1. Albertini ML, Spoto G, Ceraolo G, Fichera MF, Consoli C, Nicotera AG, Di Rosa G. Sleep Disorders in Children with Autism Spectrum Disorder: Developmental Impact and Intervention Strategies. Brain Sci. 2025; 15(9).

Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in ASD, may further exacerbate these disturbances by affecting arousal regulation and environmental responsiveness during sleep. Given the fundamental role of sleep in brain maturation, its disruption negatively impacts synaptic plasticity and neurological development, particularly during critical periods. These sleep-related alterations can influence cognitive and behavioral outcomes and may serve as early indicators of ASD, highlighting their potential value in early diagnosis and intervention. Understanding the neurobiological mechanisms linking sleep and ASD is essential for developing targeted therapeutic strategies. Ongoing research increasingly focuses on pharmacological, nutraceutical, and behavioral interventions aimed at mitigating sleep disorders and their cascading effects on neurodevelopment. Optimizing these therapeutic approaches through a multidisciplinary lens is crucial for enhancing clinical outcomes and improving overall quality of life in children with ASD.

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2. Aronson JK. When I use a word . . . Paracetamol/acetaminophen-autism and asthma. Bmj. 2025; 390: r2032.

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3. Arturi L, Scoppola C, Riccioni A, Siracusano M, Iasevoli L, Civetta G, Spalletta G, Fiori V, Mazzone L. Application of Concomitant Transcranial Direct Current Stimulation (tDCS) and Cognitive Behavioral-Oriented Training (CBT) for Pragmatic Skills Improvement in Young Adults with Autism Spectrum Disorder (ASD): Preliminary Data from a Pilot Study. Brain Sci. 2025; 15(9).

Objectives: Individuals with Autism Spectrum Disorder (ASD) exhibit difficulties in the social use of language, regardless of age, cognitive abilities, and symptom severity. The left Broca’s area and adjacent cortex are crucial for socio-pragmatic language, particularly in retrieving and integrating context-dependent words. Neuroimaging studies in ASD have shown hypoactivation of the Broca’s area and an aberrant pattern of functional connectivity between language-related regions, suggesting their potential involvement in socio-communicative deficits. Given the potential of tDCS to modulate brain activity, its application targeting Broca’s areas in addition to psychological intervention may represent a promising approach for enhancing socio-communicative skills in ASD. Thus, this study aims to investigate the effect of concomitant anodal tDCS and cognitive behavioral-oriented training (CBT) on pragmatic and communicative skills in young adults with ASD. Methods: A sample of 10 ASD individuals (18-25 years) underwent treatment with both active and sham tDCS targeting the left Broca’s area during concomitant CBT. Each condition was delivered for five consecutive days, and the order of the conditions was blindly randomized. Results: Active tDCS significantly improved global communicative and pragmatic abilities compared to sham. A negative correlation was observed between communicative skills improvement and Intelligence Quotient (IQ); no significant association was found between IQ and ASD symptoms’ severity. Conclusions: Multisession tDCS targeting the left Broca’s area, combined with CBT, may enhance social language in terms of both production and comprehension of non-literal meanings, supporting Broca’s area as a central neural hub for social language.

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4. Atalay S, Çapan Ö Y. Comprehensive in Silico Reclassification of MECP2 Variants of Uncertain Significance in Rett Syndrome: Performance Evaluation and Structural Analysis. J Mol Neurosci. 2025; 75(4): 125.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by missense variants in the MECP2 gene. However, the presence of variants of uncertain significance (VUS) poses major challenges for clinical diagnosis and genetic counseling. In this study, we systematically evaluated the performance of 33 in silico prediction tools using a curated ClinVar dataset of MECP2 missense variants. Performance metrics included accuracy, sensitivity, specificity, area under the curve (AUC), and Matthews correlation coefficient (MCC), incorporating gene-specific pathogenicity thresholds to enhance predictive precision. Evolutionary conservation was assessed using ConSurf, while structural consequences were examined using UniProt, HOPE, DUET, PyMOL, and RING. Nine top-performing tools-MutPred, MetaRNN, REVEL, MutScore, SNPred, BayesDel, ClinPred, AlphaMissense, and DeepSAV-achieved accuracies exceeding 91% and correctly classified all 19 functionally validated pathogenic variants. These tools consistently predicted 15 VUS as pathogenic, with 14 located within the methyl-CpG-binding domain (MBD) and one within the NCOR2/SMRT interaction region; all occurred at highly conserved residues (ConSurf score: 9). Structural analyses revealed destabilizing effects through altered hydrophobicity, electrostatic charge, and residue interactions, implicating impaired DNA binding or disrupted co-repressor interactions. This integrative framework, combining high-performance computational prediction with structural modeling, offers a robust approach to reclassifying MECP2 VUS and supports improved diagnostic accuracy and personalized care in RTT.

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5. Athalye-Jape G, Pillar S, Saminathan S, Wu K, Sherrard S, Dudman E, Sharp M. Evaluation of the Acceptability and Feasibility of the Social Attention and Communication Surveillance-Revised (SACS-R) Tool for Early Identification of Autism in Preterm Infants: The Identify and Act Study. Children (Basel). 2025; 12(9).

INTRODUCTION: Preterm birth is associated with a 3.3-fold increased likelihood of autism diagnosis, with lower gestational age conferring higher likelihood. In Australia, autism is typically diagnosed at around age four, potentially missing the optimal neuroplasticity window before age two. The Social Attention and Communication Surveillance-Revised (SACS-R) tool identifies early autism signs in children aged 11-30 months, enabling pre-emptive intervention. AIMS: This quality improvement (QI) study assessed the acceptability, and feasibility of SACS-R for early detection of autism traits in 12-month-old infants born very preterm/VP (gestation < 32 weeks), from both caregiver and clinician perspectives. METHODS: From September 2024 to February 2025, 47 VP infants attending the 12-month Neonatal Follow-up Clinic (NNFU) at King Edward Memorial Hospital (KEMH), Western Australia, were assessed using SACS-R. Caregivers completed acceptability and feasibility questionnaires; clinicians completed similar surveys. Forty-seven infants met inclusion criteria; 12 clinicians provided responses. RESULTS: Of 47 infants, 4 (8.5%) were identified as having a high likelihood of autism and referred for early intervention. Among caregivers, 29 (61%) provided complete acceptability responses and 28 (59%) feasibility responses, both predominantly positive. Clinicians reported high satisfaction (83%) and ease of use (91%), with 74% supporting routine implementation. Concerns included parental understanding and overlap with other assessments. CONCLUSIONS: Our QI study indicates that the SACS-R is highly acceptable and feasible in neonatal follow-up for preterm infants. Larger-scale evaluation of diagnostic accuracy and practical refinements based on feedback are warranted to support routine integration in early surveillance programs.

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6. Betancort-Avero S, Ferrera-Fernández M, González-de la Torre H, Auyanet-Franchy J, Rodríguez-Suárez CA. Adapting Pediatric Emergency Services for Children with Autism Spectrum Disorder: A Phenomenological Approach. Children (Basel). 2025; 12(9).

Background/Objectives: Children with Autism Spectrum Disorder (ASD) who attend pediatric emergency services face challenges related to their sensory, cognitive, and behavioral characteristics. This study explored the perceptions of healthcare professionals and parents regarding the need to implement adaptations, particularly a sensory-adapted room, for children with ASD in pediatric emergency departments. Methods: A phenomenological qualitative study was conducted through semi-structured interviews (October-December 2024) until data saturation. Participants included healthcare professionals and parents of children diagnosed with ASD. Intentional coding and co-occurrence analysis were performed using Atlas.ti (version 25.0.1). The study was approved by the Research Ethics Committee (code: 204-458-1). Results: Eighteen informants participated (10 professionals and 8 parents). Professionals’ interviews revealed three themes and eight subthemes: Professional Training (approach strategies; training received; perceived needs), Hospital Environment (resource allocation; infrastructure; perceived needs during the emergency visit), and Emotional Aspects (emotional experience related to patient care; professionals’ personal perceptions). Parents’ interviews yielded four themes and ten subthemes: Professional Training (perceptions of staff training; demonstrated emotional competencies; socioemotional relationships during care), Hospital Environment (infrastructure; perceived needs during emergency visits), Emotional Aspects (families’ experiences; emotions during care), and ASD (diagnostic characteristics; children’s needs; sensory regulation). Conclusions: Pediatric emergency services should be adapted to better meet the needs of children with ASD. Both healthcare professionals and parents recognize the importance of such adaptations, particularly sensory-adapted spaces. The main barriers identified were a lack of professional training, inadequate hospital environments, and stress affecting both patients and provider. Priority measures include continuous ASD-specific training programs, improvements in sensory infrastructure, and more flexible clinical protocols, advancing toward a more inclusive and comprehensive model of care.

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7. Boles RG, Bar O, Boles PT, Hill ZR, Frye RE. De Novo Variants Predominate in Autism Spectrum Disorder. Genes (Basel). 2025; 16(9).

BACKGROUND: Autism spectrum disorder (ASD) is a common condition with substantial personal and financial burdens of lifelong implication. Multiple twin studies have confirmed a genetic or inherited component at ~80%, higher than any other common condition. However, ASD’s rapidly accelerating prevalence, now at 1 in 31 in the USA, appears to defy a predominantly genetic basis and implicate our rapidly changing environment. A potential explanation for this paradox is a recent increase in de novo variants (DNVs), which are « new » mutations present in the patient yet absent in both parents. The present authors recently reported using trio whole-genome sequencing (trio-WGS) that DNVs highly likely to be highly disease-associated (« Principal Diagnostic Variants », PDVs), mostly missense variants, were present in (25/50) 50% of the ASD patients clinically evaluated by our team. METHODS: The current study was designed to support this observation with trio-WGS in 100 additional unrelated ASD patients. RESULTS: De novo PDVs were identified in 47/100 (47%) of cases, in close approximation to our previous work. Using non-transcribed (up and downstream) variants for all genes as a control group, these DNV-PDVs were far more likely (p < 0.0001, OR 5.8, 95% C.I. 2.9-11) to be in SFARI-listed genes associated with ASD. Consistent with the emerging polygenic model, using the same analyses, inherited missense variants were also associated with ASD (p < 0.0001). Highly unexpectedly, silent variants, both inherited (p < 0.0001) and de novo (p < 0.007), were also statistically associated with ASD, and, among inherited variants, silent variants were more associated with ASD than were missense variants (p < 0.0001). Adding silent DNVs as PDVs increases the proportion of our subjects with at least one DNV-PDV to 55% of the subjects. CONCLUSIONS: Our proposed model for ASD, with prominent DNVs in most that are genetic yet not inherited, predicts the known predominant genetic pathogenesis and the accelerating prevalence of ASD, possibly from environmental factors, including insufficient nutrients and toxicant exposures, and/or the disrupted folate metabolism known to be associated with ASD. Limitations to this study include predominant inclusion of severely affected individuals and the lack of an unaffected control group and functional validation of variant pathogenicity.

