1. Aivazidis A, Memi F, Rademaker K, Koko M, Roberts K, Trinh A, Petryszak R, Kleshchevnikov V, Tuck L, Lisgo S, Li T, Makarchuk S, Prete M, Nowakowski TJ, Martin HC, Bayraktar OA. A spatial transcriptomic atlas of autism-associated genes identifies convergence in the developing human thalamus. bioRxiv. 2025.

Autism is a highly heritable neurodevelopmental condition that manifests across a wide phenotypic spectrum. Rare and de novo loss-of-function mutations strongly predispose to autism and co-occurring developmental and intellectual disabilities in over 10% of autistic individuals. Understanding whether these variants converge on specific regional brain circuits or widely alter human brain development is crucial to understanding the etiology of profound autism. To date, transcriptomic atlases have mainly implicated the developing cerebral cortex, yet other brain areas have received relatively little attention. Here, we present a single-cell resolution spatial transcriptomic atlas of 250 autism susceptibility genes during human brain development. Profiling over 10 million cells across the midgestation forebrain, we found convergence of these genes across a small number of regional programs. The developing thalamus showed the most prevalent expression of autism susceptibility genes, followed by germinal zones throughout the brain. Within the thalamus, excitatory neurons showed the most enriched expression, which varied across thalamic nuclei harboring distinct circuits. Across the germinal zones, neural progenitors in the medial ganglionic eminences that generate parvalbumin- and somatostanin-positive interneurons showed highest expression. Our findings reveal the prevalent expression of autism associated genes beyond the developing cerebral cortex and implicate the developing human thalamus as a major hub of autism susceptibility.

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

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

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3. Bacha JD, Zoebi NE, Al-Attrache H. Catalase Gene Variants and Oxidative Stress in Autism Spectrum Disorder: A Northern Lebanon Cohort and Aripiprazole In Vitro Toxicity. Int J Dev Neurosci. 2025; 85(7): e70071.

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition influenced by genetic, epigenetic and environmental factors. Oxidative stress and antioxidant enzyme polymorphisms, particularly catalase (CAT), have been implicated in ASD, but findings remain inconsistent. In parallel, pharmacological interventions such as aripiprazole, which is widely used in ASD, have cellular toxicological profiles that remain incompletely defined. METHODS: A total of 94 participants (39 ASD patients and 55 controls) were genotyped for the CAT polymorphism rs7943316 using tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Genotype distributions were statistically compared using χ(2) and Fisher’s exact tests. In vitro toxicological assays were performed in Saccharomyces cerevisiae wild type (BY4741) and mutant strains deficient in oxidative stress and lipid metabolism genes (CAT1, CPT2, PXA2 and FAA1). Yeast growth was quantified under increasing concentrations of aripiprazole, and IC(50) values were determined. RESULTS: Genotype distribution of rs7943316 showed no significant difference between ASD and control groups (p = 0.866), indicating no association between this CAT polymorphism and ASD risk in this Lebanese cohort. Toxicological profiling revealed that aripiprazole caused dose-dependent growth inhibition. Mutant strains lacking CAT1, CPT2 or PXA2 exhibited significantly reduced IC(50) values compared to wild type (p < 0.05), highlighting oxidative stress detoxification, carnitine-mediated acetyl-CoA transport and peroxisomal fatty acid import as key determinants of drug sensitivity. CONCLUSION: CAT polymorphism rs7943316 is not associated with ASD in this population. However, aripiprazole exerts dose-dependent toxicity strongly modulated by oxidative stress and metabolic pathways. These findings support the integration of genetic and toxicological approaches for understanding ASD and optimizing therapeutic safety.

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4. Batterink L, Liu Y, Westerkamp G, Citarella J, Siekierski P, Voorhees L, Ethridge LE, Smith E, Elmaghraby R, Erickson CA, ElSayed Z, Goel A, Wu SW, Pedapati EV. Aberrant Neural Entrainment to Word-Level Speech Patterns in Fragile X Syndrome: Evidence for a Statistical Learning Deficit. bioRxiv. 2025.

