1. Albekairi TH, Albakheet AS, Alosaimi TH, Bakheet SA, Nadeem A, Attia SM, Ansari MA, Hussein MH, Mahmoud MA, Ahmad SF. Ursolic acid enhances social behavior and modulates Th1, Th17, and T regulatory cell-related transcription factor signaling in the BTBR T(+) Itpr3(tf)/J mouse model of autism. J Neuroimmunol. 2025; 410: 578810.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by unusual social interactions, limited speech, and repetitive behaviors or hobbies. The BTBR T(+) Itpr3(tf/)J (BTBR) inbred mice are commonly used as a model for ASD because they display many genetic traits associated with autism. Ursolic acid, a naturally occurring compound found in several plants, has shown promise as a treatment for various inflammatory disorders and related experimental models. This study aimed to explore the potential effects of ursolic acid on self-grooming, marble burying, and social behaviors in BTBR mice. We examined how ursolic acid affects the expression of Th1 (IFN-γ, TNF-α, STAT1, STAT4, and T-bet), Th17 (IL-17, RORγt, and STAT3), and T regulatory (Treg; IL-10, TGF-β1, and Foxp3) markers in CD4(+) T cells within the spleens of BTBR and C57BL/6 mice. Additionally, we assessed the impact of ursolic acid on brain mRNA levels of IFN-γ, TNF-α, STAT1, STAT4, T-bet, IL-17, RORγ, STAT3, IL-10, TGF-β1, and Foxp3. Treatment with ursolic acid significantly affected behavioral issues in BTBR mice. In these animals, ursolic acid reduced the levels of Th1 and Th17 cells while increasing the levels of Treg cells. Furthermore, it decreased the expression of Th1 and Th17 mRNA and increased the expression of Treg-related mRNA in the brain. Our findings suggest that, due to its anti-inflammatory properties, ursolic acid may be a beneficial treatment for behavioral impairments in BTBR mice.

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2. Alessandri-Bonetti A, Guglielmi F, Faustini A, Sangalli L, Staderini E, Gallenzi P. Prevalence of OSA Risk and Bruxism in Children With Autism Spectrum Disorders. Autism Res. 2025.

Children with autism spectrum disorder (ASD) often present with sleep disorders, including obstructive sleep apnea (OSA), a condition characterized by upper airway obstruction during sleep. Bruxism has been recently described as being associated with OSA. This study aimed to assess the prevalence of OSA risk and bruxism in pediatric ASD patients compared to age and sex-matched healthy controls using the validated screening tool Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (SRBD-PSQ). Fifty-eight consecutive pediatric ASD patients were screened for OSA and bruxism at the Dentistry Unit of A. Gemelli Policlinic and compared to 58 healthy patients using chi-square tests. Comparison between the two groups was repeated by controlling for body mass index (BMI) and behavioral symptoms with ANCOVA and logistic regression analyses. Of 58 ASD patients (10.3 ± 3.3 y/o, 74.5% males), 60.3% presented with an increased OSA risk, compared to 13.8% in the controls (p < 0.001, OR = 3.682, 95% CI: 1.933, 7.012). After controlling for BMI (which was significantly higher among ASD patients), those with ASD had significantly higher odds of OSA risk compared to controls (OR = 9.6, 95% CI: 3.56, 26.21). After controlling for the SRBD-PSQ behavioral component, the association between ASD and OSA risk lost its significant difference (p < 0.862). No significant difference was found between ASD patients and controls in awake (3.6% vs. 6.9%, p = 0.680) and sleep (25.5% vs. 32.8%, p = 0.393) bruxism. Pediatric patients with ASD present at higher risk of OSA, most likely explained by the behavioral symptoms; self-reported bruxism did not significantly differ compared to healthy controls. Children with autism spectrum disorder present a higher risk of suffering from obstructive sleep apnea according to the Sleep‐Related Breathing Disorder scale of the Pediatric Sleep Questionnaire; however this result could be explained by the behavioral symptoms. Children with autism spectrum disorder do not report higher awake and/or sleep bruxism compared to peers without autism. eng.

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3. Banjar MA, Sulaimani MF, Bagadood NH. A qualitative study on the effectiveness of naturalistic developmental behavioral interventions for children with autism Spectrum disorder in Saudi Arabia. Acta Psychol (Amst). 2025; 261: 105968.

This qualitative study explored the implementation of Naturalistic Developmental Behavioral Interventions (NDBIs) as an early intervention strategy for children with autism spectrum disorder (ASD) in Saudi Arabia, drawing on the perspectives of certified Applied Behavior Analysis (ABA) specialists. Data were collected through semi-structured interviews with five licensed practitioners, four based in Riyadh and one in Jeddah, who hold credentials from the Behavior Analyst Certification Board (BACB). The findings illuminate participants’ conceptual understanding of NDBIs, their motivations for adopting these interventions, and the mechanisms employed in their application. Additionally, the study identified several barriers impeding effective implementation, including insufficient specialist training, limited administrative support, logistical challenges, and family-related constraints. Based on these insights, the study recommends expanding practical training for ABA specialists, increasing community awareness of NDBIs, and ensuring ongoing supervision by experienced professionals. The findings underscore the need for further empirical studies on the application of NDBIs within culturally specific contexts, particularly in Arab settings, to promote more inclusive and effective early intervention services.

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4. Berry-Kravis E, Hagerman R, Cohen J, Budimirovic D, Buchanan CB, Silove N, Tich N, Thibodeau A, Dobbins T, Sebree T, O’Quinn S, Albers DS, Bzdek KG, Nomikos G, Budur K. Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study. J Neurodev Disord. 2025; 17(1): 69.

BACKGROUND: Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS. DESIGN: ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS. METHODS: Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C(FXS) SA and ABC-C(FXS) Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child’s overall behavior. RESULTS: At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C(FXS) SA, ABC-C(FXS) Irr, and CaGI-C scores. CONCLUSIONS: Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS. TRIAL REGISTRATION: ZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018.

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5. Bertollo JR, Fok M, Martino DC, DeLucia EA, Bunis M, Scarpa A. Autism Assessment From Home: Piloting a Brief, Remote Autism Observation for Children. J Autism Dev Disord. 2025.

PURPOSE: Since COVID-19, tele-based methods of autism assessment have been relied upon to a previously unparalleled degree; however, the need for such advancements is not new. Observation-based measures are a crucial component of face-to-face autism diagnostic evaluations, but few validated observation tools exist for remotely assessing autism across childhood, offering minimal guidance for older children and adolescents. Sanchez and Constantino (Develop Med Child Neurol, 62(7): 806-812, 2020) previously validated a brief, face-to-face, clinician-facilitated observation coded according to the Childhood Autism Rating Scale, Second Edition (CARS-2). During the pandemic, this measure was adapted as a remote observation, but has yet to be validated in this format. METHODS: The current study validated this remote observation against the in-person Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), in a sample of 30 children ages 1-16 years (M = 7.25, SD = 4.05). RESULTS: The remote observation was highly correlated with the ADOS-2 (r = .75, p < .001) and Social Responsiveness Scale, Second Edition (r = .74, p < .001), and demonstrated acceptable sensitivity (88.9%) and specificity (80%) in predicting research diagnostic classification. The remote observation correctly predicted whether a child met criteria for a research diagnosis of autism in 82.8% of cases, and the same classification as the ADOS-2 in 72.4% of cases. CONCLUSIONS: This pilot study offers preliminary support for the validity of this brief, accessible, remote autism observation. This is a crucial step in ensuring uniform training and clinical procedures for tele-assessment of autism, to help mitigate long-standing barriers to service access (e.g., geography, cost, availability).

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6. Bridges M, Secchi A, Whiskey E, Shergill S. A multidisciplinary approach to establishing clozapine in a patient with schizophrenia and comorbid ASD: a case report. BMC Psychiatry. 2025.

BACKGROUND: There is substantial symptom overlap in psychosis and autism spectrum disorder (ASD) and co-morbidity is common. In addition, antipsychotic response may be moderated by the co-occurrence. Individuals with ASD may be at greater risk of some clozapine adverse effects and occasionally, its use may be contra-indicated. CASE PRESENTATION: We present the case of a patient with ASD with psychosis unresponsive to multiple antipsychotics, but extra precaution was required with clozapine. CONCLUSION: A multidisciplinary approach is required to establish clozapine in a patient with schizophrenia and ASD.