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8. Cai M, Dai Y, Duan M, Chen M, Ji Y, Zhou L, Chen L, Zhang L. Intervention adherence and its predictors among parents of children with autism spectrum disorder. J Pediatr Nurs. 2025; 85: 549-57.

AIMS: To investigate the intervention adherence among parents of children with Autism Spectrum Disorder (ASD) and explore its predictors. METHODS: In this cross-sectional study, a total of 209 parents of children with ASD were recruited from a tertiary hospital in Guangzhou, China, from September 2022 to August 2023. Treatment Compliance Scale (TCS), Autism Behavior Checklist (ABC), Parenting Sense of Competence Scale (PSOC), and Parenting Stress Index-Short Form (PSI-SF) were used for data collection. Multiple linear regression analysis was performed to explore the predictors of intervention adherence. RESULTS: The TCS score was 60.18 ± 12.81, and the item mean scores of professional treatment, family intervention and regular follow-up were 3.73 ± 1.02, 2.98 ± 0.80 and 3.65 ± 0.93, respectively. Multiple linear regression analysis showed that fathers’ educational level (β = 0.272, P < 0.01), mothers' daily time with children (β = 0.257, P < 0.05), sensory domain in ABC (β = 0.146, P < 0.05), parenting self-efficacy (β = 0.229, P = 0.001) and parenting satisfaction (β = 0.152, P < 0.05) statistically significantly predicted TCS, accounting for 24.7 % of the variance [F (P) = 6.256, P < 0.001]. CONCLUSION: Intervention adherence among parents of children with ASD was at a moderate level. Parenting confidence (self-efficacy and satisfaction), fathers' education level, mothers' daily time with children, and children's sensory processing abnormalities significantly predicted adherence. These findings suggest that targeted interventions focusing on enhancing parental confidence and providing tailored support based on family characteristics may improve parents' intervention adherence.

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9. Chistiakov S, Dolganov A, Constable PA, Zhdanov A, Kulyabin M, Thompson DA, Lee IO, Albasu F, Borisov V, Ronkin M. Time Series Classification of Autism Spectrum Disorder Using the Light-Adapted Electroretinogram. Bioengineering (Basel). 2025; 12(9).

The clinical electroretinogram (ERG) is a non-invasive diagnostic test used to assess the functional state of the retina by recording changes in the bioelectric potential following brief flashes of light. The recorded ERG waveform offers ways for diagnosing both retinal dystrophies and neurological disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Parkinson’s disease. In this study, different time-series-based machine learning methods were used to classify ERG signals from ASD and typically developing individuals with the aim of interpreting the decisions made by the models to understand the classification process made by the models. Among the time-series classification (TSC) algorithms, the Random Convolutional Kernel Transform (ROCKET) algorithm showed the most accurate results with the fewest number of predictive errors. For the interpretation analysis of the model predictions, the SHapley Additive exPlanations (SHAP) algorithm was applied to each of the models’ predictions, with the ROCKET and KNeighborsTimeSeriesClassifier (TS-KNN) algorithms showing more suitability for ASD classification as they provided better-defined explanations by discarding the uninformative non-physiological part of the ERG waveform baseline signal and focused on the time regions incorporating the clinically significant a- and b-waves of the ERG. With the potential broadening scope of practice for visual electrophysiology within neurological disorders, TSC may support the identification of important regions in the ERG time series to support the classification of neurological disorders and potential retinal diseases.

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10. Corcione A, Del Giudice LA, Basilicata S, Maglio M, Aiello S, Cerchione R, Annunziata A, Amaddeo A, Borrelli M. Managing Complexity in Rett Syndrome with a Focus on Respiratory Involvement: A Tertiary Center Experience. Children (Basel). 2025; 12(9).

BACKGROUND: Rett syndrome (RS) is a rare neurodevelopmental disorder primarily affecting females, characterized by severe neurological impairment and complex comorbidities, including epilepsy, scoliosis, and respiratory dysfunction. Respiratory complications, such as recurrent infections and sleep-disordered breathing (SDB), are increasingly recognized as significant contributors to morbidity. This study aimed to evaluate the prevalence, severity, and management of major comorbidities-including epilepsy, scoliosis, respiratory infections, and SDB-in a pediatric cohort with genetically confirmed RS. METHODS: We conducted a retrospective review of medical records from 23 female patients under 18 years of age with MECP2 mutations, referred to our tertiary care center from 2021 to 2025. Data on epilepsy, scoliosis, respiratory infections, and nutritional status were collected. The presence of SDB was assessed through overnight home polygraphy (oPG) and transcutaneous carbon dioxide monitoring in selected cases. RESULTS: Epilepsy affected 65% of patients, all with good seizure control. Scoliosis was present in 52%, with two patients requiring spinal surgery. At least one episode of lower respiratory tract infection (LRTI) was presented in 39% of our girls. LRTIs positively correlated with the number of hospitalization and antibiotic treatment. Among patients undergoing oPG, 67% presented obstructive sleep apnea, with its severity positively correlating with the frequency of lower respiratory infections. Severe nocturnal hypercapnia was documented in three patients, leading to non-invasive or invasive ventilation. CONCLUSIONS: Our findings highlight the high prevalence of sleep-related respiratory disorders and their association with respiratory infections in children with RS. Systematic respiratory assessment, including sleep studies, and early implementation of airway clearance techniques and ventilatory support are crucial to improving clinical outcomes in this vulnerable population.

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11. de Angeli LRA, Serafim BLC, Masquijo JJ. The Autistic Toe Walking: A Narrative Review for Interventions and Comparison with Idiopathic Toe Walking. Children (Basel). 2025; 12(9).

BACKGROUND/OBJECTIVES: Idiopathic toe walking (ITW) is a diagnosis of exclusion in children who demonstrate a persistent toe-walking gait without an identifiable underlying neuromuscular or orthopedic pathology. The classification of toe-walking behavior (TWB) in children with Autism Spectrum Disorder (ASD) remains an area of debate, with some considering it a part of the broader ITW spectrum, while others view it as a distinct entity. Children with TWB associated with ASD (Autistic Toe Walking-ATW) present unique clinical challenges. This subgroup exhibits a higher prevalence of toe walking, and their gait patterns are often associated with underlying neurodevelopmental differences, frequently leading to increased resistance to conventional treatment approaches and higher rates of persistence and recurrence. This narrative review aims to summarize the available evidence on interventions for ATW, highlight differences compared to ITW and discuss implications for clinical practice. METHODS: A literature search was performed, including articles that addressed interventions for toe walking in children with ASD. RESULTS: The literature is limited and heterogeneous. Identified interventions include physiotherapy, orthoses, botulinum toxin injections, serial casting, and surgical procedures. Evidence of effectiveness is scarce, with most studies consisting of small case series. ATW differs from classic ITW in some aspects of pathophysiology and clinical presentation. Treatment decisions should balance potential benefits with risks, particularly regarding repeated anesthesia exposure during casting versus earlier surgical options. CONCLUSIONS: Evidence for managing ATW is limited. While comparisons to ITW may be useful, clinicians must recognize that they present distinct characteristics. Future research should focus on standardized definitions and controlled trials to guide management.

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12. Erarkadaş M, Özmeral Erarkadaş K, Şişmanlar Ş G. Psychiatric symptoms and their predictors in aging parents of adults with autism spectrum disorder. Sci Rep. 2025; 15(1): 33036.

Parenting an individual with Autism Spectrum Disorder (ASD) affects the mental health of both mothers and fathers. A chronic disorder, ASD, has devastating effects on parental mental health as the affected individual moves from childhood to adulthood. While the effects of ASD on parental mental health during childhood have been studied extensively, there is limited information regarding the mental health of aging parents of the expanding adult ASD population. In this context, we aimed to determine the psychiatric symptoms (PS) levels of parents of adult with ASD, to compare the PS level between mothers and fathers, to investigate the relationship between parental PS and variables related to the individuals with ASD and their parents. To assess the parents’ PS, the Brief Symptom Inventory was administered to 77 parents of adults with ASD. ASD severity was evaluated with the Childhood Autism Rating Scale, behavioral problems were assessed with the Aberrant Behavior Checklist, independence level (IL) of the cases was measured with the Lawton Instrumental Activities of Daily Living Scale, and social functioning level (SFL) of the cases was evaluated using the Social Functioning Scale. At all ages from childhood to adulthood, the most common primary caregiver was mother. Mothers’ labor force participation rate was significantly lower than fathers’ (p < 0.05). Mothers' somatization (p = 0.028) and depression (p = 0.002) levels were significantly higher than fathers'. The somatization score of the mothers of cases with comorbid medical diagnosis and intellectual disability (ID) was significantly higher than those without. The depression score of fathers of cases with ID and illiteracy was significantly higher (p < 0.05). The negative self-concept score of fathers of cases with ID, illiteracy, and dependent self-care and toileting was significantly higher (p < 0.05). As IL increased, paternal depression and negative self-concept levels decreased significantly (p < 0.05). When SFL increased, maternal anxiety, depression, and somatization and paternal negative self-concept levels decreased significantly (p < 0.05). In regression analyses, maternal anxiety was significantly associated with irritability, depression with hyperactivity, negative self-concept with irritability; somatization with irritability and the presence of medical diease in mother and patient; hostility with hyperactivity. Paternal anxiety, depression, somatization, and hostility were associated with irritability; negative self-concept with irritability and social withdrawal. It is hoped these results contribute to a better understanding of the protective and risk factors of the psychopathology of parents of adults with ASD, a topic relatively poorly studied.

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13. Eroğlu G. Electroencephalography-Based Machine Learning for Biomarker Detection in Dyslexia and Autism Spectrum Disorder: A Comparative Review of Models, Features, and Diagnostic Utility. Diagnostics (Basel). 2025; 15(18).

To uncover neurobiological indicators related to autism spectrum disorders and developmental dyslexia, this article gives a full overview of the most recent advances in machine learning and deep learning methods based on electroencephalography. We look into methodological pipelines that include signal gathering, preprocessing, feature engineering, model selection, and interpretability procedures. We based these pipelines on 15 peer-reviewed research papers published between 2013 and 2025. Most of the research employed the 10-20 system for resting-state EEG and followed MATLAB, MNE-Python, or EEGLAB guidelines for preprocessing. The feature sets included spectral power, functional connectivity, task-evoked potentials, and entropy measures. People used many standard ML methods, such as support vector machines and random forests, as well as more advanced models, like deep neural networks and transformer-based architectures. Several studies found that both dyslexic and ASD groups did well at classifying, with accuracy scores between 82% and 99.2%. The new models could be used in therapeutic settings, but there are still problems with how easy they are to understand and how well they apply to a wide range of situations. This is especially true for ASD because its spectrum is so varied.