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder, causes significant language and cognitive impairments. Statistical learning refers to the ability to extract patterns from sensory input through mere exposure and plays a central role in language acquisition. Surprisingly, statistical learning in FXS has not been explored. Given that children with FXS typically follow a delayed developmental trajectory for language, we hypothesized that they would show impaired statistical learning. To test this hypothesis, we used an EEG measure of neural entrainment to index statistical learning of hidden trisyllabic words within a continuous speech stream in children with FXS (n = 17) and in typically developing controls (n = 31). Children with FXS showed significantly reduced neural entrainment to words compared to controls, particularly in the superior temporal gyrus and transverse temporal gyrus (primary auditory cortex), providing evidence of statistical learning impairment. Notably, syllable-level entrainment was preserved or even enhanced in FXS, indicating that word-level deficits cannot be attributed to general auditory processing impairments. In addition, while typically developing controls showed an increase in word-level entrainment over the course of learning, children with FXS failed to show a similar increase over time. Taken together, this pattern of results demonstrates that children with FXS can process rapid, lower-order acoustic structure but struggle to integrate these syllables into longer, chunk-like word representations. Overall, these findings suggest that statistical learning is impaired in FXS, and also suggest neural entrainment to statistical structure as a potential therapeutic target.

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5. Bhavna K, Ghosh N, Banerjee R, Roy D. A lightweight, end-to-end explainable, and generalized attention-based graph neural network model trained on high-order spatiotemporal organization of dynamic functional connectivity to classify autistics from typically developing. Netw Neurosci. 2025; 9(4): 1323-51.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social cognition, interaction, communication, restricted behaviors, and sensory abnormalities. The heterogeneity in ASD’s clinical presentation complicates its diagnosis and treatment. Recent technological advancements in graph neural networks (GNNs) have been extensively used to diagnose brain disorders such as ASD, but existing machine learning models often suffer from low accuracy and explainability. In this study, we proposed a novel, explainable, and generalized node-edge connectivity-based graph attention neural network (Ex-NEGAT) model, leveraging edge-centric high-order spatiotemporal organization of dynamic functional connectivity streams between large-scale functional brain networks implicated in autism. Using the Autism Brain Imaging Data Exchange I and II datasets (total samples = 1,500), the model achieved 88% accuracy and an F1-score of 0.89. Additionally, we used meta-connectivity subtypes to identify subgroups within ASD samples using the rough fuzzy c-means algorithm. We also used connectome-based prediction modeling, which revealed critical brain networks contributing to predictions that accurately correlate with Autism Diagnostic Observation Schedule (ADOS) and full intelligent quotient (FIQ) scores. The proposed framework offers a robust approach based on previously unexplored higher order spatiotemporal correlation features of dynamic functional connectivity, which may provide critical insight into ASD heterogeneity and improve diagnostic precision. In this study, we proposed a novel, explainable, and generalized node-edge connectivity-based graph attention neural network model, leveraging edge-centric high-order spatiotemporal organization of dynamic functional connectivity streams between large-scale functional brain networks implicated in autism. The connectome-based prediction modeling reveals critical brain networks contributing to predictions that accurately correlate with ADOS and FIQ scores. The proposed framework offers a robust approach based on previously unexplored higher order spatiotemporal correlation features of dynamic functional connectivity, which may provide critical insight into autism spectrum disorder heterogeneity and improve diagnostic precision. eng.

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6. Carter EW, Escobar MV, Hollinger C, Eshman SR, Mire SS. « It’s So Tough! »: Barriers to Respite Care for Families of Children With Disabilities. Intellect Dev Disabil. 2025; 63(6): 512-23.

Although respite care can have a profound impact on the well-being of families, most parents of children with disabilities struggle to access these scarce services. The purpose of this qualitative study was to map the breadth of barriers families encounter in their pursuit of respite care. We interviewed 31 parents of children and youth with intellectual and developmental disabilities (IDD) about their experiences and the challenges they navigated. Fifteen key barriers emerged in our analyses, highlighting the complexities of this pursuit and the multifaceted issues that can arise for families. We offer recommendations for research and practice aimed at expanding access to this much-needed-but often elusive-family support.

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7. Chen J, Ismail AS, Xie X. Comparative evaluation of play environment design elements in autism schools using AHP and GRA. Sci Rep. 2025.