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7. Bruno JL, Plank JR, Leder S, Lake EMR, Finn ES, Green T. Transdiagnostic similarities and distinctions in brain networks associated with autistic social impairments: a prospective cohort study. Mol Autism. 2025; 16(1): 56.

BACKGROUND: Despite high rates of autism spectrum disorder (ASD), understanding of pathophysiology is limited. The RAS-mitogen-activated protein kinase (RAS-MAPK) pathway plays a crucial role in ASD and is altered in children with Noonan syndrome (NS). Children with NS offer a unique model to disentangle genetic and neurological underpinnings of ASD. METHODS: This study aimed to examine functional brain network anatomy underlying social impairments in children with NS (n = 28, mean age = 8.24), and tested generalizability of models developed in a non-syndromic cohort enriched for ASD (Autism Brain Imaging Data Exchange (ABIDE), n = 352, mean age = 11.0). Connectome-based predictive modeling (CPM) was applied to fMRI data to predict the severity of autism symptoms, indexed by the Social Responsive Scale (SRS), in children with NS. Next, we tested if a model developed to predict autism symptoms in an autism-enriched sample of children without NS (ABIDE) could predict autism symptoms in children with NS. RESULTS: Predicted SRS scores were significantly associated with observed SRS scores in NS (r(s) = 0.43, p = 0.011). Application of the predictive model generated in the autism-enriched cohort (ABIDE) significantly predicted observed SRS scores in NS (r(s) = 0.46, p = 0.018). Predictive brain networks in both NS and the non-syndromic cohorts included subcortical-cerebellar networks and visual processing networks. LIMITATIONS: The size of our NS cohort is small, given the rarity of NS. However, the significant cross-dataset comparison yielded in this study suggests that use of large publicly available datasets can be useful in contextualizing smaller and harder to collect datasets in rare genetic syndromes. CONCLUSIONS: The presence of shared brain networks suggests converging patterns of functional connectivity underlying autism symptoms across diagnoses. These findings point to potential overlap between non-syndromic autism and NS and highlight the value of human genetic models for studying ASD. Future work investigating RAS-MAPK pathway dysregulation may further elucidate its contribution to autism-related brain function.

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8. Chen H, Zhang X, Chen Z, Ren Y, Liu R. Auxiliary diagnostic method for children with autism spectrum disorder based on virtual reality and eye-tracking technology. Sci Rep. 2025; 15(1): 40552.

In the behavioral analysis of children with Autism Spectrum Disorder (ASD), virtual reality (VR)-based eye-tracking technology offers a precise method for assessing social and cognitive characteristics. It overcomes the limitations of traditional diagnostic methods, such as clinician subjectivity and experience bias. VR also addresses ASD-related challenges like attention instability and emotional variability during social interactions. This paper combines eye-tracking with VR environments to analyze gaze patterns in children with ASD. It proposes a new diagnostic framework to improve objectivity and accuracy.The gaze estimation model integrates head and eye movement data to predict gaze direction. It enhances precision using binocular fusion and employs multi-scale convolutional kernels to extract hierarchical eye movement features. The model simplifies network connections to retain essential information. A lightweight Transformer architecture models long-range temporal dependencies in eye movements. A Bayesian decision model is used to classify fixations, saccades, and smooth pursuit.To test the model, an emotion recognition task was designed in a WebVR environment. Gaze data from children with ASD were collected, key features were extracted, and abnormal patterns were identified for diagnostic support. The experimental results showed an 85.88% accuracy rate. This confirms the effectiveness of combining VR and eye-tracking technology in ASD diagnosis, advancing intelligent medical tools, and reducing reliance on subjective clinical judgment.

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9. Conrad CE, George C, Færk E, Jakobsen H, Thomsen PH, Lauritsen MB. Attachment and reflective functioning in families with a child on the autism spectrum. Front Psychol. 2025; 16: 1651408.

The concepts of attachment and reflective functioning are predictors of positive development in children on the autism spectrum. This is the one of the first cross-sectional studies to examine associations between parents’ attachment representations and parental reflective functioning and child attachment in families with children on the autism spectrum. Twenty-eight parents completed the Adult Attachment Projective Picture System and questionnaires of Maternal Perception of Child Attachment and Parental Reflective Functioning regarding their child on the autism spectrum and when applicable a typically developing sibling. To test any associations between the parents’ attachment and parental reflective functioning and parents’ perception of child attachment, the sample was divided in organized (secure, dismissing and preoccupied combined) as compared with unresolved parents. We found a higher level of the parents’ Interest and Curiosity in their child’s mental states (a parental reflective functioning domain) in the organized as compared with unresolved parents. Also, mothers had significantly higher levels of Interest and Curiosity than fathers. There were no other significant differences regarding the remaining questionnaire domains. Also, there were no significant differences between parents’ rating of child attachment or parental reflective functioning in relation to their child on the autism spectrum compared with their typically developing sibling. The findings suggest that future support may enhance focus on parents unresolved to loss and trauma and fathers. Also, more research is needed to understand the implications of attachment and reflective functioning in families affected by autism.

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10. Das MR, Rahman M, Zhou C. Structural Insights into Protein Mutations Related to Autism Spectrum Disorders: A Systematic Review. ACS Chem Neurosci. 2025; 16(22): 4341-50.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental condition characterized by difficulties in social interactions and communication, alongside repetitive behaviors and restricted interests. Its etiology is a complex etiology involving genetic, environmental, and epigenetic factors, with significant contributions from mutations in synaptic proteins, including neuroligins (NLGNs), neurexins (NRXNs), and SHANK family proteins. Structural changes caused by mutations in these proteins can lead to synaptic dysfunction, disrupt scaffolding, and impact neuronal circuitry, which reflects the symptoms of ASD. The purpose of this study is to compile the most recent findings regarding protein structure and how specific mutations in these proteins contribute to ASD. This systematic review conducted a comprehensive analysis of research published from 2014 to 2024, collected from the Web of Science and Scopus databases, and the protein structure was collected from the Protein Data Bank. Research that employed cryogenic electron microscopy, nuclear magnetic resonance spectroscopy, and other advanced structural biology methods for molecular modeling was prioritized. After evaluating the findings of the final 40 studies, mutations in the synaptic proteins SHANK3 (G54W, L47P, G250D, R12C, L68P), SHANK2 (S557N), NLGN3 (R451C), NLGN4 (R101Q), and NRXN1 destabilize protein structure, reduce synaptic adhesion, and disrupt neurotransmitter clustering, which influences ASD symptoms. Advanced techniques reveal the molecular structure underlying ASD in animal models, which provides interventions like gene transplantation that can mitigate the effects of these mutations. However, challenges persist in finding treatments for the numerous molecular mechanisms contributing to ASD, emphasizing the need for further research into the structure of all ASD-related proteins.

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11. Dayley EE, Durham S, Palumbo MC, Lundell JF, Freeman SM. Oxytocin receptor gene expression in the basal forebrain in autism: association with receptor binding levels and single nucleotide polymorphisms. Res Sq. 2025.

BACKGROUND: The brain’s oxytocin system has been implicated in the neurobiology of autism (ASD), given the role of oxytocin in modulating social function in humans and animals more broadly. Previous work from members of our group reported dysregulation in oxytocin receptor (OXTR) binding in postmortem tissue from the basal forebrain in donors with autism compared to unaffected control donors. This study follows up on those findings by investigating the potential genetic and gene expression changes that could be driving those differences. METHODS: We used adjacent sections from the same specimens from our previous study and performed duplex fluorescent in situ hybridization to visualize and quantify OXTR mRNA in the ventral pallidum (VP) and in the cholinergic magnocellular neurons of the nucleus basalis of Meynert (NBM), visualized with choline acetyltransferase (ChAT). We genotyped the brain samples using a SNP microarray on extracted DNA. We then used regression models to test associations between OXTR binding density, OXTR mRNA levels, and relevant OXTR SNPs. Additionally, we tested for correlation between age and OXTR mRNA. RESULTS: ASD specimens showed significantly greater OXTR mRNA than unaffected donors in both the VP and the NBM. Furthermore, this is the first demonstration of OXTRexpression in the cholinergic neurons of the human basal forebrain; 73% of OXTR signal in the images of the ChAT+ neurons were colocalized with the cholinergic neurons. OXTR binding levels from our previous study were positively associated with OXTR mRNA in the NBM of control specimens but not in ASD specimens, implying potential dysregulation at the level of protein translation or mRNA trafficking in the NBM in ASD. OXTR binding levels were not associated with OXTRmRNA in the VP of either group. We genotyped all specimens for three common SNPs in the OXTR gene that have been associated with ASD in the literature, but none significantly predicted levels of OXTR binding or gene expression in the NBM or VP. CONCLUSIONS: Taken together, our results contribute to a more nuanced picture triangulating variation in OXTR gene sequence, gene expression, protein levels, and human behavior. TRIAL REGISTRATION: Clinical trial number: not applicable.