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14. Fahmi F, Melinda M, Purnamasari PD, Elizar E, Rafiki A. Recognition of EEG Features in Autism Disorder Using SWT and Fisher Linear Discriminant Analysis. Diagnostics (Basel). 2025; 15(18).

Background/Objectives: An ASD diagnosis from EEG is challenging due to non-stationary, low-SNR signals and small cohorts. We propose a compact, interpretable pipeline that pairs a shift-invariant Stationary Wavelet Transform (SWT) with Fisher’s Linear Discriminant (FLDA) as a supervised projection method, delivering band-level insight and subject-wise evaluation suitable for resource-constrained clinics. Methods: EEG from the KAU dataset (eight ASD, eight controls; 256 Hz) was decomposed with SWT (db4). We retained levels 3, 4, and 6 (γ/β/θ) as features. FLDA learned a low-dimensional discriminant subspace, followed by a linear decision rule. Evaluation was conducted using a subject-wise 70/30 split (no subject overlap) with accuracy, precision, recall, F1, and confusion matrices. Results: The β band (Level 4) achieved the best performance (accuracy/precision/recall/F1 = 0.95), followed by γ (0.92) and θ (0.85). Despite partial overlap in FLDA scores, the projection maximized between-class separation relative to within-class variance, yielding robust linear decisions. Conclusions: Unlike earlier FLDA-only pipelines and wavelet-entropy-ANN approaches, our study (1) employs SWT (undecimated, shift-invariant) rather than DWT to stabilize sub-band features on short resting segments, (2) uses FLDA as a supervised projection to mitigate small-sample covariance pathologies before classification, (3) provides band-specific discriminative insight (β > γ/θ) under a subject-wise protocol, and (4) targets low-compute deployment. These choices yield a reproducible baseline with competitive accuracy and clear clinical interpretability. Future work will benchmark kernel/regularized discriminants and lightweight deep models as cohort size and compute permit.

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15. Frye RE, Hill Z, Rose S, McCullough S, Porter-Gill PA, Gill PS. Transcriptomic Signatures of Mitochondrial Dysfunction in Autism: Integrated mRNA and microRNA Profiling. Genes (Basel). 2025; 16(9).

BACKGROUND: Prior work established that about a third of ASD-derived LCLs show excessive mitochondrial respiration and stress vulnerability-features divergent from both controls and classical mitochondrial disease. This study explores how mRNA and microRNA (miRNA) expression profiles distinguish subtypes of autism spectrum disorder (ASD) defined by mitochondrial function. METHODS: Lymphoblastoid cell lines (LCLs) from boys with ASD were classified into two groups: those with abnormal (AD-A) and normal (AD-N) mitochondrial function. RNA-seq compared mRNA and miRNA expression differences. RESULTS: 24 mRNA differentially expressed genes (DEGs) (14 downregulated, 10 upregulated in AD-N vs. AD-A) were identified, implicating processes such as mRNA processing, immune response, cancer biology, and crucially, mitochondrial and nuclear activities. Notably, genes such as DEPTOR (an mTOR modulator) were upregulated in AD-A, highlighting dysregulation in the mTOR pathway-a central regulator of cellular metabolism, protein synthesis, autophagy, and mitochondrial function. miRNA analysis revealed 18 differentially expressed miRNAs (DEMs) upregulated and one downregulated in AD-N compared to AD-A. Several miRNAs (including hsa-miR-1273h-3p, hsa-miR-197-3p, and hsa-miR-199a-5p) targeted both the differentially expressed genes and pathways previously linked to ASD, such as mTOR, Calmodulin Kinase II, and mitochondrial regulation. Enrichment analyses indicated involvement regulation of cell growth and division, gene expression, immune regulation and cellular stress as well as mTOR signaling. CONCLUSIONS: These molecular signatures support the idea that mitochondrial dysfunction in ASD is tied to specific disruptions in the mTOR and PI3K/AKT signaling axes, influencing cell growth, autophagy, oxidative stress handling, and neuronal metabolism. The findings highlight a miRNA-mRNA regulatory network that may underpin mitochondrial dysfunction and ASD heterogeneity, suggesting avenues for subtype-specific biomarkers and targeted therapies that address energy metabolism and cellular stress in ASD.

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16. Genovese AC, Butler MG. PTEN Gene and Autism: Genetic Underpinnings and Neurodevelopmental Impacts. Genes (Basel). 2025; 16(9).

Background/Objectives: Twin and family studies suggest that 90% of the risk for autism spectrum disorder (ASD) is due to genetic factors, with 800 genes recognized as playing a role. An important gene is phosphatase and tensin homolog (PTEN), which plays a significant role in cancer as a tumor suppressor best known for causing overgrowth and PTEN hamartoma tumor syndromes (PHTS). Less well known are PTEN germline mutations with adverse neurodevelopmental impacts of macrocephaly, intellectual disability, and ASD, as well as other behavioral and psychiatric disturbances. There remains a limited understanding of whether these gene variants are associated with differing manifestations of PTEN-associated neurodevelopmental disorders. Methods: This review utilized comprehensive literature searches such as PubMed, OMIM, and Gene Reviews with keywords of PTEN, genetic factors, autism, and human studies and by searching genomic-protein functional networks with STRING computer-based programs for functional and genetic mechanisms. Results: This review explored the genetic underpinnings of PTEN gene variants causing altered interactive proteins and their mechanisms, biological processes, molecular functions, pathways, and disease-gene associations. We characterized specific gene-gene or protein-protein interactions and their functions relating to neurodevelopment, psychiatric disorders, and ASD that were found to be increased with PTEN gene variants. Conclusions: PTEN gene defects are among the most recognized genetic causes of ASD. PTEN gene variants and altered protein interactions and mechanisms described in our study are associated with an increased risk for tissue and organ overgrowth, macrocephaly, and distinct brain anomalies, specifically newly identified abnormal CSF dynamics. These genetic underpinnings and impacts on neurodevelopment are discussed. The genetic and protein findings identified may offer clues to effective treatment interventions, particularly when instituted at a young age, to improve long-term outcomes.

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17. Gesi C, Pisani R, Tamburini N, Dell’Osso B. The Relationship Between Camouflaging and Lifetime Depression Among Adult Autistic Males and Females. Brain Sci. 2025; 15(9).

Objective: We aimed to investigate the relationship between camouflaging and lifetime depression among autistic people, along with the role of sex in this relationship. Methods: Sixty-five autistic subjects with no intellectual or language disability (34 females, 31 males), presenting to an outpatient service for the treatment of concurrent mental disorders, were administered module A of the Structured Clinical Interview for DSM-5 Disorders, the Autism Spectrum Quotient (AQ), and the Camouflaging Autistic Traits Questionnaire (CAT-Q). Results: No differences were found in CAT-Q total or domain scores across sexes. Subjects with lifetime depression reported significantly higher scores than those without for all CAT-Q scores, with depressed women often reporting the highest scores among the groups. The difference between depressed and non-depressed women was significant for all but the CAT-Q assimilation score. The CAT-Q total score significantly predicted lifetime depression (B = 0.053, p = 0.003) when controlling for age, sex, and the AQ total score. Conclusions: Our study expands the extant knowledge about the role of camouflaging in the mental wellbeing of autistic people by showing a correlation between camouflaging and depressive disorders throughout the lifetime among both males and females.

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18. Grahame V, Kernohan A, Kharati E, Mathias A, Butcher C, Dixon L, Fletcher-Watson S, Garland D, Glod M, Goodwin J, Heron S, Honey E, Le Couteur A, Mackie L, Ogundimu E, Probert H, Riby D, Rob P, Rogan L, Tavernor L, Vale L, Imogen Webb E, Weetman C, Rodgers J. A group intervention for parents and carers to recognise and understand restricted and repetitive behaviour in autistic children: a multisite RCT. Health Technol Assess. 2025; 29(48): 1-88.

BACKGROUND: Restricted and repetitive behaviours vary greatly between autistic people. Some are a source of pleasure or create opportunities for learning; however, others are functionally impactful and may cause harm. We have developed a parent/carer group intervention (Understanding Repetitive Behaviours), for families of young autistic children, to help parents/carers to recognise, understand and respond to their child’s functionally impactful restricted and repetitive behaviours. OBJECTIVES: To evaluate the clinical and cost-effectiveness of the Understanding Repetitive Behaviours intervention. DESIGN: A clinical and cost-effectiveness, multisite randomised controlled trial of the Understanding Repetitive Behaviours intervention versus a psychoeducation parent/carer group Learning About Autism (n = 250; 125 intervention/125 psychoeducation; ~ 83/site). Analyses completed using intention-to-treat principles. SETTING: Three NHS trusts and universities across England and Scotland. PARTICIPANTS: Parents/carers aged 18 and over, with an autistic child between 3 and 9 years and 11 months, sufficient spoken and written English, willing to be randomised and attend all group sessions, who agree to maintain their child’s current medication up to 24 weeks and not to participate in any other trials up to 24 weeks. INTERVENTION: An 8-week parent/carer intervention that was delivered face to face and online using a secure digital platform. Randomisation was at the child level using equal allocation ratio. INFORMATION: Research associates and research leads were blind to trial arm allocation. MAIN OUTCOME MEASURES: The primary outcome is the Clinical Global Impression – Improvement scale, based on child data. Economic outcomes included incremental cost per additional child achieving at least the target improvement in Clinical Global Impression – Improvement scale, cost consequences and incremental cost per quality-adjusted life-year gained were calculated for the comparison of the Understanding Repetitive Behaviours and Learning About Autism groups. RESULTS: Two hundred and sixty-two participants were consented and 227 randomised to either the Learning About Autism (113 participants) or the Understanding Repetitive Behaviours (114 participants) arms of the trial. Seventy-two families did not provide data at primary end point. Data were available for 81 Learning About Autism and 74 Understanding Repetitive Behaviours families at 24 weeks. No differences were found between the arms on the Clinical Global Impression – Improvement scale. Analysis of the secondary outcomes indicated that children in the Understanding Repetitive Behaviours arm were more likely to be rated responders in target restricted and repetitive behaviours at 24 weeks. Improvement in parent and family functioning was apparent across both arms over time, with no evidence of differences between the arms. Five serious adverse events were reported, none of which were related to study participation. CONCLUSIONS: The study had a less than expected follow-up at the primary end point and was therefore underpowered. Findings related to the potential clinical effectiveness of Understanding Repetitive Behaviours remain inconclusive. Understanding Repetitive Behaviours is unlikely to be considered cost-effective at 12 months. Future work should determine what the mechanisms of change in functionally impactful restricted and repetitive behaviours are and consider longer time horizons and different methods of valuing benefits for autistic children. TRIAL REGISTRATION: This trial is registered as ISRCTN15550611. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/111/95) and is published in full in Health Technology Assessment; Vol. 29, No. 48. See the NIHR Funding and Awards website for further award information. Autistic children often do the same behaviours repeatedly, have specific interests or like things to stay the same each time something happens. Often this does not cause difficulties and these behaviours and interests can be helpful and fun. However, sometimes they may cause harm to the child, put them at risk and/or restrict opportunities for learning or impact on their family life. Working with parents/carers of autistic children, we developed a parent/carer programme (Understanding Repetitive Behaviours) to help parents/carers to recognise and understand these behaviours and learn approaches to reduce their child’s use of behaviours that have a functional impact. This study aimed to find out whether our parent programme was helpful and good value for money. The 227 families who agreed to participate in the study were allocated by chance into two separate groups, either the Understanding Repetitive Behaviours group or another parent/carer group (Learning About Autism). Parents/carers provided us with lots of information about their child and themselves at the beginning of the study, and then again after 10, 24 and 52 weeks. This study took place during the COVID-19 pandemic, and we had to make changes to both the delivery of parent programmes and how the research took place to comply with government guidelines. Unfortunately, 72 families did not complete the follow-up at 24 weeks. This meant that we were unable to find out whether or not the Understanding Repetitive Behaviours intervention was effective. We therefore cannot recommend either parent group intervention to help parents know how best to respond to their autistic child’s impactful repetitive behaviours. Despite this, we were able to show that both Understanding Repetitive Behaviours and Learning About Autism can be delivered by trained NHS professionals and that both groups are safe for families. Also, some families who attended Understanding Repetitive Behaviours reported improvement in their child’s functionally impactful repetitive behaviours at 24 weeks and parents/carers in both groups reported more confidence, greater well-being and less stress up to 1 year afterwards, indicating that both parent groups were beneficial and supportive for parents of autistic children. eng.