Autistic children have unique cognitive, sensory, and social needs, and play environments are key to their development, yet existing research lacks systematic quantitative evaluation frameworks. This study fills this gap by evaluating key design elements of play environments in autism schools within the Yangtze River Delta Region through an integrated Analytic Hierarchy Process (AHP) and Grey Relational Analysis (GRA) framework-an innovative methodological attempt in this field. Focusing on developmental outcomes for autistic children, the research systematically prioritizes ten critical design elements across four autism-specific institutions using structured expert evaluations. AHP assigned objective weights to each element, while GRA enabled a comparative assessment of environmental performance based on expert and teacher inputs. Results highlight safety and sensory-friendly design as the most critical factors, whereas personalization and spatial size showed lower significance. The findings advance evidence-based strategies for optimizing autism school play spaces, propose a balanced design framework harmonizing safety, sensory regulation, and social interaction, and provide support for formulating autism-friendly educational environment policies.

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8. Dischler A, Avvaru A, Lopez-Ignacio S, Lau C, Breuss MW, Cerdeño VM, Dashnow H, Dias CM. Long-read sequencing reveals extensive FMR1 somatic mosaicism in Fragile-X associated tremor/ataxia syndrome in human brain. bioRxiv. 2025.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder caused by a CGG repeat expansion in the 5′ untranslated region of the X-linked Fragile X messenger ribonucleoprotein 1 ( FMR1) . Although the CGG repeat tract is known for instability that has been posited to contribute to clinical heterogeneity, the extent of somatic variation in human brain remains unclear, in part due to the technical limitations of sequencing long tandem repeats. Here, we quantified FMR1 somatic variation in post-mortem brain tissue from individuals with FXTAS (n = 6) and Fragile X syndrome (FXS, n = 2) by applying amplification-free, targeted, long-read sequencing. This approach uncovered remarkable somatic mosaicism in repeat size and methylation in FXTAS, including somatic expansions and contractions which were not resolvable with traditional approaches. For example, in FXTAS, we identified somatic expansions to over 6000 base pairs in length as well as contractions to below the pathogenic range. We also identified unexpected patterns of methylation mosaicism on pre and full mutations. On the other hand, we replicated prior findings suggesting differential CGG expansion on the active X-chromosome in XX females. Finally, we examined the above cohort for expansions in 19 additional disease-associated repeat loci. Remarkably, we identified additional expansions in 5 out of 8 affected individuals, in FXN and RFC1 . This work provides new insight into the extensive molecular variation underlying FXTAS in human brain and establishes a framework for studying repeat expansion disorders more broadly, highlighting the potential of long-read sequencing to advance our fundamental understanding of somatic mosaicism of these intractable regions of our genome.

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9. Gigliotti F, Martelli ME, Foglietta S, Balestrini A, Sogos C. Exploring the Association Between Medically Assisted Reproduction and Autism Spectrum Disorder: Clinical Correlations from a Retrospective Cohort. Pediatr Rep. 2025; 17(6).

Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairments in social interaction and communication, as well as by repetitive behaviors, with a rising global prevalence. Concurrently, the use of Assisted Reproductive Technologies (ART) has increased among couples experiencing infertility. This study aimed to compare the frequency of ART-conceived children between those diagnosed with ASD and those with other neurodevelopmental disorders (nASD), and to examine differences in prenatal, perinatal and medical histories of ART- and spontaneously (non-ART)-conceived children within an ASD group. Methods: We retrospectively analyzed data from 507 children with a neurodevelopmental disorders (NDDs) diagnosis, classified into ASD (n = 234) and nASD (n = 273) groups. Subsequent analyses focused on the ASD group, further divided into an ART and non-ART group according to the conception mode. Results: ART-conceived children were more frequent in the ASD group than in the nASD group. Moreover, within ASD, ART was significantly associated with potential risk factors such as twin pregnancy, cesarean delivery, low birth weight and parental age. Logistic Binary Regression confirmed these results, suggesting that ART co-occurs with a cluster of perinatal and familial risk factors. Conclusions: Our results indicate that ART is not an independent causal exposure; however, given the retrospective design and the absence of a general population control group, causal inference cannot be drawn. The observed association with ASD appears to be mediated by perinatal and parental variables. These findings underscore the importance of improving obstetric management and care, and ensuring early developmental monitoring for ART-conceived children.

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10. Goryunov AV, Shushpanova OV, Blinova TE. [Aripiprazole in the treatment of psychiatric disorders in childhood]. Zh Nevrol Psikhiatr Im S S Korsakova. 2025; 125(10. Vyp. 2): 38-47.