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12. Ding Y, Zhang H, Qiu T. Retraction Note: Deep learning approach to predict autism spectrum disorder: a systematic review and meta-analysis. BMC Psychiatry. 2025; 25(1): 1104.

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13. Dong B, Chang M, Liu J, Li K, Xiao H, Wu S, Feng D, Guo B. Changes in peripheral immune cell phenotypes and their roles in autism: insights from clinical and animal model studies. Mol Psychiatry. 2025.

Autism Spectrum Disorder (ASD), a group of highly heterogeneous and multifactorial neurodevelopmental disorders, is characterized by core clinical manifestations, including social deficits and repetitive stereotyped behaviors. Although its etiology involves both genetic and environmental factors, the exact pathogenesis remains elusive. Recent biological studies have untangled a pathological framework related to the « immune-neurodevelopmental axis », which has emerged as a potential paradigm for deciphering the complex mechanisms underlying ASD. In this framework, adaptive and innate immunity dysfunctions are thought to potentially contribute to disease progression. This review integrates evidence from clinical cohort studies and animal models to elucidate the functional phenotypic alterations of the three major peripheral immune cell subsets in ASD. Furthermore, it explores the multidimensional cascade of pathogenic mechanisms in which peripheral lymphocyte phenotypes may be involved, thereby providing collective evidence to support the future development of immune-modulatory therapeutic strategies for ASD.

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14. Dougnon G, Matsui H. Behavioral and molecular insights into anxiety in ube3a and fmr1 zebrafish models of autism spectrum disorders. Transl Psychiatry. 2025.

Angelman syndrome and Fragile X syndrome are neurodevelopmental disorders (NDDs) caused by mutations in the UBE3A and FMR1 genes, respectively. However, they share common features such as cognitive and motor deficits, anxiety, and impaired social behavior. In this study, we utilized zebrafish as an animal model to investigate the anxiety-like effects of mutations in these genes across larval and adult stages, employing two widely used behavioral assays: the light-dark test (LDT) and the novel tank diving test (NTT). We conducted detailed analyses of anxiety-like behaviors and exploration patterns in ube3a and fmr1 mutant fish, comparing both genotypes to their respective wild-type (WT) counterparts. Importantly, we analyzed RNA sequencing data from both larvae and adults to better understand the molecular pathways associated with the anxiety profiles of these genotypes. Our results show that larval ube3a mutants did not exhibit significant difference in the LDT compared to the WT; however, they showed significant reductions in distance travelled, velocity, and light-zone exploration during adult stages. In contrast, fmr1 mutants exhibited reduced locomotor activity in the LDT at larval age and hyperactivity and lower anxiety-like behaviors in adulthood. We identify key genes implicated in these behaviors and shared pathways that warrant further investigation for the development of therapies addressing ASD. Ultimately, our results highlight the importance of using different behavioral assays, such as the LDT and NTT, combined with omics approaches like RNA sequencing, to discern the distinct behavioral phenotypes caused by genetic mutations and to create opportunities for better understanding NDDs.

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15. Elshahary A, Safwan H, Abdelwaly A, Arafa RK, Helal MA. Discovery of indole- and quinolone-based inhibitors of the mTOR/Akt/Pi3K pathway for the potential treatment of autism and certain types of cancer. RSC Med Chem. 2025.

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that belongs to the PI3K-related protein kinase family. It is an integral part of two functionally distinct protein complexes: mTOR complex 1 and mTOR complex 2. Its signaling pathway is linked to cell survival, growth, proliferation, and motility. Deregulation of the mTOR pathway has been reported in many types of cancer. Hence, mTOR is an attractive target for the treatment of certain cancers such as renal cell carcinoma and pancreatic tumors. In addition, hyperactivity in mTOR-mediated signaling is associated with the pathogenesis of autism spectrum disorder (ASD) and Alzheimer’s disease. Recently, mTOR inhibitors have been considered as emerging pharmacotherapy for these disorders. In this research, we have used molecular modeling techniques to design three series of compounds, indoles, β-carbolines, and 4-aminoquinolines, targeting the ATP site of the mTOR kinase. Based on insights from molecular docking, we developed twenty eight derivatives of these scaffolds to explore the SAR and optimize their affinities. The prepared compounds were evaluated for their inhibitory activity against mTOR as well as other closely related kinases such as PI3K and AKt. To our delight, twenty compounds have shown sub-micromolar activities towards the mTOR kinase. Compounds HA-2l and HA-2c showed a superior IC(50) of 66 and 75 nM, respectively, for mTOR, while being selective against AKt and Pi3K. Upon optimization, these selective inhibitors could be useful for the management of ASD due to their relatively higher safety and, hence, suitability for long-term use. On the other hand, derivatives HA-1e, HA-2g, and HA-3d exhibited high affinities for the three enzymes, suggesting their potential utility as anticancer agents. Also, the cytotoxicity of the most active compounds was assessed using different cell-lines. Compounds HA-2g, HA-2l, and HA-3d showed sub-micromolar inhibition, in the range of 0.610-0.780 μM, against the tested cancer cell lines MDA-MB231 and HCT-116. The discovery of a clinically useful mTOR inhibitor would represent a new hope for patients of two important non-communicable diseases, cancer and ASD.

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16. Esen Öksüzoğlu M, Ünal D, Nalbant K, Kiliç B, Devecioğlu HB, Saruhan K, Ergül B, Çelik YS. Autistic traits in children with comorbid Specific Learning Disorder and Attention-Deficit/Hyperactivity Disorder: cognitive, behavioral, and teacher-reported predictors. J Clin Exp Neuropsychol. 2025: 1-12.

BACKGROUND: Children with comorbid Specific Learning Disorder (SLD) and Attention-Deficit/Hyperactivity Disorder (ADHD) often show elevated autistic traits, yet contributing cognitive and behavioral factors remain underexplored. This study compared cognitive-behavioral profiles of ADHD-only and SLD+ADHD groups and identified key autistic trait predictors using a multi-informant approach. METHODS: The study included 150 children aged 8-12 years, equally divided into ADHD-only and SLD+ADHD groups. Assessments included the Social Responsiveness Scale (SRS) for autistic traits, the Strengths and Difficulties Questionnaire (SDQ) for emotional-behavioral problems, a teacher-rated SLD Symptom Checklist (SLD-SC), and a clinician-administered cognitive battery (SLD-Battery of Cognitive Skills [SLD-BC]). RESULTS: Controlling for ADHD medication, children with SLD+ADHD had significantly higher SRS scores (p < .001), greater impairments on SLD-SC and SLD-BC, and higher SDQ-impact scores (p = .046). Stepwise regression identified SLD diagnosis, SLD-SC motivation and hyperactivity, SLD-BC head test and motor skills, and SDQ peer problems and hyperactivity as significant predictors of SRS scores, explaining 48.0% of the variance (R(2) = .480, F(7, 142) = 18.703, p < .001). CONCLUSION: Autistic traits in children with neurodevelopmental comorbidity are closely tied to motivational, executive, and sensorimotor deficits. Findings emphasize the need for integrated cognitive, behavioral, and teacher-reported evaluations to guide targeted interventions in complex developmental profiles.

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17. Fadl-Elmula I, Abdel-Raheem SY, Khalid R. Atypical case of Rett syndrome with concurrent MECP2 gene mutation and del(15)(q22qter) karyotype: A case report and review of literature. World J Clin Pediatr. 2025; 14(4): 109874.

BACKGROUND: Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000) girls due to de novo mutations in the methyl-CpG binding protein 2 (MECP2) gene mapped to chromosome Xq28. The disease-causing gene was identified as a mutation in the MECP2 gene, which is found in approximately 80% of patients diagnosed with Rett syndrome. Although chromosomal changes resulting in del(15)(q11q13) are usually associated with Angelman and Prader-Willi syndrome, very few cases, if any, of Rett syndrome with terminal 15q22-qter deletion have been published in English literature. CASE SUMMARY: In this study, we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl. The patient was brought in by her parents, complaining of gradual onset of abnormal walking, abnormal hand movement, loss of speech, and mental retardation for ten years. There was no reported history of convulsions or loss of consciousness. Clinical examination revealed microcephaly with no other apparent dysmorphic features, intact cranial nerves, and abnormal gait. She showed repetitive and stereotyped behaviors, including hand flapping, stimming, and chest pounding, which were concomitant with autism spectrum disorder. Magnetic resonance imaging and electroencephalography investigations were normal, and cytogenetic analysis showed 46,XX, del(15)(q22qter). Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine > thymine at nucleotide 401, leading to phenylalanine replacing a serine at amino acid position 134. CONCLUSION: This case, the first reported instance of Rett syndrome in Sudan, is of significant interest. The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion, which may explain the autistic behavior with atypical presentation of Rett syndrome. This report expands the genetic diversity of Rett syndrome, demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.