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19. Gualtieri C, Smith ZM, Cruz A, Khan Z, Jenkins C, Mishra-Gorur K, Vonhoff FJ. Dysregulation of Protein Kinase CaMKI Leads to Autism-Related Phenotypes in Synaptic Connectivity, Sleep, Sociality, and Aging-Dependent Degeneration in Drosophila. Biology (Basel). 2025; 14(9).

Autism spectrum disorder (ASD) encompasses a range of conditions, primarily marked by deficits in social behaviors, along with several comorbidities such as sleep abnormalities and motor dysfunction. Recent studies have identified genetic risk factors associated with ASD, including the CAMK4 (calcium/calmodulin-dependent protein kinase 4). However, the molecular mechanisms linking CAMK4 dysregulation and ASD-associated phenotypes remain poorly understood. Here, we used Drosophila melanogaster as a model system to investigate ASD-associated phenotypes in flies with dysregulated CaMKI, the fly homolog of mammalian CAMK4. We show that CaMKI manipulations affect sleep, circadian rhythmicity, and social behavior. Consistent with the higher prevalence of dementia observed in autistic patients, we also observed a significantly enhanced behavioral decline in motor performance and dendritic degeneration in flies expressing RNAi-based CaMKI knockdown in flight motoneurons, suggesting a link between developmental and degenerative processes. As aberrant synaptic pruning is hypothesized to underlie the synaptic phenotypes observed in brains of autistic patients, we examined synaptic phenotypes following CaMKI manipulations using the larval neuromuscular junction (NMJ) and observed miswiring phenotypes suggesting aberrant synaptic refinement. We performed shotgun mass-spectrometry proteomics and identified various molecular candidates, particularly molecules involved in cytoskeleton regulation and chemorepulsion, likely to regulate the phenotypes described here. Thus, our results suggest that CaMKI plays a role in developmental processes and influences aging-dependent degenerative processes, possibly providing mechanistic insight into the genetic basis of ASD etiology and the development of effective treatments.

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20. Hsieh IH, Hsiao ZH. Assessing the relationship between absolute pitch and autistic traits using a novel continuous slider scale. BMC Psychol. 2025; 13(1): 1048.

BACKGROUND: Evidence regarding the link between absolute pitch (AP) and autistic traits is currently inconclusive. Previous subclinical measurements of autistic traits using discrete response options may mask subtle variations, contributing to discrepancies between studies. This study employs a novel slider for continuous measurements to reveal AP-related subtle variations along autistic traits that discrete scales might overlook. METHODS: We contrasted autistic traits measured using a novel continuous slider with those measured using a traditional discrete scale in a larger sample (N = 120) than previous similar studies, with musicians and non-musicians stratified into high, medium, and low-AP proficiency groups. Data were collected between July 2023 and April 2024. Participants indicated their agreement/disagreement on the Autism spectrum Quotient (AQ) either (i) discretely by selecting from four fixed choices or (ii) continuously by adjusting a visual slider along a 0 to 100% continuum. Additionally, cognitive tasks associated with AP ability, including pitch adjustment, musical proficiency, and relative pitch ability, were assessed. RESULTS: A significant correlation between conventionally measured autistic traits and slider adjustments validated the slider’s efficacy. A higher autistic score in AP musicians was revealed across social/communication domains using continuous relative to discrete scales. Notably, continuous measurement identified a heightened autistic trait in the AQ subscale imagination in AP musicians that was not found in discrete measures. Among all cognitive abilities assessed in AP musicians, only pitch-related skills predicted autistic traits, suggesting similarly enhanced pitch functions. CONCLUSION: These findings support the hypothesized link between AP and autistic traits, highlighting the need for further validation of continuous measurement scales to better understand the co-occurrence of specific human traits.

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21. Iqbal Z, Rahman MM, Zia Q, Popov P, Fu Z, Calhoun VD, Plis S. Interpretable Disorder Signatures: Probing Neural Latent Spaces for Schizophrenia, Alzheimer’s, and Autism Stratification. Brain Sci. 2025; 15(9).

OBJECTIVE: This study aims to develop and validate an interpretable deep learning framework that leverages self-supervised time reversal (TR) pretraining to identify consistent, biologically plausible functional network biomarkers across multiple neurological and psychiatric disorders. METHODS: We pretrained a hierarchical LSTM model using a TR pretext task on the Human Connectome Project (HCP) dataset. The pretrained weights were transferred to downstream classification tasks on five clinical datasets (FBIRN, BSNIP, ADNI, OASIS, and ABIDE) spanning schizophrenia, Alzheimer’s disease, and autism spectrum disorder. After fine-tuning, we extracted latent features and employed a logistic regression probing analysis to decode class-specific functional network contributions. Models trained from scratch without pretraining served as a baseline. Statistical tests (one-sample and two-sample t-tests) were performed on the latent features to assess their discriminative power and consistency. RESULTS: TR pretraining consistently improved classification performance in four out of five datasets, with AUC gains of up to 5.3%, particularly in data-scarce settings. Probing analyses revealed biologically meaningful and consistent patterns: schizophrenia was associated with reduced auditory network activity, Alzheimer’s with disrupted default mode and cerebellar networks, and autism with sensorimotor anomalies. TR-pretrained models produced more statistically significant latent features and demonstrated higher consistency across datasets (e.g., Pearson correlation = 0.9003 for schizophrenia probing vs. -0.67 for non-pretrained). In contrast, non-pretrained models showed unstable performance and inconsistent feature importance. CONCLUSIONS: Time Reversal pretraining enhances both the performance and interpretability of deep learning models for fMRI classification. By enabling more stable and biologically plausible representations, TR pretraining supports clinically relevant insights into disorder-specific network disruptions. This study demonstrates the utility of interpretable self-supervised models in neuroimaging, offering a promising step toward transparent and trustworthy AI applications in psychiatry.

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22. Jung M, Han KS. The Attachment Process of the Mothers of Children with Autism Spectrum Disorders in the Pre-School Years: A Mixed Methods Study. Children (Basel). 2025; 12(9).

BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is characterized by qualitative difficulties in interaction and communication, as well as hyper- or hypo-responsivity to sensory input, which can substantially challenge the formation of mother-child attachment. This study aimed to identify attachment levels among mothers of preschool-aged children with ASD and to delineate the attachment processes associated with those levels, with the goal of developing a grounded theory explaining these processes. METHODS: A two-step study using methodological triangulation was conducted. In the first quantitative study, the attachment level of 64 mothers of children with ASD, under the age of 7 years in Korea, were measured. And 12 were selected for a second study using the grounded theory method of Strauss & Corbin. RESULTS: A significant attachment difference (t = 4.39, p < 0.001) was found in the pregnancy plan. The core attachment category in mothers of pre-school children with ASD was identified as "keep on going with closing the distance". Eight stages and four types were found in their attachment process. CONCLUSIONS: The results of this suggest that it is necessary to develop a personalized intervention strategy and to provide proper nursing by considering the attachment process and type of mothers of children with ASD.

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23. Kabarite A, Ferreira GMM, Pitangueira JC, Arimatéa RS, da Costa Rebello de Mendonça R, Marcello RS, Schulz TG, Riesgo RDS, Castro K. A Longitudinal Transdisciplinary Approach for Autism Spectrum Disorder. Children (Basel). 2025; 12(9).

Background/Objectives: Autism Spectrum Disorder (ASD) presents complex developmental challenges that require coordinated, individualized interventions. This study aimed to evaluate the effectiveness of a transdisciplinary, family-centered approach in improving clinical and functional outcomes in children and adolescents with ASD. Methods: A longitudinal study was conducted with 53 participants aged 2 to 16 years, all with confirmed ASD diagnoses. Assessments were performed at baseline, 6 months, and 12 months. Participants received personalized, evidence-based interventions provided by a multidisciplinary team working within a transdisciplinary model. Therapies were delivered individually and in groups, with flexible intervention phases tailored to each participant’s evolving needs. Outcomes were measured using the Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and the Aberrant Behavior Checklist (ABC). Results: Clinical and functional improvements were observed over the 12-month period. Most participants reached high functional levels by the end of the study. Caregivers reported notable reductions in support needs, while therapist ratings confirmed more moderate improvements. Decreases in behavioral challenges, sensory difficulties, and sleep disturbances were observed, alongside gains in adaptability and functional play. Greater family involvement was associated with more favorable outcomes. Conclusions: A transdisciplinary, family-centered intervention model was beneficial in supporting developmental progress in children and adolescents with ASD. The findings highlight the importance of flexible, team-based care and emphasize the critical role of family engagement in achieving positive long-term outcomes.

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24. Kumazaki H, Ohnishi Y, Sumioka H, Shiomi M. Role-play-based hug-robot-mediated communication in promoting friendship among individuals with autism spectrum disorders. Asian J Psychiatr. 2025; 112: 104704.