For child psychiatry, the priority task is not only the relief of psychopathological symptoms, but also the preservation and restoration of cognitive functioning. Drugs that are active against a wide range of psychopathological disorders, including the productive, negative, affective, and cognitive domains, while having a favorable tolerance profile, will be the most suitable for solving this problem. The unique therapeutic profile of aripiprazole meets all these requirements. The efficacy and tolerability of Aripiprazole in children and adolescents have been demonstrated in many open-label clinical trials, which served as the basis for the drug’s approval by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia, bipolar disorder, and irritability associated with autistic disorder in children and adolescents. Aripiprazole is also included in national clinical guidelines for the treatment of autistic disorders. The high frequency of prescribing aripiprazole in childhood is due not only to its positive effect on negative, cognitive and affective symptoms, but also to its good general tolerance, low probability of developing extrapyramidal symptoms, absence of adverse effects on body weight and metabolic parameters (lipid profile, tissue sensitivity to insulin, etc.).

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11. Goryunov AV, Shushpanova OV, Blinova TE, Golubeva NI. [Cogitum in the treatment of mental disorders in childhood]. Zh Nevrol Psikhiatr Im S S Korsakova. 2025; 125(10. Vyp. 2): 88-95.

The development of many mental disorders, including schizophrenia and autism, is associated with early organic damage to the central nervous system. Moreover, even in severe cases of schizophrenia and autism spectrum disorders, endogenous factors are the main cause of the disease, and organic lesions serve as triggers or aggravating circumstances. The drug Cogitum, a synthetic analog of N-acetylaspartate, is actively used in pediatric neuropsychiatry. This aspartic acid derivative, is critically important for brain development, hormonal regulation, and steroidogenesis. It is present in high concentrations in the brains of embryos and newborns, participating in key metabolic processes. The review analyzes current research on the use of Cognition in various mental disorders – ADHD, delayed speech development, asthenic conditions, autistic and schizophrenic spectrum disorders. According to the results of the studies presented in this article, the drug Cogitum has shown its effectiveness and safety for children. It is concluded that further studies of the therapeutic potential of Cogitum in various diseases are necessary to expand the indications for use.

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12. Hugh ML, Michael OG, Joshi MM, Hernandez AM, Locke JJ. Exploring Factors Across Levels Impacting Educators’ Selection of Evidence-Based Practices for Autistic Students. Implement Res Pract. 2025; 6: 26334895251389976.

Introduction: Front-line implementers report that selecting an evidence-based practice is the most challenging aspect of supporting Autistic students, which may contribute to the long-standing implementation gap. There is a need to understand educators’ (special education teachers’, general education teachers’, and paraeducators’) decision-making and determinants of their evidence-based practice (EBP) selection. Method: This study aimed to identify educators’ decision-making factors, focusing on (a) information sources and (b) factors within the student, intervention, educator, and classroom levels. Eighty-one educators (general education teachers, special education teachers, and paraeducators) participated in semistructured interviews regarding their EBP selection for a specific student they served in inclusive classrooms. Results: General and special education teachers cited EBP sources from their teacher preparation and colleagues with autism expertise, while paraeducators relied on existing classroom practices and guidance from other educators. EBP decision-making frequently revolved around student and intervention characteristics, focusing less on educator, environment, and resource determinants. Educators made individualized EBP decisions for each student, selecting EBPs that served all students. They also shared that their decision-making was most supported through collaboration, despite limited opportunity. Conclusion: The study provides insights into key team members’ EBP selection for Autistic students to aid in the development of implementation supports. Educators’ Choices of Teaching Practices for Autistic Elementary Students Teachers and paraeducators face challenges when deciding what evidence-based practices (EBPs) to use for Autistic children. This decision-making process is crucial and may contribute to the ongoing gap in using these practices effectively. To better understand what educators consider or think about when deciding to use or not use a practice, we interviewed 81 educators (general education teachers, special education teachers, and paraeducators) on why and how they choose practices for Autistic students who they serve in inclusive settings. The study aims to identify the how educators learned about practices (i.e., information source), how they considered factors related to the student, the intervention, the educator, and the classroom environment, and how they worked together to make these decisions. General and special education teachers often mentioned teacher preparation programs, school-based training, and advice from colleagues as their main sources of information. In contrast, paraeducators relied more on existing classroom practices and guidance from other educators. When making decisions about EBPs, educators focused mainly on the characteristics of the student and the intervention, paying less attention to factors related to the educator, the environment, and available resources. They described different ways of collaborating, from team-based decision-making to following directions from others. This study provides insights into the decision-making processes of key team members in using EBPs. These insights can help develop better supports to improve collaboration among educators and enhance the selection of EBPs for use in inclusive settings. eng.

