1. Aragão GF, Brandão CB, Júnior JEL. Cannabidiol in autism: Clinical pharmacology priorities for trial design. Br J Clin Pharmacol. 2025.

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2. Hetta HF, Alanazi FE, Alqifari SF, Ali MAS, Albalwi MA, Albalawi AA, Ramadan YN. The Gut-Brain Axis in Autism: Inflammatory Mechanisms, Molecular Insights, and Emerging Microbiome-Based Therapies. Mol Neurobiol. 2025; 63(1): 211.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiology, including genetic, environmental, and microbial influences. Recent studies have highlighted the gut-brain axis as a crucial mediator in ASD pathophysiology, linking alterations in gut microbiota to neurodevelopmental and behavioral abnormalities. Individuals with ASD frequently exhibit dysbiosis, characterized by an imbalance in gut microbial composition, reduced microbial diversity, and increased intestinal permeability. These changes contribute to systemic inflammation, altered neurotransmitter synthesis, and metabolic dysfunctions, ultimately impacting brain function. Emerging therapeutic approaches targeting gut microbiome, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), have shown potential in alleviating both gastrointestinal (GI) and ASD-related symptoms. This review explores the latest evidence on microbiome alterations in ASD, the mechanisms by which gut dysbiosis influences neurodevelopment, and the therapeutic potential of microbiome-based interventions. Understanding these connections may open new avenues for targeted treatments in ASD management.

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3. Li H, Du M, Ru X, Liu J, Liu L, Zhang S, Xu Y, Xie Z. Comparison of different propofol target-controlled infusion concentrations in children with autism spectrum disorder undergoing magnetic resonance imaging. Sci Rep. 2025; 15(1): 42706.

This study aimed to compare the safety and efficacy of two target-controlled infusion (TCI) concentrations of propofol for sedation during cranial functional magnetic resonance imaging (fMRI) in children with autism spectrum disorder (ASD). A total of 120 preschool children with ASD scheduled for fMRI between January 2021 and July 2023 were enrolled and randomized into two groups: a low-concentration group (2.0 µg/mL, n = 60) and a high-concentration group (2.5 µg/mL, n = 60). Vital signs, sedation parameters, and adverse events were meticulously recorded to assess outcomes. The first-time sedation success rate was high and comparable between the 2.0 group and the 2.5 group (91.67% vs. 96.67%, p = 0.439). However, the 2.5 group demonstrated a significant reduction in mean systolic blood pressure (p = 0.001). While the overall incidence of adverse events was not significantly different, respiratory and circulatory depression events were less frequent in the 2.0 group. Furthermore, the 2.0 group required a significantly lower maintenance dose of propofol (p < 0.001), experienced a shorter recovery time (p = 0.042), and had a smoother emergence profile. In conclusion, a propofol TCI concentration of 2.0 µg/mL is effective and safe for fMRI sedation in children with ASD and is clinically preferable to 2.5 µg/mL due to a more stable hemodynamic profile, reduced drug requirement, and faster, smoother recovery.Trial registration: ChiCTR2100050071.

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4. Liu Y, Xia M, Zhang X, Luo J, Liu T, Gong H, Liu J, Chen M, Wang L, Zhao J, Gong M, Luo Y, Fan X. Naringin Alleviates Autistic-Like Behaviors in BTBR Mice Through Cannabinoid Receptor Type 1-Mediated Restoration of Hippocampal Neurogenesis. CNS Neurosci Ther. 2025; 31(12): e70654.

BACKGROUND: Naringin, a flavanone glycoside (naringenin 7-O-neohesperidose), exhibits a broad range of pharmacological activities, including neuroprotection. However, its effects on autistic-like behavior have not been extensively studied. METHODS: In this investigation, we utilized the autistic BTBR T + tf/J (BTBR) mice to conduct behavioral tests assessing autistic-like phenotypes. We evaluated hippocampal neurogenesis through immunofluorescence and employed molecular biological techniques, along with RNA sequencing, to elucidate the underlying molecular mechanisms. RESULTS: Our findings revealed that the administration of naringin alleviated autism-associated behaviors in BTBR mice. RNA sequencing analysis indicated that naringin facilitated the recovery of impaired hippocampal neurogenesis in these mice, as evidenced by an increase in doublecortin (DCX)-positive cells and neuronal progenitor cells (NPCs) in the dentate gyrus (DG). Furthermore, we confirmed that the cannabinoid receptor type-1 (CB1) plays a role in the therapeutic effects of naringin. CONCLUSIONS: This research highlights the potential of naringin as a promising treatment option for autism spectrum disorder (ASD) and suggests that targeting hippocampal neurogenesis through the CB1 receptor may be an effective strategy.