Individuals with autism spectrum disorder (ASD) often experience challenges in building friendships across the lifespan. To address the limitations of existing hug-based interventions, we developed Moffuly-MS, a tele-operated interactive hugging robot. In this study, participants were paired and alternated roles using Moffuly-MS; one person operated the robot to deliver a hug, while the other received it, and they took turns playing both roles. This study aimed to evaluate whether bidirectional haptic interaction via Moffuly-MS could improve mutual understanding and promote a sense of oneness. Twenty-four individuals (20 males and four females) participated over 6 consecutive days. In the with-hug condition, post-intervention scores significantly improved from baseline in both knowledge of partner (t (22) = 3.873, p = .005, r = .64) and sense of oneness (t (22) = 3.182, p = .013, r = .57). A Wilcoxon signed-rank test revealed that perceived relaxation in the hug condition was significantly higher than that in the without-hug condition (z = 2.377, p = 0.017, r = 0.49). The results indicated that participants demonstrated enhanced knowledge of their partner and a greater sense of oneness following the intervention. These findings suggest that our approach may promote social connectedness in individuals with ASD. Future research with larger, more diverse samples and longitudinal designs is needed to confirm and expand upon these results.

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25. Labarca P, Oyanadel C, González-Loyola M, Peñate W. Effective Interventions in the Treatment of Self-Harming Behavior in Children and Adolescents with Autism Spectrum Disorder: A Review. Children (Basel). 2025; 12(9).

Background/Objectives: Autism spectrum disorder (ASD) is frequently associated with self-injurious behaviors, posing significant risks to individuals and considerable challenges for families and professionals. While various interventions have been proposed, evidence regarding their relative effectiveness remains fragmented. The general aim of this study was to perform a narrative review to analyze effective non-pharmacological interventions targeting self-injurious behaviors (SIBs) in autistic children and adolescents, addressing the following research question: Which non-pharmacological interventions are effective in reducing self-injurious behaviors in autistic children and adolescents, and under what conditions? The review focused on identifying treatment types, contexts of implementation, and outcome efficacy. Methods: This review was conducted based on a search in WoS, SCOPUS and PubMed databases. According to the PICOS criteria, we included studies involving children and adolescents with ASD and interventions for self-injurious behaviors. We compared different types of interventions and evaluated outcomes in terms of reduction in SIBs. Eligible studies were those reporting quantitative or qualitative outcomes on SIB interventions, published within the past 10 years. Results: Thirteen studies met the inclusion criteria. The interventions included applied behavior analysis (ABA), cognitive behavioral therapy (CBT), sensory integration therapy, and pharmacology. The reported outcomes generally indicated reductions in the frequency and severity of self-injurious behaviors. However, many studies lacked long-term follow-up data, and few addressed the generalization of treatment effects. Methodological variability limited both the comparability across studies and the generalization of results. Conclusions: This review emphasized a multidisciplinary, individualized approach to treating self-injurious behaviors in autistic youth. ABA emerged as the most effective intervention, while CBT proved beneficial for higher-functioning adolescents, and sensory therapies addressed specific challenges. Combined treatments showed promise, and family involvement and long-term research remain essential.

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26. Leisman G, Melillo R. Autism Spectrum Disorder: What Do We Know and Where Do We Go?. Brain Sci. 2025; 15(9).

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that manifests in early childhood and persists throughout an individual’s life. Characterized by a range of symptoms affecting social interaction, communication, and behavior, ASD presents a spectrum of varying degrees of severity and presentation. Recent research emphasizes the importance of understanding the diverse manifestations of ASD across different populations. Core features include social communication differences and restricted and repetitive behaviors (RRBs), often linked to co-occurring conditions such as anxiety and ADHD. The study of ASD has evolved significantly, highlighting the need for individualized approaches to diagnosis and intervention. This paper explores current knowledge on ASD, examining the latest research findings and discussing future directions for improving the lives of those affected by the disorder. The purpose is to present a map of the field and an evidence-strength framing of what is known and unknown, and where the evidence is equivocal. Key areas of focus include behavioral, psychological, genetic, metabolic, immunological, and neurological features, as well as developmental and maturational factors. The aim is to provide a comprehensive overview of what is known, what remains unclear, and where future research should be directed.

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27. McGuire R, Nico J, Nattress N, Irizarry-Pérez C, Gevarter C. Coaching Bilingual Speech-Language Student Clinicians and Spanish-Speaking Caregivers to Use Culturally Adapted NDBI Techniques with Autistic Preschoolers. Behav Sci (Basel). 2025; 15(9).

A cascading coaching model was used to teach bilingual speech-language pathology (SLP) graduate student clinicians and Spanish-speaking caregivers to implement naturalistic developmental behavioral intervention (NDBI) techniques with autistic preschoolers. Two triads (each consisting of a graduate student clinician, a minimally vocal child diagnosed with autism, and a caregiver) participated in the study. Following the cascading approach, a lead instructor (with limited Spanish conversational skills) coached bilingual student clinicians (in English) to apply culturally adapted NDBI with child participants. Following additional instruction in coaching, student clinicians coached caregivers in Spanish. Effects were evaluated using a multiple methods approach consisting of multiple probes across participants single case experimental design and a qualitative analysis of semi-structured interviews with adult participants. All adult participants increased their use of targeted NDBI skills including elicitation techniques (creating communication temptations, using wait time, and prompting) and response techniques (reinforcing children’s communication with natural consequences and providing a contextually relevant vocal model), demonstrating large to very large effect sizes. Although qualitative findings indicated areas for improvement (e.g., additional Spanish supports for clinicians), thematic analysis revealed additional benefits in terms of positive changes across adult learning, behavior, and perspectives; child communication; and child-caregiver relationships.

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28. Morales A, Korsakova E, Mansooralavi N, Ravikumar A, Rivas G, Soliman P, Rodriguez L, McDaniel T, Lund A, Cooper B, Bhaduri A, Lowry WE. Probing DNA damage in Rett syndrome neurons uncovers a role for MECP2 regulation of PARP1. Stem Cell Reports. 2025: 102645.

Methyl-CpG-binding protein 2 (MECP2)/Rett syndrome is characterized by a postnatal loss of neurophysiological function and regression of childhood development. While Rett neurons have been described as showing elevated senescence and P53 activity, here we show that molecular and physiological dysfunction in neurons lacking MECP2 is triggered by elevated DNA damage. Using human induced pluripotent stem cell (hiPSC)-derived isogenic lines, we find that MECP2 directly interacts with members of the DNA repair machinery, including PARP1. Here, we present evidence that MECP2 also regulates PARP1 activity, and restoration of PARP1 activity in MECP2-null neurons can reverse DNA damage, senescence, dendritic branching defects, and metabolic dysfunction. These data from a human disease-in-a-dish model system support the notion that dysfunction in Rett syndrome neurons could be caused by changes in PARP activity.

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29. Øverland E, Andersen PN, Skogli EW, Hauge Å L, Pellicano E. « One must think autism in everything one does »: Clinicians’ Experiences of Supporting Autistic Patients. J Autism Dev Disord. 2025.

PURPOSE: Studies have consistently shown that autistic individuals often find their interactions with healthcare professionals unhelpful, indicating unmet needs. This issue is exacerbated by healthcare professionals’ inadequate knowledge about autism and communication difficulties between healthcare professionals and autistic patients. This qualitative study sought to gain a deeper understanding of clinical encounters between healthcare professionals and autistic patients, from the perspectives of clinicians. METHODS: We conducted five in-depth focus groups with 20 experienced clinicians in Child and Adult Mental Health services in Norway. We used reflexive thematic analysis to analyze the data, using an inductive approach. RESULTS: We found that, overall, clinicians want to be respectful and flexible in their clinical encounters with their autistic patients. We also identified four themes, including that clinicians: 1) are attentive to the varied responses to diagnoses; 2) understand the importance of adapting their communication styles toward the needs of their autistic patients; 3) recognize the need for greater focus on quality of life and autonomy; and 4) acknowledge the significant role that parents play in autistic young people’s lives. CONCLUSION: Although neurodiversity-affirming attitudes amongst clinicians are encouraging, whether they are demonstrated in practice needs further investigation. The findings indicate that support for autistic patients should be more comprehensive and persist for a longer time.

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30. Pearson H. US autism research gets $50-million funding boost – amid row over Tylenol. Nature. 2025.

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31. Pearson H, Thompson B. Audio long read: Autism is on the rise – what’s really behind the increase?. Nature. 2025.

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32. Petropoulos A, Stavropoulou E, Tsigalou C, Bezirtzoglou E. Microbiota Gut-Brain Axis and Autism Spectrum Disorder: Mechanisms and Therapeutic Perspectives. Nutrients. 2025; 17(18).

Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms and gut microbiota imbalances. The microbiota-gut-brain (MGB) axis is a bidirectional communication network linking gut microbes, the GI system, and the central nervous system (CNS). This narrative review explores the role of the MGB axis in ASD pathophysiology, focusing on communication pathways, neurodevelopmental implications, gut microbiota alteration, GI dysfunction, and emerging therapeutics. Methods: A narrative review methodology was employed. We searched major scientific databases including PubMed, Scopus, and Google Scholar for research on MGB axis mechanisms, gut microbiota composition in ASD, dysbiosis, leaky gut, immune activation, GI disorders, and intervention (probiotics, prebiotics, fecal microbiota transplantation (FMT), antibiotics and diet). Key findings from recent human, animal and in vitro studies were synthesized thematically, emphasizing mechanistic insights and therapeutic outcomes. Original references from the initial manuscript draft were retained and supplemented for comprehensiveness and accuracy. Results: The MGB axis involves neuroanatomical, neuroendocrine, immunological, and metabolic pathways that enable microbes to influence brain development and function. Individuals with ASD commonly exhibit gut dysbiosis characterized by reduced microbial diversity (notably lower Bifidobacterium and Firmicutes) and overpresentation of potentially pathogenic taxa (e.g., Clostridia, Desulfovibrio, Enterobacteriaceae). Dysbiosis is associated with increased intestinal permeability (« leaky gut ») and newly activated and altered microbial metabolite profiles, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPSs). Functional gastrointestinal disorders (FGIDs) are prevalent in ASD, linking gut-brain axis dysfunction to behavioral severity. Therapeutically, probiotics and prebiotics can restore eubiosis, fortify the gut barrier, and reduce neuroinflammation, showing modest improvements in GI and behavioral symptoms. FMT and Microbiota Transfer Therapy (MTT) have yielded promising results in open label trials, improving GI function and some ASD behaviors. Antibiotic interventions (e.g., vancomycin) have been found to temporarily alleviate ASD symptoms associated with Clostridiales overgrowth, while nutritional strategies (high-fiber, gluten-free, or ketogenic diets) may modulate the microbiome and influence outcomes. Conclusions: Accumulating evidence implicates the MGB axis in ASD pathogenesis. Gut microbiota dysbiosis and the related GI pathology may exacerbate neurodevelopmental and behavioral symptoms via immune, endocrine and neural routes. Interventions targeting the gut ecosystem, through diet modification, probiotics, symbiotics, or microbiota transplants, offer therapeutic promise. However, heterogeneity in findings underscores the need for rigorous, large-scale studies to clarify causal relationships and evaluate long-term efficacy and safety. Understanding MGB axis mechanisms in ASD could pave the way for novel adjunctive treatments to improve the quality of life for individuals with ASD.

