations as a strategy to modulate gut homeostasis and immune response, and to delineate the potential mechanisms by which its direct or mediating effects can alleviate gut-brain dysfunction and poor nutritional status in ASD management. Further well-designed randomized controlled trials are needed to strengthen the existing evidence and establish optimal protocols for the use of pre-/probiotics in the context of ASD.

NMDA antagonist agents for the treatment of symptoms in autism spectrum disorder: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess the efficacy of NMDA antagonists in ASD (Autism Spectrum Disorder) on the core (communication and social interaction, repetitive behavior) and associated symptoms (irritability) of ASD, as well as their safety. PubMed, CENTRAL, CINHAL, EMBASE, and PsycINFO databases were searched until November 2023. Two authors independently selected the studies and extracted data. Randomized controlled trials assessing the efficacy of NMDA receptor antagonists in participants with ASD aged <18years were included. The quality of the studies was assessed using the Risk of Bias-2 tool. A random-effect meta-analysis model was used to calculate standardized mean differences (SMD) or odds ratios (OR) using meta package in R. This systematic review included ten studies (588 participants). Most studies did not report scales assessing core symptoms of ASD. Meta-analysis of efficacy on ASD core symptoms included three studies (248 participants). NMDA antagonists were not superior to placebo [SMD = 0.29; CI 95% (-1,94; 1.35); I2 = 0%]. NMDA antagonists was not superior to placebo concerning response (four studies, 189 participants) [OR = 2.4; CI 95% (0.69; 8.38); I2 = 35%]. Meta-analysis of efficacy on irritability included three studies (186 participants); NMDA antagonists were not superior to placebo [MD irritability = -1.94; CI 95% (-4.66; 0.77); I2 = 0%]. Compared with placebo, significantly more participants in the NMDA antagonist group reported at least one adverse event (five studies, 310 participants) [OR = 2.04; CI 95% (1.17; 3.57); I2 = 0%]. Current evidence does not support the effectiveness of NMDA antagonists in the treatment of ASD symptoms or irritability. Further research is needed due to the limited and low quality data available. PROSPERO CRD42018110399.

Adverse childhood experiences exacerbate peripheral symptoms of autism spectrum disorder in adults.

Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD). In this study, we evaluate the effects of adverse childhood experiences on multiple ASD phenotypes among both individuals with ASD and those with TD. We combined questionnaire evaluations; Childhood Abuse and Trauma Scale, the Japanese version of the Autism-Spectrum Quotient, Conners' Adult ADHD Rating Scale, the Japanese version of the Impact of Event Scale-Revised, and the Japanese version of the Adolescent/Adult Sensory Profile. Individuals with ASD and those with TD (n = 205 and 104, respectively) were included. There were significant correlations between the extent of adverse childhood experiences and severity of attention-deficit/hyperactivity disorder symptoms, posttraumatic stress disorder symptoms, and hypersensitivity in both participants with ASD and those with TD. By contrast, ASD core symptoms showed no significant correlation with adverse childhood experiences in either group. These results remained consistent after adjusting for age, sex, and the estimated intelligence quotient. These findings suggest the need for a detailed disentanglement of ASD-related core and peripheral symptoms of adverse childhood experiences, which may help to appropriately set outcomes for future early interventions for the childhood experiences of individuals with ASD.

Prenatal broad-spectrum cannabidiol administration prevents an autism-like phenotype in male offspring from a maternal stress/terbutaline rat model

Recently, the diagnosis of autism spectrum disorder (ASD) has increased from 1 in 150 to every 1 in 36 children in the United States, warranting a need for novel prevention and therapeutic strategies. Broad-spectrum cannabidiol oil, free from delta-9-tetrahydrocannabinol, the psychoactive component of cannabis, may be one such therapeutic. It has a high safety profile and is frequently used as a complementary and integrative intervention by persons experiencing symptoms of anxiety, stress, and inflammation. Using a neurodevelopmental rat model of ASD (based on neuroinflammation induced by stress and terbutaline exposure during pre- and postnatal development), we sought to prevent the development of ASD-like behaviors in male offspring by administering broad-spectrum cannabidiol oil to dams throughout pregnancy (10 mg/kg, i.p., daily, embryonic days 3–16). To assess an ASD-like phenotype in the offspring, we used three behavioral measures relevant to three core ASD symptoms: 1) social communication (time spent vocalizing when alone); 2) repetitive behavior (marbles buried during a marble burying test); and 3) social interaction (time spent interacting with a novel conspecific during the three-chamber social interaction test). Broad-spectrum cannabidiol oil given during pregnancy decreased scores for all three ASD-related behavioral responses, resulting in an overall significant prevention of the ASD-like phenotype. These findings highlight the potential of broad-spectrum cannabidiol oil as a complementary and integrative approach for prevention of stressor-induced sequelae relevant to development of an ASD-like phenotype.