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18. Flynn C, Carr K, Whiteley P, Nirmalkar K, Bellinghiere A, Hahn J, Liu H, Arici H, Hewitson L, Devlin M, Pollard E, Pathak K, Garcia K, Rosales A, Pirrotte P, Kalb D, Keen R, Kenyon V, Fasano A, Krajmalnik-Brown R, Adams J. Elevated Microbially-Derived Metabolites in Autism: A Possible Diagnostic Screening Test for a Distinct ASD Phenotype. Res Sq. 2025.

Many studies have confirmed that a subset of children with autism spectrum disorder (ASD) have unusually high urinary concentrations of harmful microbially-derived metabolites (MDMs) such as p-cresol sulfate and indoxyl sulfate. We hypothesized that these MDMs may affect neurodevelopment through the gut-brain axis and that a sub-phenotype characterized by gut dysbiosis may be present in most ASD individuals. This multi-site study involved measuring the concentrations of many MDMs in the urine of 52 children with ASD and 47 healthy, typically developing (TD) children, aged 2 to 11 years. The measurements were conducted first with untargeted semiquantitative Liquid Chromatography and Mass Spectrometry (LC-MS), followed by targeted quantitative LC-MS. The ASD group had significantly higher concentrations of many MDMs compared to the TD group. The MDMs included phenylalanine-derived, tryptophan-derived, and yeast-derived MDMs. Almost all children with ASD had one or more MDMs at concentrations above any TD child, and sometimes 100-1000x higher. The children with ASD had an average of 3 MDMs at levels above any TD child, compared to zero (by definition) for the TD children. Classification using one or more elevated MDM yielded a sensitivity of 90% and a specificity of 100%. This MDM System™ is a promising non-invasive method for diagnostic screening for ASD in children ages 2 to 11 years. These data also suggest approximately 90% of children with ASD have a distinct phenotype of ASD, which we propose naming ASD associated with Microbially-Derived Metabolites (ASD-MDM), defined by quantitative laboratory measurements of these metabolites in urine.

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19. Gonzalez-Herrero B, Coebergh J, Pagonabarraga J, Morgante F, Deeley Q, Edwards MJ. Structured clinical diagnostic assessment reveals autism spectrum disorder in adults with functional neurological disorder. Sci Rep. 2025; 15(1): 40423.

Emerging evidence suggests a link between Autism Spectrum Disorder (ASD) and Functional Neurological Disorder (FND), underscoring the importance of considering neurodevelopmental traits in neurological care. This study examined the prevalence of clinically probable ASD (CP-ASD) in a specialist FND clinic and explored its associations with symptom presentation, mental health, alexithymia and interoceptive awareness. Sixteen consecutively recruited adults with FND underwent comprehensive ASD assessment, including self-report questionnaires (RAADS-R, AdAS Spectrum), observational interview (ADOS-IV), and evaluation against DSM-5 criteria. Additional validated psychometric measures assessed anxiety (GAD-7), depression (PHQ-9), dissociation (Cambridge Depersonalization Scale, CDS), alexithymia (TAS-20), camouflaging (CAT-Q), and interoceptive sensibility (MAIA-2). Half of the participants (n = 8) met criteria for CP-ASD. Compared with the non-CP-ASD group, the CP-ASD group had a younger age at symptom onset and a longer interval from onset to FND diagnosis. After correction for multiple comparisons, significant group differences remained for anxiety (GAD-7), dissociation (CDS), and camouflaging behaviours (CAT-Q total, Compensation, and Assimilation subscales). Several further differences reached uncorrected significance with large effect sizes, including alexithymia (TAS-20) and the MAIA-2 Not Worrying and Emotional Awareness subscales, but did not survive correction and should be considered exploratory. Among functional symptom types, only sensory symptoms differed, being more prevalent in the CP-ASD group (62.5% vs 12.5%, p =.021), while treatment response did not differ between groups. . These findings suggest that ASD may frequently co-exist with FND but remain under-recognised. Incorporating routine screening and neurodevelopmentally informed care could improve diagnostic accuracy and support more personalised interventions. Larger, adequately powered studies are needed to confirm these preliminary results and to clarify further the role of neurodevelopmental factors in the onset, persistence, and treatment response of FND.

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20. Hasan H, Hagerman R, Say DS, Nguyen AP, Babata K, Oyegbile-Chidi T, Herrera-Guerra A, Torrents C, Silver CE, Restrepo B. Parallel paths: A narrative review exploring autism and its co-occurring conditions. World J Clin Pediatr. 2025; 14(4): 111641.

Autism is a heterogeneous condition with a rising prevalence and demand for specialized care. Autistic children are more likely than neurotypical peers to experience co-occurring conditions (CCs), including medical, psychiatric, and behavioral issues, highlighting the urgent need for autism-competent healthcare providers in general healthcare. This review aims to equip primary care providers (PCPs) with a concise summary of common CCs and strategies for effective identification. A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature, research evidence, and existing clinical trial outcomes, supplementing their clinical expertise. Autistic children consistently show higher rates of both medical and mental health issues. Despite greater healthcare utilization, many autistic individuals report unmet needs. CCs can impair behavior, functioning, and well-being, but are often treatable when recognized early. Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families. This evidence-based review supports PCPs in enhancing their knowledge, fostering early recognition, and delivering comprehensive, responsive care.

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21. Jiang S. Bridging the gap: explainable ai for autism diagnosis and parental support with TabPFNMix and SHAP. Sci Rep. 2025; 15(1): 40850.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition that affects a growing number of individuals worldwide. Despite extensive research, the underlying causes of ASD remain largely unknown, with genetic predisposition, parental history, and environmental influences identified as potential risk factors. Diagnosing ASD remains challenging due to its highly variable presentation and overlap with other neurodevelopmental disorders. Early and accurate diagnosis is crucial for timely intervention, which can significantly improve developmental outcomes and parental support. This work presents a novel artificial intelligence (AI) and explainable AI (XAI)-based framework to enhance ASD diagnosis and provide interpretable insights for medical professionals and caregivers. The proposed framework leverages advanced classification models, specifically the TabPFNMix regressor, which is optimized for structured medical datasets. Unlike traditional machine learning methods, TabPFNMix demonstrates superior performance in capturing complex ASD-related patterns. To address the black-box nature of AI models, Shapley Additive Explanations (SHAP) is integrated to provide transparent and interpretable reasoning behind the model’s decisions, ensuring better understanding for clinicians and caregivers. Extensive experiments were conducted using a publicly available benchmark dataset, with performance evaluated through standard metrics such as accuracy, precision, recall, F1-score, and AUC-ROC. Comparative analysis with baseline models, including Random Forest, XGBoost, Support Vector Machine (SVM), and Deep Neural Networks (DNNs), demonstrates that TabPFNMix achieves the highest accuracy (91.5%), surpassing XGBoost (87.3%) by 4.2 percentage points. Additionally, it attains superior recall (92.7%), precision (90.2%), F1-score (91.4%), and AUC-ROC (94.3%), ensuring both high diagnostic accuracy and robustness in real-world ASD screening. An ablation study highlights the significance of feature selection and preprocessing, revealing that omitting key features or preprocessing steps (such as normalization and missing data imputation) significantly degrades performance. Furthermore, SHAP-based feature importance analysis identifies social responsiveness scores, repetitive behavior scales, and parental age at birth as the most influential factors in ASD diagnosis. These insights align with medical literature, reinforcing the reliability of the model’s predictions and its applicability in clinical settings.

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22. Kawamura N, Sakamoto M, Hashimoto C, Ozeki Y, Machida K. Parental perceptions of the psychosocial outcomes of equine-assisted activities and therapies for children with autism spectrum disorder in Japan: a phenomenological study. Int J Qual Stud Health Well-being. 2025; 20(1): 2585638.