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5. McLaughlin J, Crocetti D, Mostofsky SH, Lidstone DE. Anomalous Pattern of Left Hemisphere Visual Connectivity in Children With Autism: Association With Impaired Praxis. Autism Res. 2025.

Prominent theories of autism suggest autism-associated differences in visual-motor integration (VMI) may disrupt learning of motor and social skills typically acquired by observation and imitation. Supporting these theories, children with autism spectrum disorder (ASD) show robust differences in motor tasks reliant on dynamic VMI (e.g., ball-catching and motor imitation) and anomalous visual-motor connectivity between higher-order visual (HOV) and sensory-motor cortices. Use of functional MRI (fMRI) to examine HOV functional connectivity (FC) has been particularly revealing with other conditions. For instance, research with congenitally blind adults reveals a particular pattern of altered HOV connectivity, showing reduced HOV connectivity with primary sensory-motor (SM1) and primary auditory (A1) cortices yet « compensatory » increased connectivity between HOV and prefrontal cortex (PFC). Informed by these findings, we used fMRI to examine HOV FC in children with ASD, hypothesizing they would show a distinct pattern of HOV connectivity relative to typically developing (TD) children, with decreased HOV-SM1 connectivity and increased « compensatory » HOV-PFC connectivity. We further hypothesized that this altered pattern of HOV connectivity would correlate with autism-associated difficulties with performing skilled actions (« praxis »), often learned through visual imitation. Our findings suggest ASD children show an altered pattern of HOV connectivity that is characterized by reduced HOV connectivity with SM1 yet increased connectivity with PFC. Further, this HOV connectivity correlated with impaired praxis in children with ASD, suggesting that altered patterns of HOV connectivity may contribute to difficulty acquiring a range of skilled behaviors observed in autism.

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6. Reuter MS, Salazar NB, Howe JL, Hoang N, Sarikaya E, Selvanayagam T, Mendes de Aquino M, Vicente AM, Oliveira G, Freitag CM, Thiruvahindrapuram B, Trost B, Scherer SW. UBR5 loss-of-function variants in autism spectrum disorder and intellectual disability: case series and review of the literature. NPJ Genom Med. 2025.

UBR5 encodes an E3 ubiquitin-protein ligase which targets distinct N-terminal residues of proteins for degradation. Heterozygous loss-of-function variants were reported in patients with Autism Spectrum Disorder (ASD) and developmental delay, and recently in a cohort of individuals with neurodevelopmental disorders and variable other features. Here, we report three unrelated individuals with de novo loss-of-function variants in UBR5, presenting with ASD and intellectual disability. We review the literature for other de novo predicted loss-of-function variants in probands with ASD or developmental delay (in total n = 11 variants), providing further evidence that UBR5 haploinsufficiency is associated with ASD and atypical neurodevelopmental trajectories, including developmental delay and intellectual disability.

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7. Ricci C, Midroit MJ, Caicci F, Achsel T, Domínguez-Iturza N, Bagni C. CYFIP1 governs the development of cortical axons by modulating calcium availability. Nat Commun. 2025; 16(1): 10764.

The human CYFIP1 gene is linked to Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ), both associated with brain connectivity defects and corpus callosum abnormalities. Previous studies demonstrated that Cyfip1-heterozygous mice exhibit diminished bilateral functional connectivity and callosal defects-resembling observations in ASD and SCZ patients. Here, we demonstrate that CYFIP1 is crucial for cortical axonal development and identify insufficient calcium uptake as the pivotal mechanism. In vivo, Cyfip1 heterozygosity delays callosal axon growth and arborization. Additionally, Cyfip1-deficient cortical neurons and axons have reduced intracellular calcium, along with impaired mitochondria morphology, activity, and motility. Mechanistically, CYFIP1 binds and stabilises the mRNA of specific voltage-gated calcium channel subunits, explaining the decreased calcium concentration in Cyfip1(+/-) cells. Notably, elevating intracellular calcium rescues delayed axonal growth and mitochondrial defects in Cyfip1-deficient neurons. These findings highlight that, by regulating mRNA metabolism, CYFIP1 ensures proper callosal development, offering insights into brain connectivity disruptions underlaying neurodevelopmental disorders.