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33. Rezapour M, Bowser J, Richardson C, Gurcan MN. Transcriptional Consequences of MeCP2 Knockdown and Overexpression in Mouse Primary Cortical Neurons. Int J Mol Sci. 2025; 26(18).

Rett syndrome (RTT) and MECP2 duplication syndrome, a subtype of autism spectrum disorder (ASD), are neurodevelopmental disorders caused by MeCP2 loss and gain of function, respectively. While MeCP2 is known to regulate transcription through its interaction with methylated DNA and chromatin-associated factors such as topoisomerase IIβ (TOP2β), the downstream transcriptional consequences of MeCP2 dosage imbalance remain partially characterized. Here, we present a transcriptome-centered analysis of mouse primary cortical neurons subjected to MeCP2 knockdown (KD) or overexpression (OE), which model RTT and ASD-like conditions in parallel. Using a robust computational pipeline integrating generalized linear models with quasi-likelihood F-tests and Magnitude-Altitude Scoring (GLMQL-MAS), we identified differentially expressed genes (DEGs) in KD and OE relative to wild-type (WT) neurons. This study represents a computational analysis of secondary transcriptomic data aimed at nominating candidate genes for future experimental validation. Gene Ontology enrichment revealed both shared and condition-specific biological processes, with KD uniquely affecting neurodevelopmental and stress-response pathways, and OE perturbing extracellular matrix, calcium signaling, and neuroinflammatory processes. To prioritize robust and disease-relevant targets, we applied Cross-MAS and further filtered DEGs by correlation with MeCP2 expression and regulation directional consistency. This yielded 16 high-confidence dosage-sensitive genes that were capable of classifying WT, KD, and OE samples with 100% accuracy using PCA and logistic regression. Among these, RTT-associated candidates such as Plcb1, Gpr161, Mknk2, Rgcc, and Abhd6 were linked to disrupted synaptic signaling and neurogenesis, while ASD-associated genes, including Aim2, Mcm6, Pcdhb9, and Cbs, implicated neuroinflammation and metabolic stress. These findings establish a compact and mechanistically informative set of MeCP2-responsive genes, which enhance our understanding of transcriptional dysregulation in RTT and ASD and nominate molecular markers for future functional validation and therapeutic exploration.

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34. Salem SM, Ismaiel NN, Metwally AM, Ashaat EA, Kobesiy MM. miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder. J Mol Neurosci. 2025; 75(4): 124.

One of the well-studied epigenetic regulators is miRNA (miRNA) which plays critical roles in gene regulation and has been implicated in autism spectrum disorder (ASD) pathology, particularly through their involvement in neuroinflammation and neuronal regulation. MiR-146A and miR-146B are of special interest due to their dysregulation in ASD. Epigenetic modifications, such as promoter methylation, and genetic variations in miRNAs can influence their expression and function, yet their roles in ASD remain unclear. This study aimed to investigate promoter methylation patterns and sequence variations in miR-146A and miR-146B to evaluate their potential contributions to ASD. The study included Egyptian patients with ASD (ages 5-16 years) diagnosed using DSM-V criteria and assessed for severity using the Childhood Autism Rating Scale (CARS). DNA was extracted from peripheral blood samples of 93 autistic patients and 44 age-matched controls. Methylation-specific PCR (MSP) was used to analyze promoter methylation of miR-146A and miR-146B, while Sanger sequencing was employed to detect sequence variations in these genes and their flanking regions. Statistical analyses included independent t-tests, ANOVA, ROC curve, and Pearson correlation. No significant differences in promoter methylation levels of miR-146A and miR-146B were observed between ASD cases and controls or among severity subgroups (P > 0.05). Sequence variation analysis identified no significant differences in the distribution of common SNPs (rs2910164 and rs2224374). However, a novel miR-146A upstream variant (C/A at 5:160,485,254) was discovered in one case with autism. Methylation and common genetic variations in miR-146A and miR-146B are unlikely to play significant roles in ASD in this population. The discovery of a novel upstream variant highlights the potential importance of regulatory regions in miRNA function. Further studies with larger cohorts and functional validation are recommended.

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35. Shi J, Chen M, Zhang Y, Fan X, Wang L, Liao H. Targeting synaptic plasticity and acetylcholine dysregulation in the medial prefrontal cortex: Rosmarinic acid attenuates Autism-like phenotypes in Shank3B(-/-) mice via the CREB/BDNF pathway. Psychopharmacology (Berl). 2025.

RATIONALE: Autism spectrum disorder (ASD) is characterized by cognitive deficits, repetitive behaviors, and social impairments. The SH3 and multiple ankyrin repeat domains protein 3B-deficient (Shank3B(-/-)) mouse model displays ASD-related phenotypes. While rosmarinic acid (RosA) is known for its neuroprotective properties, its role in ASD remains unclear. OBJECTIVE: This study aimed to investigate the therapeutic effects and potential molecular mechanisms of RosA in alleviating behavioral dysfunction in Shank3B(-/-) mice. We assessed core ASD-like behavioral indices, performed bioinformatics predictions, and validated the results through molecular biology experiments. METHODS: Social deficits were evaluated using the three-chamber social test and the male-male social interaction test. Repetitive behaviors were assessed through the self-grooming and marble-burying tests. Cognitive and memory functions were measured using novel object recognition, the Y-maze, and nesting behavior tests. The open field test was employed to evaluate motor functions and exploratory activities. High-throughput RNA sequencing (RNA-seq) was used to identify key genes in the medial prefrontal cortex (mPFC) of the different groups of mice. Neurotransmitter levels of acetylcholine (ACh) and γ-aminobutyric acid (GABA) were analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. Additionally, synaptic function and plasticity in the mPFC were assessed by measuring Postsynaptic Density Protein 95 (PSD95) expression and the activation of the p-CREB/BDNF signaling pathway. RESULTS: RosA significantly improved repetitive behaviors, as well as cognitive and memory abilities, in Shank3B(-/-) mice. It also enhanced motor functions and exploratory activities. However, RosA did not show significant therapeutic effects on social deficits. RNA-seq analysis revealed that RosA notably regulated synaptic proteins. Molecular biology experiments indicated that RosA upregulated PSD95 expression and activated the p-CREB/BDNF signaling pathway in the mPFC, enhancing synaptic plasticity. RosA also increased ACh levels without affecting GABA, indicating a cholinergic mechanism. No significant effects were observed in wild-type (WT) mice, suggesting specificity to ASD-related deficits. CONCLUSION: RosA alleviates cognitive deficits and repetitive behaviors in Shank3B(-/-) mice through CREB/BDNF-mediated synaptic and cholinergic regulation in the mPFC. However, its lack of effect on social deficits suggests distinct mechanisms underlying ASD symptoms. These findings highlight the potential of RosA as a targeted ASD therapy.

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36. Su C, Hu Y, Liu Y, Zhang N, Tan L, Zhang S, Yi A, Xiao Y. Linking connectivity dynamics to symptom severity and cognitive abilities in children with autism spectrum disorder: An fNIRS study. J Neurosci. 2025.

Functional near-infrared spectroscopy (fNIRS) has emerged as a valuable tool for investigating neurobiological markers in children with autism spectrum disorder (ASD). While previous studies have identified abnormal functional connectivity in ASD children compared to typically developing (TD) peers, brain connectivity dynamics and their associations with autism symptoms and cognitive abilities remain underexplored. We analyzed fNIRS data from 44 children (30 boys, 21 ASD/23 TD) aged 2.08-6.67 years while they viewed a silent cartoon. Using sliding window correlation and k-means clustering, we assessed group differences in dynamic connectivity and the correlations with symptom severity and cognitive performance. Our results revealed that children with ASD showed reduced dwell time in a specific brain state and fewer state transitions compared to TD children. These atypical brain state patterns were negatively correlated with autism symptom severity and positively correlated with adaptive behavior and cognitive performance across participants. Mediation analysis revealed that adaptive behavior fully mediated the relationship between brain dynamics and cognitive performance. Furthermore, dynamic connectivity features achieved 74.4% accuracy in distinguishing ASD from TD children. Importantly, the link between brain dynamics and cognitive performance was replicated in an independent TD sample, underscoring the robustness of this finding. Together, these findings highlight altered brain dynamics in young children with ASD and underscore the critical role of adaptive behavior in bridging neural activity and cognitive performance. These insights advance our understanding of neural mechanisms underlying ASD and point to potential pathways for early interventions and clinical applications.Significant statement The brain dynamics and their relationships with symptom severity and cognitive abilities in children with autism spectrum disorder (ASD) remain poorly understood. Using dynamic functional connectivity analysis, our study identified distinct brain state patterns in children with ASD. These patterns were associated with both autism symptom severity and cognitive performance. Importantly, adaptive behavior emerged as a crucial mediator between brain dynamics and cognitive function. Our findings provide novel insights into the neural mechanisms of ASD and highlight the critical role of adaptive behavior in formulating future intervention strategies. By linking specific neural dynamics to adaptive behaviors and cognitive abilities, our study enhances our understanding of ASD neurobiology and has the potential to improve outcomes for affected children.

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37. Sun YH, Tseng SH, Hou WH, Chen HC, Lin CW, Wang YH. Impact of extended reality interventions on core deficits and functional performance among individuals with autism spectrum disorder: A systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2025.

BACKGROUND: Recently, extended reality technologies have been increasingly utilized in therapeutic and educational interventions for individuals with autism spectrum disorder (ASD). This systematic review and meta-analysis evaluated the effectiveness of extended reality interventions in addressing core deficits and enhancing functional performance among individuals with ASD. METHODS: A systematic literature search was conducted across six databases-namely, PubMed, Embase, Cochrane Library, PsycINFO, CINHAL, and ERIC-from their inception to August 29, 2024, with no language restrictions. Studies were included if they (1) examined participants diagnosed with ASD; (2) employed an intervention utilizing virtual reality, augmented reality, or mixed reality; (3) used outcome measures related to social functioning, behavior, emotion, cognition, and anxiety; and (4) were published in a peer-review journal. The standardized mean difference (SMD) was employed as the primary effect size indicator, while heterogeneity was assessed using the I² statistic. Additionally, the quality of the included studies was systematically analyzed. RESULTS: A meta-analysis of 11 randomized controlled and 20 non-randomized trials was conducted using a random-effects model. The extended reality intervention resulted in significant improvements in social skills (SMD: 0.59, p = 0.04), behavior (SMD: 0.61, p = 0.004), emotion recognition ability (SMD: 0.86, p = 0.0005), and cognitive ability (SMD: 0.92, p < 0.00001) among individuals with ASD. CONCLUSION: This study's findings substantiate the effectiveness of extended reality interventions for addressing core deficits and enhancing functional performance among individuals with ASD. Therefore, the utilization of extended reality in therapeutic and educational interventions for individuals with ASD is both feasible and promising.