BACKGROUND: Children with autism spectrum disorder (ASD) often experience challenges in social communication, behavioral regulation, and daily life adaptation. Equine-assisted activities and therapies (EAATs) have been implemented as complementary approaches to support psychosocial development. However, little is known about the experiences of parents in Japan whose children participate in EAATs. AIM: The study aims to qualitatively explore how parents in Japan perceive the psychosocial outcomes of EAATs for their children with ASD. By focusing on parental perspectives, this study seeks to clarify how EAATs may contribute to the well-being of both children and their families, and to inform the development of supportive therapeutic environments. METHODS: This qualitative study employed a phenomenological approach. Semi-structured interviews were conducted with ten parents whose children with ASD had participated in EAATs for a minimum of six months. Thematic analysis was guided by Colaizzi’s method. RESULTS: Four primary developmental stages emerged from the analysis of children’s experiences: (1) Learning physical and mental harmony, (2) Exploring interests and strengthening bonds with oneself and others, (3) Inspiring independence and interaction, and (4) Building resilience and communication skills. Furthermore, parents reported three overarching outcomes from their own involvement: (1) Parental well-being and engagement through horseback riding, (2) Parental joy and recognition of their child’s growth, and (3) Fostering Family Connection and parent-to-parent interaction. Participant narratives illustrated these themes vividly, highlighting specific examples of behavioral and emotional change. CONCLUSIONS: EAATs were perceived by parents as fostering not only the psychosocial growth of children with ASD but also enhancing parental well-being and family cohesion. To support children’s psychosocial development and promote the health and well-being of their parents, nurses could play a distinctive role by observing both psychological and physical changes, monitoring how these influence daily functioning and interpersonal relationships, and supporting parents in interpreting their child’s developmental progress.

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23. Krawczyk M, Pinkham A, Okruszek Ł. Similar or opposite? Differences in the recognition of communicative intentions from biological motion in adults with autism and schizophrenia. J Psychiatr Res. 2025; 193: 32-40.

Potential similarities between autism and schizophrenia have been studied for decades, with overlap within various social cognitive (SC) domains including mentalizing and emotion recognition difficulties. However, no direct comparison of low-level communicative intention recognition is available to date. To address this gap, we compared individuals with autism (ASD; N = 29), schizophrenia (SCZ; N = 58) and a non-clinical control group (NCC; N = 29) on their ability to recognize communicative intentions from biological motion (BM). Participants completed two BM tasks assessing communicative cues recognition with either single or dyadic point-light displays (PLDs) and one BM emotion recognition task. Additionally, two batteries of neurocognitive and SC functioning were administered. Both clinical groups scored lower than NCC in the dyadic task, with the SCZ group also performing lower than the ASD group (SCZ < ASD < NCC). Although accuracy in the categorization of single-agent actions was only decreased in SCZ participants (SCZ < ASD, NCC), accuracy of freely-generated descriptions in this task was lower in both clinical groups compared to NCC, with no significant difference between ASD and SCZ (ASD, SCZ < NCC). Finally, only the SCZ group scored lower than NCC in emotion recognition from BM. The SCZ group also scored lower than the ASD group on the majority of neurocognitive and SC measures. The obtained results confirm that both schizophrenia and autism might be associated with difficulties in low-level intention recognition based on BM stimuli, although these deficits were generally more prominent in the SCZ group, with exception of a Gestures subtask that required freely-generated verbal responses. Obtained results suggest the existence of potentially diverging mechanisms of SC alterations in autism and schizophrenia. Thus, including sensitive, BM-based measures of communicative intention recognition into research practice may help to address this issue.

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24. Luo J, Shao W, Wu Y, Huang H, Xu G, Qi Y, Overton P, Zheng Y, He F. A Network Analysis of ADHD and ASD Symptoms in Chinese Children: Insights on Age and Gender Differences. Int J Methods Psychiatr Res. 2025; 34(4): e70042.

OBJECTIVE: This study aimed to explore the transdiagnostic interactions between ADHD and ASD symptoms in Chinese children, identifying core and bridging symptoms, and examining differences in symptom networks across gender and age subgroups. METHOD: Using data from a nationwide mental health survey of 71,217 Chinese children (mean age = 11.49, SD = 2.82), a symptom network analysis was conducted. ADHD and ASD symptoms were assessed via the Child Behavior Checklist (CBCL), with ASD items selected from an empirically derived CBCL autism scale. Network estimation was performed using the Glasso algorithm, and community detection was achieved through exploratory graph analysis (EGA). Network comparison tests (NCT) were used to evaluate differences in network structure and connectivity between gender (male vs. female) and age (younger vs. older) subgroups. RESULTS: Inattentive symptoms (I8 « Cannot concentrate, » I78 « Inattentive/easily distracted ») emerged as central bridging nodes linking ADHD and ASD symptoms. Three stable communities were identified: (1) an inattentive/internalizing cluster reflecting overlapping ADHD-inattentive and ASD features, (2) a hyperactive/impulsive and immature behavior cluster, and (3) a social withdrawal/low energy cluster representing core ASD features. Females exhibited significantly higher network connectivity than males (global strength: S = 1.05, p = 0.03), with tighter symptom interplay. Older children showed greater ADHD-ASD symptom overlap, though global strength differences were non-significant (S = 0.70, p = 0.13). CONCLUSION: Two inattentive symptoms (I8 and I78) emerged as among the most strongly connected items in the combined ADHD-ASD symptom profile, suggesting that attentional difficulties could play an important role in the psychopathological mechanisms underlying both conditions. Nevertheless, this cross-sectional finding does not establish causality; longitudinal and intervention studies remain necessary. Screening approaches tailored to gender differences and local cultural context could improve identification of these symptoms in Chinese children and adolescents. The present findings may also guide future refinements in school mental-health support and related policy development.

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25. Mohammadi F, Shahrokhi H, Asadzadeh A, Pirmoradi S, Moghtader A, Rezaei-Hachesu P. Artificial Intelligence in Autism Spectrum Disorder Diagnosis: A Scoping Review of Face, Voice, and Text Analysis Methods. Health Sci Rep. 2025; 8(11): e71476.

BACKGROUND: Autism is a complex neurodevelopmental condition affecting social interaction and behavior. Traditional diagnostic methods, relying on observational techniques and interviews conducted by trained professionals, remain the gold standard for ASD diagnosis. However, these methods can be time-consuming and may be influenced by subjective factors. Recent advancements in artificial intelligence (AI) offer promising approaches to augment existing methods, potentially enhancing efficiency and providing additional objective data through facial, vocal, and textual analysis. OBJECTIVE: The objective of this study was to conduct a comprehensive review of artificial intelligence applications in autism spectrum disorder (ASD) diagnosis, specifically focusing on facial, vocal, and textual analysis methods. METHODS: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and Google Scholar. The findings were reported in accordance with the PRISMA checklist. Data were collated and summarized, and results were reported qualitatively, adopting a narrative synthesis approach. RESULTS: In facial image analysis, deep learning algorithms demonstrated high accuracy in identifying autism-related facial features, algorithms such as Xception achieved 98% accuracy, while hybrid approaches like the combination of Random Forest (RF) and VGG16-MobileNet showed accuracy at 99%. Voice analysis studies utilized both traditional machine learning methods and advanced deep learning techniques, achieving accuracies between 70% and 98% in detecting atypical speech patterns and prosodic abnormalities associated with autism. Text-based analyses showed potential in identifying linguistic markers of autism through natural language processing techniques. Overall, Deep learning approaches were mainly employed in facial image analysis for autism diagnosis. In contrast, voice and text recognition studies utilized machine learning algorithms. CONCLUSIONS: This review demonstrates artificial intelligence’s significant role in diagnosing autism spectrum disorder (ASD). These AI-driven approaches can complement traditional diagnostic methods, potentially leading to earlier interventions and improved outcomes for individuals with ASD.

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26. Ni SY, Lu CC, Wu CT, Hsieh MH, Chen IM, Lin C, Lai FP, Chien YL. An exploratory study on predicting depressive symptoms in autistic individuals using wearable devices and machine learning. J Formos Med Assoc. 2025.