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8. Rouphael M, Bitar T, Alarcan H, Gerges P, Sacre Y, Andres CR, Hleihel W. Exploration of Homocysteine Metabolism and Genetics in Autism Spectrum Disorder. Nutrients. 2025; 17(23).

BACKGROUND: Understanding the genetic and metabolic profiles of individuals diagnosed with Autism Spectrum Disorder (ASD) is important for clarifying the biological characteristics of this complex disorder. OBJECTIVES: Given the limited data available for the Lebanese population, this case-control study aimed to investigate the association between common MTHFR variants and ASD risk and to examine differences in homocysteine metabolism between Lebanese individuals with ASD and neurotypical controls. METHODS: From June 2022 to June 2023, 86 individuals with ASD and 86 controls matched for age and sex were recruited. Genotyping of the rs1801133 and rs1801131 variants and biochemical measurements were performed, followed by comparative statistical analyses. RESULTS: Our results showed no significant association between the rs1801133 or rs1801131 variants and ASD risk (p > 0.05). However, the sample size was not sufficient to rule out small genetic effects. Metabolic analyses revealed significantly higher homocysteine concentrations and lower vitamin B9 levels in the ASD group (p < 0.0001), while vitamin B12, fasting glucose, and lipid profiles did not differ significantly between groups (p > 0.05). Among individuals with ASD, the TT genotype of rs1801133 was associated with elevated homocysteine concentrations (OR = 9.10, p = 0.014), whereas neither MTHFR variant was associated with vitamin B12 or B9 levels in ASD or control participants. CONCLUSIONS: Future research directions could focus on exploring the role of key enzymes associated with hyperhomocysteinemia in individuals with ASD and on replicating these preliminary findings in larger, adequately powered cohorts.

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9. Sadeh H, Razi T, Arbel R, Netzer D, Meiri G. Medical Cannabis Use in Autism: Insights from an Israeli HMO on Patient Characteristics and Alignment with National Guidelines. J Child Adolesc Psychopharmacol. 2025.

Objective: Evidence for medical cannabis use and effectiveness in autism has begun to accumulate but remains limited, even as clinical interest has rapidly increased. In Israel, medical cannabis may be prescribed for autism with severe behavioral disturbances under strict Ministry of Health criteria requiring prior trials of two Food and Drug Administration (FDA)-approved antipsychotics. Using a large real-world dataset, this study aimed to characterize autistic individuals prescribed medical cannabis and evaluate adherence to national guidelines. Methods: A retrospective cohort study was conducted using electronic medical records from Clalit Health Services, Israel’s largest Health Maintenance Organization. All individuals with a documented autism diagnosis between 1990 and 2025 were identified (N = 36,610) and classified as cannabis-prescribed (N = 462) or not-prescribed (N = 36,148). Demographic and clinical characteristics were compared, including prior use of FDA-approved antipsychotics. Results: Only 1.2% of individuals with autism were prescribed medical cannabis. Of these, 4.3% of prescriptions were issued for children under 5 years of age. The cannabis-prescribed group was diagnosed earlier (median 3 vs. 5 years, p < 0.001) and had higher rates of ADHD (42% vs. 30%), intellectual disability (12% vs. 5%), and epilepsy (14% vs. 6%) (all p < 0.001). While 69% had used at least one FDA-approved antipsychotic medication prior to cannabis initiation, only 28% had documented trials of both, as required by national guidelines. Marked sociodemographic disparities were also observed: the cannabis-prescribed group had a higher socioeconomic status (median SES 7 vs. 6, p < 0.001) and lower representation of Arab individuals (2.7% vs. 11%, p < 0.001). Conclusions: Medical cannabis use among autistic individuals was rare and mainly observed among those with more complex clinical profiles and higher socioeconomic backgrounds. Most prescriptions did not fully comply with guidelines requiring prior antipsychotic trials. These findings underscore the need for enhanced regulatory oversight, equitable access, and longitudinal research to evaluate real-world outcomes and guide evidence-based clinical practice.

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10. Saduakassova K, Kassenova G, Issayeva R. EPIDEMIOLOGY AND DIAGNOSTIC CHALLENGES OF AUTISM SPECTRUM DISORDERS IN CHILDREN IN THE REPUBLIC OF KAZAKHSTAN. Georgian Med News. 2025; (366): 41-6.