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38. Tenev A, Markovska-Simoska S, Müller A, Mishkovski I. Entropy and Complexity in QEEG Reveal Visual Processing Signatures in Autism: A Neurofeedback-Oriented and Clinical Differentiation Study. Brain Sci. 2025; 15(9).

(1) Background: Quantitative EEG (QEEG) offers potential for identifying objective neurophysiological biomarkers in psychiatric disorders and guiding neurofeedback interventions. This study examined whether three nonlinear QEEG metrics-Lempel-Ziv Complexity, Tsallis Entropy, and Renyi Entropy-can distinguish children with autism spectrum disorder (ASD) from typically developing (TD) peers, and assessed their relevance for neurofeedback targeting. (2) Methods: EEG recordings from 19 scalp channels were analyzed in children with ASD and TD. The three nonlinear metrics were computed for each channel. Group differences were evaluated statistically, while machine learning classifiers assessed discriminative performance. Dimensionality reduction with t-distributed Stochastic Neighbor Embedding (t-SNE) was applied to visualize clustering. (3) Results: All metrics showed significant group differences across multiple channels. Machine learning classifiers achieved >90% accuracy, demonstrating robust discriminative power. t-SNE revealed distinct ASD and TD clustering, with nonlinear separability in specific channels. Visual processing-related channels were prominent contributors to both classifier predictions and t-SNE cluster boundaries. (4) Conclusions: Nonlinear QEEG metrics, particularly from visual processing regions, differentiate ASD from TD with high accuracy and may serve as objective biomarkers for neurofeedback. Combining complexity and entropy measures with machine learning and visualization techniques offers a relevant framework for ASD diagnosis and personalized intervention planning.

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39. Valencia-Buitrago M, Oliveira-Carvalho RD, Cardoso V, Triviño-Valencia J, Salamanca-Duque LM, Martínez-Díaz V, Zabaleta J, Galeano-Vanegas NF, Naranjo-Galvis CA. Metagenomic Characterization of Gut Microbiota in Children with Autism Spectrum Disorder: Microbial Signatures and Modulation by Anti-Inflammatory Diet and Probiotics. Pharmaceuticals (Basel). 2025; 18(9).

Background: Autism Spectrum Disorder (ASD) is increasingly associated with alterations in gut microbiota, intestinal permeability, and immune dysregulation. However, integrative studies exploring these mechanisms in Latin American populations are lacking. Objective: To characterize gut microbiota profiles in Colombian children with ASD and evaluate the effects of two microbiota-targeted interventions, an anti-inflammatory diet and a probiotic formulation, on microbial diversity and taxonomic composition. Methods: In a two-phase study, shotgun metagenomic sequencing was performed on fecal samples from 23 children with ASD and 7 typically developing (TD) controls. In the second phase, 17 children with ASD were randomized to receive a 12-week intervention (anti-inflammatory diet, probiotics, or no intervention). Alpha diversity indices (Shannon, Pielou, and Chao1) and differential abundance analyses were conducted. Results: Compared to TD children, those with ASD showed a higher Firmicutes/Bacteroidetes ratio and a significantly increased abundance of genera such as Clostridioides, Thomasclavelia, Alistipes, and Coprococcus. The presence of functional gastrointestinal disorders (FGIDs) in ASD patients is associated with reduced microbial richness. POST-intervention, the anti-inflammatory diet group showed that no statistically significant changes in alpha diversity were observed, although a slight upward trend was noted and significant enrichment of six bacterial genera, including Moraxella and Eubacterium. The probiotic group exhibited a significant increase in Romboutsia and a decrease in Lachnospira. Cytokine-microbiota networks in ASD were fragmented and dominated by IFN-γ and MCP-1 hubs, indicating systemic immune activation. Interventions induced functional remodeling: The anti-inflammatory diet increased the number of beneficial genera (Eubacterium, Adlercreutzia) and shifted networks toward positive correlations involving IL-8 and MIP-1β. Probiotics increased Romboutsia, reduced Lachnospira, and restructured networks with regulatory cytokines (SDF-1α, Eotaxin) and SCFA-producing taxa (Blautia, Roseburia). Conclusions: Children with ASD in Colombia displayed distinct microbial profiles characterized by pro-inflammatory taxa and altered richness. Both the anti-inflammatory diet and probiotics produced compositional shifts in the gut microbiota, although global changes in diversity were limited. These findings support the potential of microbiota-targeted nutritional strategies for ASD and underscore the need for precision interventions tailored to specific clinical and microbial phenotypes.

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40. Van Esch N, Boucher TQ, Iarocci G, Scheerer NE. First Impressions Matter: Exploring Children’s Negative Perceptions of Autistic Children. J Autism Dev Disord. 2025.

PURPOSE: Many autistic individuals experience social challenges that may stem from negative perceptions held by their non-autistic peers. This study aimed to examine school-aged children’s first impressions of autistic and non-autistic children based on viewing brief videos. The central research question was whether autistic children are perceived differently in terms of social traits and how these perceptions affect willingness to engage with them. METHODS: Thirty-seven children aged 5-12 years old viewed brief (10 s) videos of both autistic and non-autistic children discussing their interests. Participants then rated each child on social traits (i.e., strange, confident, honest, mean, likeable, smart) and indicated their behavioral intentions (i.e., willingness to live near, sit near, hang out with and talk to) towards the children in the videos. RESULTS: Autistic videos were rated as appearing more awkward, more aggressive, and less likeable compared to non-autistic videos. However, participants reported a similar willingness to interact with both groups. Importantly, these negative perceptions were not associated with the rater child’s age, IQ, sex, autistic traits, or social competence. CONCLUSION: The findings suggest that school-aged children hold biased perceptions of autistic children, independent of their own personal characteristics. This underscores the need for early educational interventions in schools to address stereotypes about and biases against autism. Teaching children about autism could reduce stigma, foster inclusion, and improve social interactions between autistic and non-autistic peers.

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41. van Rooij D, Mou Y, White T, Voortman T, Jansen PW, Buitelaar JK. Prenatal Vitamin D, Multivitamin, and Folic Acid Supplementation and Brain Structure in Children with ADHD and ASD Traits: The Generation R Study. Nutrients. 2025; 17(18).

BACKGROUND/OBJECTIVES: Maternal vitamin supplementation (including folic acid, vitamin D, and multivitamin supplements) during pregnancy may lower the likelihood of neurodevelopmental disorders in offspring. This study examines the associations between maternal vitamin suppletion during pregnancy and morphological patterns in offsprings’ brain structure and traits of Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) in a large population-based study of child development. METHODS: The study cohort included a total of 3937 children (aged 9-11) participating in the Generation R cohort in Rotterdam, the Netherlands. Maternal vitamin D and folateserum levels, multivitamin supplement use, and overall dietary quality (as assessed by the Food Frequency Questionnaire, FFQ) during pregnancy were used as predictors. T1 structural MRI scans were acquired and segmented using Freesurfer to assess brain morphometry. Cortical and subcortical brain volumes of children were separated into four independent components and used as mediators. ADHD and ASD traits, as measured by parent-completed questionnaires (Child Behavior CheckList and Social Responsiveness Scale, respectively) were used as outcome variables. RESULTS: Results show that (1) maternal vitamin D, multivitamin supplementation, and better diet quality were associated with fewer ADHD or ASD traits in the offspring; (2) vitamin D and diet quality were associated with larger-volume childhood brain components; (3) larger-volume brain components were associated with fewer ADHD and ASD traits; (4) part of the association between dietary factors in pregnancy and offspring ADHD and ASD traits was mediated through the brain volumes of the children. CONCLUSIONS: Though all observed effect sizes were small, further population-based research should be performed to further delineate the effects of gestational multivitamin and vitamin D exposure and investigate whether this may be an avenue for preventive interventions.

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42. Wang H, Zhu X, Zhang H, Chen W. Integrating Network Analysis and Machine Learning Identifies Key Autism Spectrum Disorder Genes Linked to Immune Dysregulation and Therapeutic Targets. Genes (Basel). 2025; 16(9).

BACKGROUND: Understanding the genetic mechanisms and identifying potential therapeutic targets are essential for clarifying Autism Spectrum Disorder (ASD) etiology and improving treatments. This study aims to bridge the gap between basic transcriptomic discoveries and clinical applications in ASD research. METHODS: Differentially expressed genes (DEGs) of GSE18123 datase were identified. A protein-protein interaction (PPI) network was constructed. Functional enrichment analysis was performed to link genetic loci to relevant biological pathways. Connectivity Map (CMap) analysis was used to predict potential drugs. Furthermore, immune infiltration correlation analysis explored associations between key genes and immune cell subpopulations. Diagnostic performance of top genes was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The functional enrichment analysis successfully revealed relevant biological processes associated with ASD, while the CMap analysis predicted potential drugs that were consistent with some clinical trial results. Random forest analysis selected ten key feature genes (SHANK3, NLRP3, SERAC1, TUBB2A, MGAT4C, TFAP2A, EVC, GABRE, TRAK1, and GPR161) with the highest importance scores for autism prediction. Immune infiltration analysis showed significant correlations in genes and multiple immune cell types, demonstrating complex pleiotropic associations within the immune microenvironment. ROC curve analysis indicated that most top genes had strong discriminatory power in differentiating ASD from controls, particularly MGAT4C (AUC = 0.730), highlighting its potential as a robust biomarker. CONCLUSIONS: This study effectively bridges the basic transcriptomic discoveries and clinical applications in ASD research. The findings contribute to a better understanding of the etiology of ASD and provide potential therapeutic leads. Future research could focus on validating these potential drugs in clinical studies, as well as further exploring the biological functions of the identified genes to develop more targeted and effective treatments for ASD.

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43. Wang L, Li X, Yuan J, Chen Y. DAGMNet: Dual-Branch Attention-Pruned Graph Neural Network for Multimodal sMRI and fMRI Fusion in Autism Prediction. Biomedicines. 2025; 13(9).

Background: Accurate and early diagnosis of autism spectrum disorder (ASD) is essential for timely intervention. Structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) provide complementary insights into brain structure and function. Most deep learning approaches rely on a single modality, limiting their ability to capture cross-modal relationships. Methods: We propose DAGMNet, a dual-branch attention-pruned graph neural network for ASD prediction that integrates sMRI, fMRI, and phenotypic data. The framework employs modality-specific feature extraction to preserve unique structural and functional characteristics, an attention-based cross-modal fusion module to model inter-modality complementarity, and a phenotype-pruned dynamic graph learning module with adaptive graph construction for personalized diagnosis. Results: Evaluated on the ABIDE-I dataset, DAGMNet achieves an accuracy of 91.59% and an AUC of 96.80%, outperforming several state-of-the-art baselines. To validate the method’s generalizability, we also validate it on ADNI datasets from other degenerative diseases and achieve good results. Conclusions: By effectively fusing multimodal neuroimaging and phenotypic information, DAGMNet enhances cross-modal representation learning and improves diagnostic accuracy. To further assist clinical decision making, we conduct biomarker detection analysis to provide region-level explanations of our model’s decisions.