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13. Hughes OE. Gender and Sexual Self-Determination in the Lives of LGBTQ+ Adults With IDD. Intellect Dev Disabil. 2025; 63(6): 485-97.

Adults with intellectual and developmental disabilities (IDD) have the right to gender and sexual self-determination, meaning they should have choice and control in how they express their gender and sexuality. In this inclusive research study, I interviewed 23 LGBTQ+ adults with IDD from the United States to examine their perspectives on barriers and facilitators to gender and sexual self-determination. The participants described how societal attitudes, validation, acceptance, access to information, personal agency, and connections with the LGBTQ+ community could present barriers or facilitators to their gender and sexual self-expression. These perspectives have implications for improving practices and policies to promote the right to gender and sexual self-determination.

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14. İpek Ö Y, Kirboğa T, Babur E, Dursun N, Süer C. Therapeutic timing limitations of postnatal darbepoetin in a valproic acid rat model of Autism Spectrum Disorder. PLoS One. 2025; 20(11): e0337294.

Autism spectrum disorder (ASD) arises from complex genetic and environmental factors that disrupt neural development during early brain maturation. Erythropoietin (EPO) has been studied for its neuroprotective effects and more recently for its potential to influence neurodevelopment in early postnatal ASD models. However, ASD is not typically diagnosed in humans until 2-3 years of age, a stage well beyond early postnatal development. To address this timing gap, we administered darbepoetin alfa, a long-acting EPO analogue, to valproic acid-exposed rats beginning at postnatal day 21 for five consecutive days, and assessed ASD-relevant social and cognitive behaviors. Behavioral assessments using the three-chamber test and Morris Water Maze revealed no significant improvements in ASD-relevant behaviors despite clear systemic activity, as evidenced by substantial hematocrit elevation (~70%). Our findings suggest the therapeutic window for EPO analogues may close before the post-diagnostic period, highlighting a critical translational challenge: interventions effective in early neonatal windows may not retain efficacy at clinically accessible diagnostic stages. The pronounced hematological response further precludes testing whether higher doses could compensate for delayed timing, though non-erythropoietic derivatives may circumvent this limitation in future studies.

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15. Kavanaugh BC, St Pierre DG, Schremp C, Robbins A, Best CR, Jones RN, Sheinkopf SJ, Morrow EM. Later Age of Autism Diagnosis in Children with Multiple Co-Occurring Psychiatric Disorders. medRxiv. 2025.

PURPOSE: In children with autism spectrum disorder (ASD), early diagnosis permits early access to therapeutic interventions which may improve outcomes. Factors affecting the age of diagnosis in ASD are not fully understood. METHODS: Here, two large independent datasets were analyzed to investigate age of autism diagnosis and co-occurring psychiatric conditions, including bipolar disorder, depressive disorder, anxiety disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder. Clinical characteristics examined included demographics, verbal status, intellectual disability, restricted/repetitive behaviors, adaptive behaviors, and psychiatric medication use. RESULTS: Over 50,000 participants with ASD were analyzed from the Rhode Island Consortium for Autism Research and Treatment study (RI-CART; n=823) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) database (n=52,611). In RI-CART, age of diagnosis differed between those with no co-occurring conditions (mean age at diagnosis = 4.3 years), those with one or two co-occurring conditions (7.1 years), and those with three or more co-occurring conditions (8.5 years; p<.001). This pattern was observed in the SPARK database (age of diagnosis 4, 7.1, and 10 years, respectively; p<.001). Controlling for age, sex, and symptom severity, more co-occurring psychiatric conditions was associated with later age of ASD diagnoses in both samples. Depression and ADHD were associated with later ASD diagnoses; OCD and ID were associated with earlier ASD diagnoses. CONCLUSION: These findings indicate that those children with high co-occurring psychiatric conditions, who are ultimately diagnosed with ASD, experience later diagnosis. This group of children may represent a distinct subtype of autism.