BACKGROUND: Monitoring depressive symptoms in autistic individuals is challenging due to conditions in communication and emotional expression inherent to this population. For early detection of depressive symptoms in autistic adults, this study aims to leverage digital biomarkers from wearable devices and develop monitoring models using machine learning algorithms. METHODS: This prospective, observational study recruited 17 autistic adults (mean age 29.1 ± 8.2 years). Physiological biomarkers, including activity level, heart rate, and sleep duration, were continuously collected via smartwatches. Depressive symptoms were self-rated weekly using the Beck Depression Inventory (BDI). Machine learning models, including Extreme Gradient Boosting (XGBoost), were applied to analyze the longitudinal data. The models were assessed using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy, precision, and F1 score. Feature importance analysis was conducted to identify key digital biomarkers. RESULTS: The XGBoost model demonstrated superior predictive efficacy, identifying depressive states with an 84 % accuracy and an area under the receiver operating curve (AUROC) of 0.91. Lower activity levels, decreased sleep duration, and reduced average heart rate emerged as potential predictors for depressive states. CONCLUSION: Digital phenotypes derived from wearable devices may facilitate the detection of depressive symptoms in autistic adults, offering potential benefits for clinical assessments and emotion self-care.

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27. Oulton K, Wray J, Foo-Caballero M, Flynn S, Harniess P, Rao A, Gibson F. The seen and be heard study: A national mixed methods study to identify the barriers and facilitators to ensuring equitable cancer care for children with and without learning disabilities and/or who are autistic – Protocol Paper. PLoS One. 2025; 20(11): e0333020.

INTRODUCTION: A strong body of evidence exists relating to inequality in general healthcare experience and outcomes for children and young people with learning disabilities and/or who are autistic compared to those without. Healthcare practitioners describe feeling less capable and confident to deliver care to children with learning disabilities, as well as having less capacity. However, there is little research specifically in cancer care that explores access and acceptability of provision for children with learning disabilities and/or those who are autistic. This is despite some cancers being more prevalent in syndromes associated with learning disabilities, for example Down’s Syndrome. We aim to explore the needs and experiences of children with/without learning disabilities and/or who are autistic and their families receiving cancer care. This inclusive study will provide evidence of whether, and what, inequity exists, for whom and why, generating evidence of what issues affect all children and young people receiving cancer care and what are particular to those with learning disabilities and/or who are autistic. METHODS AND ANALYSIS: We will use a transformative mixed methods design, comprising an individual staff and organisational level survey, retrospective case note review, ethnographic observations of clinical care, family and staff interviews, and participatory workshops. The ethnographer will follow and observe individual children and their families. We will use a ‘toolbox’ of creative participatory methods, including providing a co-designed research data collection journal to support elicitation of the child’s perspective. Data will be analysed using thematic analysis. The study will run from January 2025 to January 2026. The project is registered on ClinicalTrials.gov (Identifier: NCT06481527). Health Research Authority approval has been granted (REC Reference no. 24/LO/0410 | IRAS Project ID: 335623). DISCUSSION: The mixed methods approach using survey and qualitative design will support a broad scope and in-depth understanding of the barriers and facilitators to inform equitable cancer care delivery for children with and without learning disabilities and/or who are autistic. Potential limitations are acknowledged. For example, resource constraints mean that the focus of the ethnography work package is within two hospital sites, which may limit broader comparisons and thematic development. Dissemination of findings will include papers specific to each work package. Recommendations for clinical practice will be developed, including staff training, healthcare planning and innovative solutions for improving the cancer care experience. These outputs will directly inform quality improvement from a local to national and international context in cancer care around children and young people with learning disabilities and/or who are autistic.

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28. Renteria RA, Grineski SE, Gomez J, Bilder D, Collins TW, Bakian AV. Associations between prenatal PM(2.5) exposures and intellectual disability: Are there differential impacts based on co-occurrence of autism spectrum disorder?. Environ Res. 2025: 123378.

Prenatal fine particulate matter (PM(2.5)) has been associated with intellectual disability (ID) and autism spectrum disorder (ASD), separately. Its role in co-occurring ID with ASD (ID+ASD) is less understood. To address this gap, this study uniquely disaggregates ID-only from ID+ASD to assess the associations between prenatal PM(2.5) exposure and odds of ID-only and ID+ASD across multiple exposure windows and measures. For children born in Utah, U.S.A., children with ID (ID-only and ID+ASD) were matched 1:3 with non-ID affected controls. PM(2.5) exposure was estimated across four prenatal periods (i.e., preconception, 1(st), 2(nd), and 3(rd) trimester) using long-term averages and exceedances of WHO and U.S. NAAQS 24-hour thresholds and assigned to children. Associations were examined using multilevel multinomial logistic regressions. Results show that increase in long-term PM(2.5) during preconception and first trimester was associated with increased odds of ID-only and ID+ASD. Exceedances of the WHO 24-hour threshold (15 μg/m(3)) during preconception were linked to ID-only, while first trimester WHO 24-hour exceedances were linked to both ID-only and ID+ASD. U.S. NAAQS 24-hour threshold (35 μg/m(3)) exceedances during preconception and first trimester were associated with ID+ASD. Results reveal that long-term PM(2.5) exposure during preconception and the first trimester elevates risk for both ID-only and ID+ASD. ID+ASD appears particularly sensitive to preconception and first trimester exceedances of the U.S. NAAQS 24-hour threshold, whereas ID-only may be more sensitive to exceedances of the WHO 24-hour threshold during preconception. By distinguishing these neurodevelopmental outcomes, these results underscore timing and magnitude of prenatal PM(2.5) exposure differentially influence neurodevelopmental risk. They also highlight the need for targeted public health interventions and stronger air quality regulations to protect early neurodevelopment.

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29. Sharma M, Pamidi SC, Divi PK, Mohapatra S, George B, Sneha KP, Kreutzmann JC, Annamneedi A. Genetic crosstalk of autism spectrum disorders and epilepsy: an insight into the presynapse. Front Neurol. 2025; 16: 1677134.

The neurodevelopmental disorder autism spectrum disorder (ASD) affects 0.5%-1% of the global population and is marked by ongoing difficulties in social communication and cognitive function. Interestingly, ASD has been reported to share a genetic origin with epilepsy, a condition marked by recurrent, unprovoked seizures. Both ASD and epilepsy are caused by multifactorial and multigenetic origin. Whereas the number of genes linked to ASD etiology are growing, the genetic basis of epilepsy is more diverging leading to distinct epileptic syndromes. Despite decades of discussion, a comprehensive understanding of the genetic interplay between these disorders remains elusive. Our article focuses on investigating the shared genetic basis of abnormalities in synaptic proteins, highlighting the presynaptic compartment, which is less explored compared to the postsynaptic elements. We identify those biological processes linked to the presynaptic compartment, such as presynaptic assembly, ATP metabolism, various aspects of the synaptic vesicle cycle, are commonly affected across conditions, as evidenced by the shared genetics. Hence, this study offers initial insights into presynaptic signaling, and further research could aid in developing improved therapeutic strategies by targeting these presynaptic processes.

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30. Simon AJ, Picard N, d’Andrea V, Chang E, Leffler J, Centofante E, Taylor M, Bardi F, Cavicchiolo F, Hensch TK, Panzeri S, Chen C, Fagiolini M. Visual Recovery Reflects Cortical MeCP2 Sensitivity in Rett Syndrome. Ann Clin Transl Neurol. 2025.

OBJECTIVE: Rett syndrome (RTT) is a devastating neurodevelopmental disorder with developmental regression affecting motor, sensory, and cognitive functions. Sensory disruptions contribute to the complex behavioral and cognitive difficulties and represent an important target for therapeutic interventions. Although genetic medicine-based therapies targeting MeCP2 have successfully restored motor and respiratory functions in animal models, their ability to reverse sensory deficits across levels of the visual pathway remains largely unexplored. METHODS: Using genetically reversible mouse models of MeCP2 deficiency (Mecp2(stop/y) and Mecp2(stop/x)), we applied advanced electrophysiological, anatomical, and behavioral techniques to evaluate visual function, a critical sensory domain impaired in both animal models and RTT patients. RESULTS: In Mecp2(stop/y) mice, initiating MeCP2 expression after postnatal day 35 (P35) reversed progressive cortical dysfunction, prevented thalamic circuit disorganization, and restored visual function, despite some remaining cortical anatomical abnormalities. Even in fully regressed adult Mecp2(stop/x) heterozygous female mice, MeCP2 reactivation was sufficient to reduce the symptoms. INTERPRETATION: These findings highlight the remarkable sensitivity of cortical circuits to MeCP2 expression in both developing and mature brain. Importantly, restoring just 60%-70% of MeCP2 protein levels was sufficient to rescue sensory functions, even after the onset of regression. This underscores the transformative potential of genetic medicine-based therapies in RTT, suggesting that even partial restoration of MeCP2 can meaningfully improve sensory processing and quality of life for patients.