Oral edaravone ameliorates behavioral deficits and pathologies in a valproic acid-induced rat model of autism spectrum disorder

Autism spectrum disorder (ASD) is neurodevelopmental disorder with a high incidence rate, characterized by social deficits and repetitive behaviors. There is currently no effective management available to treat the core symptoms of ASD; however, oxidative stress has been implicated in its pathogenesis. Edaravone (EDA), a free-radical scavenger, is used to treat amyotrophic lateral sclerosis (ALS) and acute ischemic stroke (AIS). Here, we hypothesized that an oral formula of EDA may have therapeutic efficacy in the treatment of core ASD symptoms. A rat model of autism was established by prenatal exposure to valproic acid (VPA), and the offsprings were orally treated with EDA at low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg) doses once daily for 28 days starting from postnatal day 25 (PND25). Oral EDA administration alleviated the core symptoms in VPA rats in a dose-dependent manner, including repetitive stereotypical behaviors and impaired social interaction. Furthermore, oral administration of EDA significantly reduced oxidative stress in a dose-dependent manner, as evidenced by a reduction in oxidative stress markers and an increase in antioxidants in the blood and brain. In addition, oral EDA significantly attenuated downstream pathologies, including synaptic and mitochondrial damage in the brain. Proteomic analysis further revealed that EDA corrected the imbalance in brain oxidative reduction and mitochondrial proteins induced by prenatal VPA administration. Overall, these findings demonstrate that oral EDA has therapeutic potential for ASD by targeting the oxidative stress pathway of disease pathogenesis and paves the way towards clinical studies.

Effectiveness of animal-assisted activities and therapies for autism spectrum disorder: a systematic review and meta-analysis.

Given the rising interest in complementary therapeutic strategies for autism spectrum disorder (ASD), this research aims to provide a comprehensive analysis of the impact of animal-assisted activities and therapies (AAAT) on various ASD symptoms. A meticulous search of databases, including Scopus and PubMed, was conducted to gather relevant research on AAAT for ASD. This process led to the selection of 45 studies encompassing 1,212 participants. The chosen studies were then subjected to a meta-analysis to evaluate the efficacy of AAAT in alleviating core ASD symptoms. The meta-analysis revealed significant improvements in several core ASD symptoms due to AAAT. Notably, there were improvements in social communication (MD = -4.96, 95% CI [-7.49, -2.44]), irritability (MD = -2.38, 95% CI [-4.06, -0.71]), hyperactivity (MD = -4.03, 95% CI [-6.17, -1.89]), and different word usage skills (MD = 20.48, 95% CI [7.41, 33.55]). However, social awareness (MD = -1.63, 95% CI [-4.07, 0.81]), social cognition (MD = -3.60, 95% CI [-9.36, 2.17]), social mannerisms (MD = -0.73, 95% CI [-2.55, 1.09]), social motivation (MD = -1.21, 95% CI [-2.56, 0.13]), lethargy (MD = -1.12, 95% CI [-3.92, 1.68]), and stereotypical behaviors (MD = -0.23, 95% CI [-1.27, 0.80]) did not significantly improve. The study demonstrates the potential of AAAT in improving certain core symptoms of ASD, such as social communication, irritability, hyperactivity, and word usage skills. However, the effectiveness of AAAT in other ASD symptom domains remains uncertain. The research is limited by the absence of long-term follow-up data and a high risk of bias in existing studies. Therefore, while the findings indicate the promise of AAAT in specific areas, caution is advised in generalizing its efficacy across all ASD symptoms.