OBJECTIVE OF THE STUDY: To assess the prevalence of autism spectrum disorders (ASD) among children in Kazakhstan, the availability of psychiatric and correctional care, and to identify barriers to diagnosis and treatment. MATERIALS AND METHODS: The data from the statistical collection « Psychiatric Care to the Population of the Republic of Kazakhstan » (2015-2023) and the results of an online survey of 188 parents of children with ASD, conducted in 2021 through public organizations in 29 cities/towns, were analyzed. Descriptive statistics, chi-square test, Mann-Whitney test, and logistic regression were used. RESULTS: In 2023, the number of psychiatrists was 0.4 per 10,000 population, psychotherapists – 0.01. The contingent of children with ASD increased from 8.6 (2015) to 161.3 per 100 thousand children aged 0-17 years (2023), primary incidence – from 4.3 to 33.6 per 100 thousand (2015-2022). The survey revealed that 81.4% of children receive correction, but ABA therapy is available to only 4.3% of them. The average age of diagnosis is 2.5 years, and 79.8% of parents have low awareness-the main barriers are a shortage of specialists, high cost of services, and stigmatization. CONCLUSIONS: Low detection rates of ASD (compared to the US – 3220 per 100,000, South Korea – 2640) are due to a lack of screening, shortage of specialists, and low awareness. The study highlights the unique challenges of Central Asia, where a lack of data and resources hinders diagnosis and support. A national program of screening, training of specialists, and subsidizing of ABA therapy is needed. The work holds international importance for countries with transition economies, particularly in Central Asia, where similar problems necessitate systemic solutions.

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11. Vidal-Zaborski O, Merino D, Fernandez A, Mercery M, Herbreteau L, Askenazy F, Zuluaga MA, Ismailova E, Douet-Vannucci V, Thümmler S. Autonomic and hormonal biomarkers in individuals with autism spectrum disorders and developmental or intellectual delay: A systematic PRISMA review. Neurosci Biobehav Rev. 2025; 180: 106496.

BACKGROUND: Individuals with autism spectrum disorder (ASD) and co-occurring global developmental delay or intellectual disability (GDD-ID) are highly vulnerable to stress, but a very small amount of research is being conducted at the physiological level. This review aims to identify and synthesize studies examining autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in such populations. METHODS: The review followed PRISMA 2020 guidelines (Pages et al., 2021) and the inclusion criteria encompassed peer-reviewed studies published in English that reported direct physiological biomarker measurements (e.g., heart rate variability, electrodermal activity, cortisol) in individuals with ASD and documented GDD-ID (IQ < 75 and/or developmental delay). Exclusion criteria included studies involving animals, pharmacological interventions, or solely behavioural outcomes. The literature search was conducted across four databases: PubMed, Scopus, Web of Science, and OpenAlex (last search: April 2025). Two reviewers independently screened publications, assessed bias (JBI) and evaluated the certainty (GRADE). No meta-analysis was performed due to high heterogeneity. The protocol was registered on PROSPERO (CRD420251025329). RESULTS: Thirty-four studies (n ≈ 1160 individuals with ASD; mean age: 10.7 years) were included. ANS studies reported that ASD individuals had a sympathetic hyperactivation, a reduced parasympathetic tone (low respiratory sinus arrhythmia), and a delayed recovery after stress. HPA findings were mixed, showing both hypoactivation (low cortisol) and feedback dysfunction (e.g., Dexamethasone non-suppression) in those individuals. Respiratory sinus arrhythmia (RSA) was positively associated with social adaptation. Age-related physiological maturation appeared atypical. ASD's symptom severity was more consistently positively associated with physiological profiles than IQ. LIMITATIONS: Clear evidence was limited since most studies had low certainty due to small sample sizes, variability and heterogeneity in methods, populations, and task relevance. Only few recent studies targeted ASD-GDD-ID profiles. CONCLUSION: Individuals with ASD and GDD-ID exhibit autonomic hyperarousal and altered HPA regulation, suggesting reduced physiological flexibility. However, strong discrepancies exist among studies, and hereby, more inclusive and adapted protocols are needed to better characterise this physiological profile.

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12. Yahia S, El-Gilany AH, Magdy RM, Bebars GM, Fadle YS, Dawoud H, NS EL, Moussa MM, Assy R, Sadek AA, Abdelmoneim Z. A multicenter study on clinico-epidemiological profile of phenylketonuria in Egyptian children. Sci Rep. 2025; 15(1): 42928.