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31. Soto-Icaza P, Oyarzun M, Yaikin T, Arcos-Polanco M, Candia C, Rodríguez-Sickert C, Billeke P. Autism shapes social integration and reciprocity in elementary classrooms. Sci Rep. 2025; 15(1): 40473.

During childhood, schools are crucial environments for social interactions, making them ideal for evaluating the inclusion of students with special educational needs (SEN). In particular, autistic children often face challenges in peer relationships, yet the impact of autism on social dynamics in schools is not well understood. To address this issue, we examined social dynamics within elementary schools. We hypothesized that, compared to their non-autistic peers, autistic children occupy more peripheral positions in social networks and engage less in reciprocal relationships. To test these hypotheses, we introduced a novel ecological approach using experimental game theory to quantify social integration and reciprocity among autistic children. Social networks were constructed for each classroom based on the children’s peer selections during a distributive game where they had to send tokens to their peers. Six elementary schools took part in this study. From these schools, 26 classrooms from first to fourth grade were included, comprising a total of 625 students aged 6 to 11. Among them, 464 were students without SEN, 143 were students with SEN excluding autism, and 18 were autistic students. Our analysis showed that autistic children and children with SEN were significantly less central and less involved in reciprocal peer relationships compared to children without SEN. Due to the small sample of autistic students, further research with greater statistical power is needed to clarify the specificity of the results. These findings highlight the need for support in promoting social inclusion while also emphasizing the importance of exploring the intersection of neurodevelopmental conditions and social dynamics.

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32. Su J, Gupta R, van Hoof S, Kreye J, Prüß H, Spielman B, Brimberg L, Volpe BT, Huerta PT, Diamond B. Heterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity. Transl Psychiatry. 2025; 15(1): 498.

Maternal anti-Caspr2 (Contactin-associated protein-like 2) antibodies have been associated with increased risk for autism spectrum disorder (ASD). Previous studies have shown that in utero exposure to anti-Caspr2 antibodies results in a phenotype with ASD-like features in male mice. Here we ask whether four newly generated antibodies against Caspr2 are pathogenic to the developing fetal brain and whether they function through similar means. Our results show that these novel anti-Caspr2 antibodies recognize different epitopes of Caspr2. In utero exposure to these antibodies elicits differential behavioral phenotypes in male offspring, as demonstrated in the social interaction task, as well as phenotypic alterations in the open-field and light-dark tasks. These results demonstrate variability in the antigenic specificity and pathogenicity of anti-Caspr2 antibodies which may have clinical implications.

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33. Suspitsin EN, Malysheva KS, Laptiev SA, Sharonova OS, Abuzova AS, Kuznitsyna AA, Melashenko TV, Efremova OV, Korzun PR, Binnatova JO, Gorgul YA, Syomina MV, Imyanitov EN. Monogenic defects in Russian children with autism spectrum disorders. World J Clin Pediatr. 2025; 14(4): 108733.

BACKGROUND: Autism spectrum disorders (ASD) represent a substantial social problem affecting at least 1 in 100 children worldwide. These conditions are very often accompanied by intellectual disability (ID) and speech delay; thus, they can be considered within a clinical continuum of neurodevelopmental disorders. Given the high heterogeneity of ASD, the subjective nature of diagnostic criteria, and the presence of phenocopies, identifying genetic determinants of these disorders remains a challenge. AIM: To investigate the spectrum and frequency of rare genetic variants in genes with proven association with ASD in Russian children. METHODS: 110 patients from 106 families were recruited into the study (mean age at diagnosis 6 years; boy-to-girl ratio 3:1. Most of the patients (84%) demonstrated a combination of ASD with developmental delay (DD) or ID. Patients with syndromic features were subjected to the chromosomal microarray analysis. The remained children underwent clinical exome sequencing aimed at identifying presumably monogenic causes of ASD. The study focused on rare (minor allele frequency ≤ 0.001) variants affecting high-confidence ASD-associated genes. RESULTS: Pathogenic copy number variations were detected in three (7%) of the patients examined. Clinical exome sequencing revealed pathogenic/likely pathogenic variants in 12 of 105 cases (11%), indicating the presence of monogenic syndromes with established clinical significance (Pitt-Hopkins syndrome, ZTTK syndrome, syndromic X-linked ID of Billuart type, Snijders-Blok-Campeau, Helsmoortel-van der Aa, Coffin-Siris, Clark-Baraitser, Keefstra syndromes, etc.). In addition, 27 patients (26%) had 37 rare variants of unknown clinical significance in DSCAM, SHANK2, AUTS2, ADNP, ANKRD11, APBA2, ARID1B, ASTN2, ATRX, SCN1A, CHD2, DEAF1, EHMT1, GRIN2B, NBEA, NR4A2, TRIO, TRIP12, POGZ, EP300, FOXP1, PCDH19, GRIN2A, NCKAP1, and CHD8 genes. No specific variant was detected more than once in unrelated patients. Among the genes with rare variants found in 2 or more patients were TRIP12 (n = 4), AUTS2 (n = 3), ARID1B (n = 3), PCDH19 (n = 3), EP300 (n = 3), TRIO (n = 2), ASTN2 (n = 2), EHMT1 (n = 2), and CHD2 (n = 2). Of note, 5 male ASD/DD patients from 3 unrelated families had PCDH19 missense variants, confirming that at least some hemizygous males with non-mosaic PCDH19 variants may present with neurobehavioral abnormalities. These variants did not cause epilepsy restricted to females in patients’ mothers or sisters. CONCLUSION: These data confirm a tremendous diversity of genetic causes of ASD. Clinical exome sequencing may serve as a reasonable alternative to whole-exome sequencing.

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34. Vyshedskiy A, Marsiglio A, Batham S, Tagliavia A, Venkatesh R, Tarakbay A, Mundhia S, Urs S, Khokhlovich E, Pinsky E. Age-Dependent Process Governs Executive Function Disability in Autistic Children. J Autism Dev Disord. 2025.

PURPOSE: Comprehension of syntactic language is facilitated by the executive function of Prefrontal Synthesis (PFS), defined as an ability to deliberately modify and juxtapose mental visuospatial objects. Autistic individuals often experience deficits in PFS. This study aimed to differentiate between two hypotheses regarding PFS acquisition. The first suggests a persistent, age-independent barrier that continuously hinders PFS development. The second proposes an age-dependent factor, such as a critical period for PFS acquisition. These hypotheses predict distinct learning trajectories: the first expects autistic individuals to exhibit a consistently slower PFS-learning rate across all ages, while the second predicts an initial learning rate comparable to neurotypical peers, followed by an early decline. METHODS: To test these predictions, we analyzed PFS development in 15,183 autistic and 138 neurotypical individuals aged 2 to 22 years using parent-reports. RESULTS: At age 2, both groups exhibited similar PFS-learning rates. In neurotypical individuals, this rate remained high until age 7. However, in autistic individuals, learning rates began to decline exponentially as early as 2.3 years, with an even earlier onset in those with severe autism. CONCLUSION: These findings support the second hypothesis, suggesting that PFS deficits in autism may stem from an age-dependent factor, such as a shortened critical period.

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35. Wang B, Xiao Y, Qian Y, Li S, Zhang H, Reiling K, Rozelle S. Effect of the ‘digital plus’ approach to upscaling early childhood development services in rural China: study protocol for a cluster randomised controlled trial. BMJ Open. 2025; 15(11): e099427.