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44. Wawer J, Chojęta A, Wawer GA, Gładki M, Klotzka A, Kociński B, Urbanowicz T, Kocki J, Grywalska E. The Significance of Serum Immunoglobulin Concentrations in Children with Autism Spectrum Disorders: In Search of Potential Blood Biomarkers. Int J Mol Sci. 2025; 26(18).

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders characterized by a number of dysfunctions in communication, social interactions and repetitive rigid patterns of behavior, interests, and activities. Despite much research, the causes of ASD remain elusive. In addition to genetic and epigenetic etiology, scientists have indicated inflammation, deregulation of cytokines, anti-brain autoantibodies, gut microbiota, and deregulated immunity as mechanisms possibly involved in the development of ASD phenotype. The aim of the study was to analyze the levels of IgA, IgE, and IgM immunoglobulins in the blood serum in patients with ASD to find out whether certain blood parameters are deregulated in that group of patients. The results suggest altered production of the immune cells in ASD patients which may be considered in the assessment of immune functions. Also, PCT% and LYMPH elevated values in patients with ASD might be of clinical relevance, possibly of predictive value for clinical preliminary diagnosis and therapy.

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45. Wnuk-Kłosińska A, Sowińska-Seidler A, Piechota M, Jamsheer A. Novel Biallelic INTS1 Variants May Expand the Phenotypic Spectrum of INTS1-Related Disorders-Case Report and Literature Review. Genes (Basel). 2025; 16(9).

Background/Objectives: Neurodevelopmental disorders (NDDs) are genetically heterogeneous conditions with a complex molecular etiology involving numerous genes. Biallelic pathogenic variants in INTS1 cause a rare autosomal recessive NDD characterized by congenital cataracts, growth retardation, facial dysmorphism, and global developmental delay. To date, the clinical description of this disorder has been based solely on individual case reports, and its phenotypic spectrum remains incompletely defined. Methods: A 9-year-old female proband was evaluated for developmental delay, multiple congenital anomalies, and distinctive craniofacial features. Whole-exome sequencing (WES) was performed, followed by Sanger validation and segregation analysis. Variant pathogenicity was assessed using in silico prediction tools and 3D protein structural modeling. Results: Whole-exome sequencing identified two novel compound heterozygous missense variants in INTS1, c.1145G>A (p.Arg382Gln) and c.1195G>A (p.Gly399Ser), both located in exon 9. Segregation analysis showed that c.1145G>A was inherited from the father and c.1195G>A from the mother, and both variants are extremely rare in population databases. Conclusions: We report a patient carrying novel biallelic INTS1 variants, whose clinical presentation differs from previously reported cases, including those with milder phenotypes characterized by preserved speech development and absence of intellectual disability. This observation broadens the clinical spectrum of INTS1-related disease and underscores its phenotypic heterogeneity.

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46. Woods K, Dunn R, Smith I, Di Basilio D. « I Don’t Think Anyone’s Ever Asked Me About the Two Before »: Making Sense of Co-occurring Autism and BPD in Inpatient Mental Health Settings. J Autism Dev Disord. 2025.

PURPOSE: Autistic individuals and individuals with borderline personality disorder (BPD) are both more likely than the general population to require access to mental health services, specifically inpatient services. Both groups of individuals have reported difficulties when accessing inpatient services including stigma, lack of understanding and lack of adaptations. Recent research has suggested having diagnoses of both autism and BPD is becoming more common and that individuals with both diagnoses may be more at risk of suicidal thoughts and self-harm behaviours. The aim of this study is to understand the experiences of accessing inpatient mental health services for individuals with a diagnosis of autism and BPD. METHODS: Semi-structured interviews were conducted with participants. The data were analysed using reflexive thematic analysis. RESULTS: Seven participants were interviewed. Six themes were developed: (i) Never fully understood, (ii) Intense need for care and connection, (iii) Prisoner or patient? When care and punishment are intertwined, (iv) Necessary evil, (v) System always wins, (vi) Responsible for own care. CONCLUSIONS: Autistic individuals with BPD require personalised care that integrates both their diagnoses into their identities. To provide this, staff on inpatient wards need appropriate support including reflective spaces and clinical supervision. Inpatient systems also need to shift away from prioritising the needs of the system and towards prioritising the needs of the individual, including adaptations for autistic individuals.

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47. Wu C, Li X, Wang H, Liu Z. Altered Gut Microbial Diversity and Depletion of SCFA-Producing Taxa Associated with ASD-like Phenotypes in a Prenatal VPA Rat Model. Int J Mol Sci. 2025; 26(18).

Autism spectrum disorder (ASD) involves complex genetic-environmental interactions. Prenatal valproic acid (VPA) exposure, a known environmental risk factor, induces ASD-like phenotypes in rodents, although the mechanisms linking gut microbiota dysbiosis to neurobehavioral deficits remain unclear. Evidence suggests gut-brain axis dysregulation via altered microbial diversity and reduced short-chain fatty acid (SCFA)-producing taxa contributes to ASD pathogenesis. This study investigated whether prenatal VPA exposure drives ASD-like behaviors through gut dysbiosis and SCFA-producer depletion (e.g., Clostridia, Lachnospiraceae), exploring neuroinflammation and oxidative stress as mechanisms. An ASD rat model was established by maternal VPA injection during specific gestational days. Behavioral tests assessed anxiety, sociability, repetitive behaviors, and cognition. Gut microbiota composition (16S rRNA sequencing), cytokine levels (ELISA), oxidative stress markers (biochemical assays), and microglial activation (Iba1 immunofluorescence) were analyzed. VPA-exposed offspring showed ASD-like behaviors accompanied by neurodevelopmental toxicity, manifesting as social deficits, repetitive grooming, and impaired memory. Concurrently, gut analysis revealed reduced alpha diversity and depleted SCFA-producers (e.g., Clostridia, Lachnospiraceae), alongside increased Bacteroidia and Enterobacteriaceae. Neuroinflammation (elevated IL-1β, IL-6, TNF-α, microglial activation) and oxidative stress (reduced GSH, SOD; elevated MDA, NO) were evident. Multivariate analyses linked dysbiosis to behavioral impairments. Prenatal VPA exposure induces gut microbiota dysbiosis, potentially exacerbating neuroinflammation and oxidative stress to drive ASD-like phenotypes. This establishes a mechanistic link between prenatal insults, gut-brain axis disruption, and neurodevelopmental abnormalities, highlighting microbial modulation and SCFA supplementation as potential ASD therapeutics. Furthermore, integrating behavioral, microbial, and molecular analyses advances understanding of gut-brain interactions in ASD and identifies microbiota-metabolite pathways as targets for neurodevelopmental disorders.

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48. Zhang K, Zhang Y, Chen J, Dai Y, Jin Y. The Influence of Computerized Dynamic Assessment on the Learning Potential of Graphical Analogical Reasoning in Children with Autism: Evidence from Eye-Movement Synchronization. Behav Sci (Basel). 2025; 15(9).

Graphical analogical reasoning ability is crucial for the cognitive development of children with autism spectrum disorder (ASD). However, there are currently no methods available to enhance its analogical reasoning potential. This study aims to explore whether computerized dynamic assessment (CDA) can tap into the potential of children with ASD in graphical analogical reasoning, and simultaneously analyze the influence of the initial abilities of children with autism on their analogical reasoning potential. A total of 71 children with ASD were selected for the study and randomly divided into two groups: (1) the experimental group, namely the computerized dynamic assessment group; (2) the control group, namely the non-computerized dynamic assessment group. Both groups went through three stages: pretest, intervention, and posttest. The research results (including performance, time taken, and eye-tracking analysis) show that compared with non-DA, CDA enables more children to reach medium and high levels of learning potential score. CDA can effectively improve the figural analogical reasoning ability of autistic children in the short term, enhance their attention to learning materials, and boost their answering efficiency. However, this promotion effect is difficult to sustain in the long term. Autistic children with the same initial ability levels show significant differences in learning potential after computerized dynamic assessment because everyone has personalized characteristics. Among children with different initial ability levels, those with lower initial abilities benefit more significantly from dynamic assessment.

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49. Zuo M, Zhang Y, Wang R, Huang D, Yu L, Wang S. Discrimination and Integration of Phonological Features in Children with Autism Spectrum Disorder: An Exploratory Multi-Feature Oddball Protocol. Brain Sci. 2025; 15(9).

Background/Objectives: Children with Autism Spectrum Disorder (ASD) often display heightened sensitivity to simple auditory stimuli, but have difficulty discriminating and integrating multiple phonological features (segmental: consonants and vowels; suprasegmental: lexical tones) at the syllable level, which negatively impacts their communication. This study aims to investigate the neural basis of segmental, suprasegmental and combinatorial speech processing challenges in Mandarin-speaking children with ASD compared with typically developing (TD) peers. Methods: Thirty children with ASD and thirty TD peers will complete a multi-feature oddball paradigm to elicit auditory ERP during passive listening. Stimuli include syllables with single (e.g., vowel only), dual (e.g., vowel + tone), and triple (consonant + vowel + tone) phonological deviations. Neural responses will be analyzed using temporal principal component analysis (t-PCA) to isolate overlapping ERP components (early/late MMN), and representational similarity analysis (RSA) to assess group differences in neural representational structure across feature conditions. Expected Outcomes: We adopt a dual-framework approach to hypothesis generation. First, from a theory-driven perspective, we integrate three complementary models, Enhanced Perceptual Functioning (EPF), Weak Central Coherence (WCC), and the Neural Complexity Hypothesis (NCH), to account for auditory processing in ASD. Specifically, we hypothesize that ASD children will show enhanced or intact neural discriminatory responses to isolated segmental deviations (e.g., vowel), but attenuated or delayed responses to suprasegmental (e.g., tone) and multi-feature deviants, with the most severe disruptions occurring in complex, multi-feature conditions. Second, from an empirically grounded, data-driven perspective, we derive our central hypothesis directly from the mismatch negativity (MMN) literature, which suggests reduced MMN amplitudes (with the exception of vowel deviants) and prolonged latencies accompanied by a diminished left-hemisphere advantage across all speech feature types in ASD, with the most pronounced effects in complex, multi-feature conditions. Significance: By testing alternative hypotheses and predictions, this exploratory study will clarify the extent to which speech processing differences in ASD reflect cognitive biases (local vs. global, per EPF/WCC/NCH) versus speech-specific neurophysiological disruptions. Findings will advance our understanding of the sensory and integrative mechanisms underlying communication difficulties in ASD, particularly in tonal language contexts, and may inform the development of linguistically tailored interventions.

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