Phenylketonuria is the most common heritable metabolic disorder. Early detection through newborn screening and proper nutritional management are essential for preventing neurodevelopmental complications. This study aims to describe the epidemiological profile of PKU in Egypt, assess the impact of early diagnosis, and examine the relationship between dietary adherence and comorbidities, including developmental and growth impairment. This is a multicenter retrospective cross-sectional study conducted in four university hospitals in Egypt between January 2024 and January 2025. A total of 365 patients with PKU aged 0-18 years were included. Data on demographics, phenotype classification, complications, and diet adherence were collected. We found that the most common PKU phenotype was classic PKU (36.3%). Early diagnosis through NBS was reported in 67.7%, and dietary adherence in 79.5%. Developmental delay was significantly lower in early-diagnosed children (3.2%) than in late-diagnosed children (100%). BH4 deficiency (1.6%) was associated with developmental delay and epilepsy despite early diagnosis. Diet adherence was linked to lower phenylalanine levels and fewer complications. Neurodevelopmental problems in PKU were decreased by the national NBS program. Better results depend on early diagnosis, diet adherence, and awareness of BH4 deficiency. Diet non-adherence not only worsens neurodevelopmental outcomes but also negatively affects growth parameters in these children.

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13. Zheng Y, Ma S, Liu X, Wang L, Chen M, Yuan J, Wang H. Deep neural networks and deep deterministic policy gradient for early ASD diagnosis and personalized intervention in children. Sci Rep. 2025; 15(1): 42648.

Early diagnosis and personalized intervention for Autism Spectrum Disorder (ASD) in children can potentially improve developmental outcomes, though current methods often lack scalability and adaptability. This study introduces an integrated system combining a deep neural network (DNN) and a Deep Deterministic Policy Gradient (DDPG) reinforcement learning framework for early ASD detection and adaptive psychosocial intervention. The DNN, trained and validated on diverse datasets spanning toddlers to adolescents (sourced from the University of Arkansas, Vaishnavi Sirigiri, and Afarin Bargrizan), achieved a predictive accuracy of 96.98% with precision (97.65%), recall (96.74%), and ROC AUC (99.75%) on the test sets, demonstrating superior performance compared to traditional models like Random Forest and Logistic Regression. Key features, such as Qchat-10-Score and ethnicity, were identified using multi-strategy selection (LASSO, Random Forest). Building on these predictions, the DDPG-based intervention system simulated personalized strategies over 12 monthly cycles using virtual data to optimize intervention type, frequency, and intensity, resulting in observed improvements of up to 25% in social skills, up to 30% reduction in behavioral issues, and up to 20% improvement in emotional stability, with a reduction in high-risk ASD cases from 65 to 25% in the simulated cohort. This system offers a promising, data-driven approach to ASD management, enhancing early screening and tailoring interventions to individual needs.

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14. Zhu M, Liu J, Xiao H, Shi F, Li K, Tao L. Measurement properties of assessment tools for affiliate stigma in parents of children with autism: a systematic review protocol. BMJ Open. 2025; 15(11): e111592.

INTRODUCTION: Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder. Parents of children with ASD often have a higher level of affiliate stigma, which impacts their physical and mental health, family relationships and social functions. Nowadays, a variety of assessment tools are available for measuring this stigma, but they have many limitations. This systematic review aims to critically appraise the measurement properties of instruments used to assess affiliate stigma in parents of children with autism and help researchers and healthcare professionals make more appropriate choices when using these tools. METHODS AND ANALYSIS: This protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search five English databases (ie, PubMed, Web of Science, ScienceDirect Online, Embase and Cochrane Library) and four Chinese databases (ie, SinoMed, China National Knowledge Infrastructure, Wanfang Database and VIP information) from the databases’ inception to 30 September 2025. Eligible studies will evaluate instruments measuring affiliate stigma in parents of children with autism, including self-report and observer ratings. The psychometric properties assessed will include reliability, validity, responsiveness, interpretability and clinical utility. Only primary quantitative studies published in peer-reviewed journals will be included. The search will have no limitations on language or time. Two researchers will independently carry out data extraction and quality assessment, with disagreements resolved through consensus or a third researcher. The consensus-based standards for the selection of health measurement instruments risk of bias checklist and the Grading of Recommendations Assessment, Development and Evaluation approach will be used to evaluate each measure’s methodological quality and overall strength of evidence. ETHICS AND DISSEMINATION: As this research constitutes a systematic review of pre-existing published data, formal ethics committee approval is deemed unnecessary in accordance with international research ethics guidelines. The synthesised findings will be submitted for publication in a rigorously peer-reviewed academic journal and presented at pertinent scientific conferences to ensure transparent knowledge dissemination within the academic community. PROSPERO REGISTRATION NUMBER: CRD420251043478.

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