INTRODUCTION: The high prevalence of developmental delays among young children poses significant barriers to long-term social mobility in low-income and middle-income countries. Digital interventions aimed at early childhood development (ECD) have shown promise in improving developmental outcomes, yet scalable and effective strategies remain under-explored. This study aims to evaluate the effectiveness of a digitally delivered parenting intervention to improve early child development in rural China. METHOD AND ANALYSIS: We design a parallel cluster-randomised controlled trial to evaluate a 12-month digitally delivered ECD intervention in rural China. Key inclusion criteria are households with children aged 6-24 months and without relocation intentions. Key exclusion criteria are children with a severe disability. Participants are masked to treatment assignment. The project implements village-level interventions in three counties in central China, involving 70 villages (clusters). Implementation involves two phases: the preparatory phase and the online phase, in which ‘Parenting the Future’ curriculum will be delivered through a newly developed mobile application. During the preparatory phase, county-level parenting trainers will conduct weekly home visits to each sampled household. In the online phase, caregivers will primarily access weekly parenting training through prerecorded videos on a mobile application. Trainers will conduct short, fortnightly home visits to manage toys and picture books loaned through the same application in accordance with the training. The planned total treatment involves 48 sessions over 1 year. Assessments were conducted via home visits at baseline and endline. The primary outcomes include cognitive development measured with the Bayley Scales of Infant and Toddler Development, third edition and social-emotional development measured with the age and stage questionnaire: social emotional. Secondary outcomes include caregiver engagement and the home learning environment measured by family care indicators and responsive caregiving rating scale. The trial aims to test the effectiveness and scalability of a hybrid ECD intervention. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the Institutional Review Board of Southwestern University of Finance and Economics. Informed consent will be obtained from all participants, with appropriate measures in place to ensure participant confidentiality. Results from the study will be shared through academic publications, policy briefs and presentations to government stakeholders and international organisations, contributing to policy discussions on the scalability of digital ECD interventions. TRIAL REGISTRATION NUMBER: AEA RCT Registry (AEARCTR-0013908); ISRCTN Registry (ISRCTN15854033).

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36. Wang L, Zheng L, Bai Y, Dill SE, Rozelle S. Parenting quality and early childhood development: evidence from different rural subpopulations in China. BMC Psychol. 2025; 13(1): 1273.

BACKGROUND: The quality of parenting can affect the developmental outcomes of young children. This study aims to investigate the associations between parenting quality and the early childhood development of children under age 3 across four major rural subpopulations in China. METHODS: Using a stratified cluster sampling method, 760 children aged 6-36 months and their primary caregivers in four rural subpopulations from four provinces and a metropolis in China were surveyed. Child development was assessed by the Third Edition of the Bayley Scales of Infant and Toddler Development. Parenting quality was measured using the Family Care Indicators. Data were analyzed using descriptive statistics, t-tests, multivariable regression analysis, and linear regression analysis. RESULTS: Across the four subpopulations, prevalences of delays of the sample children in four domains – cognition, language, social-emotional, and motor development are 52%, 45%, 52%, and 19%, respectively. The proportion of children with any type of delay is 82%, while over half (53%) have delays in at least two areas, and 27% have delays in three or more areas. Child’s mother as the primary caregiver, maternal education levels, and family asset values are all positively associated with the quality of parenting. Notably, low levels of parenting quality in rural China are linked to high rates of developmental delays. CONCLUSIONS: This study demonstrates that the level of parenting quality is significantly associated with early childhood developmental outcomes. Results highlight the need for raising investments in family care to improve early childhood development in different rural subpopulations in China.

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37. Wang X, Liu H, Zhu Y, Zhang H. Diagnosing autism in children using nonlinear dynamics of EEG signals and fuzzy extreme learning machines with feature optimization. Comput Methods Biomech Biomed Engin. 2025: 1-14.

Autism is a complex psychiatric condition that needs to be diagnosed early using more objective techniques. Hence, many researchers have turned to diagnosing autism by analyzing EEG signals. However, a comprehensive framework for this has not yet been introduced, and there is room for improvement. In this study, to increase the precision of autism diagnosis from EEG signals, a new framework is introduced that includes the steps of data preprocessing, extraction of nonlinear features from EEG time series, optimization of extracted features using an innovative technique based on GA and DBSCAN algorithms, feature reduction using the LASSO technique, and classification using a fuzzy ELM classifier. This study presents a feature optimization technique that leverages a genetic algorithm informed by clustering principles. Rather than relying on random selection for forming the new generation, the approach incorporates clustering during the fitness evaluation phase to identify and exclude outliers from advancing to the next generation. The recommended scheme was examined on two EEG databases. Using only 14-channel EEG data, it was able to achieve 96.81% accuracy, 95.16% sensitivity, 97.73% specificity, and a 96.42% F1-score for autism detection using database A, as well as 97.64% accuracy, 96.55% sensitivity, 98.49% specificity, and a 97.51% F1-score using database B. This framework outperformed existing methods on two EEG databases. The practical use of low-channel systems suggests potential for real-world clinical deployment, enabling scalable and cost-effective screening. This study underscores the potential of using nonlinear dynamics of EEG signals alongside fuzzy ELM for diagnosing autism in children.

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38. White LCJ, Schweizer K, Thomas KS. Disordered eating in autistic trans and gender diverse people: a lived experience-led scoping review. J Eat Disord. 2025; 13(1): 266.

BACKGROUND: This lived experience-led scoping review explores the evidence base related to eating disorders/disordered eating behaviours in Autistic trans and gender diverse (TGD) people. This review highlights the currently available data on eating disorder prevalence rates, comparisons with allistic and cisgender groups, drivers and maintenance factors, the relationship between eating disorders and gender-affirming medical care, and treatment outcomes in this population. METHODS: We conducted a search of the databases ProQuest, Medline, CINAHL, Cochrane Library, Web of Science, Scopus, and PsycINFO for articles relating to eating disorders/disordered eating behaviours in Autistic TGD people. Five articles published between 2021 and 2025 met the criteria for the review. RESULTS: The included articles were predominantly cross-sectional studies (n = 4) and one case series (n = 1). Researchers used a mixture of self-reported and clinically recorded eating disorder diagnoses, as well as validated measures, including the Eating Disorder Examination Questionnaire and the Nine-Item Avoidant/Restrictive Food Intake Disorder Scale. The literature highlights that the prevalence of eating disorders/disordered eating behaviours is high in the Autistic TGD population, and suggests that atypical presentations may be particularly common. Possible drivers and maintenance factors include sensory hypersensitivity, co-occurring Attention-Deficit Hyperactivity Disorder, gender dysphoria and passing concerns, and appearance pressures idealising thinness. Limited data were available on the role of gender-affirming medical care or eating disorder treatments, or on treatment outcomes. DISCUSSION: Further research is needed to better understand the nuances of eating disorders/disordered eating behaviours in Autistic TGD people. Key to future research inquiries should be the adoption of an intersectional approach, co-production of research with Autistic TGD people, and research considering treatment outcomes. We reviewed existing literature on eating disorders/disordered eating behaviours (EDs/DEBs) in Autistic trans and gender diverse (TGD) people. Five studies met our criteria. All were high-quality pieces published in the last five years. We found that Autistic TGD people have particularly high rates of EDs/DEBs and that atypical presentations may be more common. Autistic TGD people are exposed to the same risk factors for EDs/DEBs as the general population, which interact with TGD- and Autism-specific risk factors, co-occurring neurodivergence, and sensory processing differences. Evidence about treatment outcomes and the impact of gender-affirming medical care is limited. Given the additional and unique risks for EDs/DEBs in Autistic TGD people, more research is needed in this emerging field. eng.

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39. Xiong H, Xiang X, Liu X, Yang T, Chen J, Chen J, Li T. Predicting autism spectrum disorder severity in children based on specific language milestones: a random forest model approach. Child Adolesc Psychiatry Ment Health. 2025; 19(1): 127.

BACKGROUND: Language impairments are among the most prevalent co-occurring conditions in children with autism spectrum disorder (ASD), and delayed language milestones often serve as early developmental warning signs. However, it remains unclear whether specific language milestones can reliably predict the severity of ASD symptoms, particularly in regions where there is a long delay between initial screening and formal diagnosis. METHODS: This study included 574 children diagnosed with ASD, stratified into two age groups: under 4 years (n = 288) and 4 years or above (n = 286). A total of 33 language milestone items covering receptive, expressive, and pragmatic aspects were evaluated. The Boruta algorithm was applied to identify significant predictors of symptom severity, and random forest models were constructed separately for each age group. Nested cross-validation and grid search were used for hyperparameter tuning. Model performance was assessed using bootstrapping with 1,000 replications to estimate area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 scores. RESULTS: In children under 4 years, 14 features were identified as significant predictors of ASD severity, with « Identifies 1 picture » and « Expresses demands by language » ranked highest. In children aged 4 years and above, 16 features were significant, with « Identifies 2 colors » and « Calls partner by name » being the most influential. The random forest models demonstrated robust predictive performance, with AUC values of 0.81 ± 0.01 (younger group) and 0.85 ± 0.00 (older group). CONCLUSION: Our findings suggest that specific early language milestones, particularly those reflecting pragmatic abilities, may serve as valuable predictors of ASD severity. Leveraging these milestones in clinical practice could support earlier severity stratification and facilitate more tailored intervention planning, particularly in primary care settings.

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