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16. Khachadourian V, Anderson M, Arildskov ES, Grove J, Reichenberg A, Sandin S, Schendel D, Hansen SN, Croen LA, Janecka M. Cross-Setting Replication of the Associations Between Maternal Health and Autism. J Am Acad Child Adolesc Psychiatry. 2025.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition with early-life origins. Maternal health conditions during pregnancy have been linked to autism risk, but most studies focus on single populations, limiting generalizability. We examined whether associations previously reported in a Danish registry-based study hold in a U.S. METHOD: We analyzed electronic health records of children born between 2010 and 2017 at Kaiser Permanente Northern California (KPNC) and their mothers. Maternal diagnoses were classified as chronic or non-chronic, and associations with ASD in the child were assessed using Cox models, adjusting for sociodemographic factors, healthcare utilization, and comorbid maternal diagnoses. Methods were aligned with the Danish study for comparability. RESULTS: Among 224,353 children in the KPNC cohort, 5,448 (2.4%) were diagnosed with autism. Of the 42 maternal diagnoses significantly associated with autism in Denmark, 38 were evaluable in KPNC, and 18 remained statistically significant after adjustment. Most associations had point estimates consistent with the Danish study, particularly psychiatric and cardiometabolic conditions. CONCLUSION: Despite demographic and healthcare differences, 35 of the 38 associations found in the Danish study replicated qualitatively (direction of effect) in the U.S. cohort, suggesting robust cross-setting relevance. Further research is needed to explore underlying mechanisms and effect modifiers.

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17. Kim T, Lee J, Lee J, Jo H, Oh Y, Kim YJ, Seo J. Sensory abnormalities in autism spectrum disorder and their in vitro modeling. Transl Psychiatry. 2025.

Autism Spectrum Disorder (ASD) is characterized by deficits in social interaction, alongside abnormal sensory reactivity that often manifests as avoidance or repetitive behaviors. This review proposes that these core features may stem from somatosensory system dysfunction responsible for processing sensory information driven by an underlying excitatory-inhibitory (E/I) imbalance, a common finding in ASD models, which could drive such sensory impairments and ultimately contribute to the core social and behavioral deficits. We explore how recent advancements in hiPSC-derived assembloid models, which integrate multiple components of the human somatosensory pathway, provide a powerful platform to investigate these mechanisms. Crucially, this review not only highlights the promise of these models but also provides a critical evaluation of their inherent limitations, including cellular immaturity and the absence of key non-neuronal components. By examining the ongoing strategies to overcome these challenges, such as advanced co-culture systems, xenotransplantation, and bioengineering, this review offers a comprehensive outlook on the future of assembloid technology in elucidating ASD pathophysiology and developing novel therapeutic strategies.

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18. Li C, Burke MM, Arnold CK. Correlates of Individual and Systemic Advocacy Activities Among Siblings of Autistic Individuals. Intellect Dev Disabil. 2025; 63(6): 498-511.

Extensive research has focused on parent advocacy, but the advocacy efforts of siblings of autistic individuals remain less studied. This study aims to identify the correlates of individual and systemic advocacy among siblings of autistic individuals. Using a national survey, 256 adult siblings of autistic individuals indicated their advocacy activities. Descriptive statistics and hierarchical regressions were used for analyses. Results indicated that, although siblings often engaged in both individual and systemic advocacy, they present as distinct constructs with varying correlates. Older siblings who engaged in future planning and/or were knowledgeable about disability policy were more likely to conduct individual advocacy. Systemic advocacy was greater among siblings more connected to the disability community and had reciprocal exchanges of tangible support.

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19. Li R, Dybvik H, Feng D, Eng C, Lee CH, Bartholomay KL, Zhang Y, Lightbody AA, Reiss AL. Atypical Inter-Brain Synchrony and Social Communication Deficits in Girls with Fragile X Syndrome: Evidence from Functional Near-infrared Spectroscopy Hyperscanning. Res Sq. 2025.

Background : Fragile X syndrome (FXS), a leading genetic cause of intellectual disability and autism, is characterized by marked social communication deficits, yet the neural underpinnings of these challenges remain poorly understood. Methods : We employed a functional near-infrared spectroscopy(fNIRS) hyperscanning technique to investigate inter-brain synchrony (IBS) during naturalistic mother-child interactions in girls with FXS (n = 33), compared to age- and verbal IQ-matched controls (n=18)and typically developing (TD) peers (n=12). Dyads engaged in a cooperative tangram task and a free-talk conversation, while fNIRS measured neural activity across prefrontal, temporal, and parietal regions. Results : During a tangram task, the FXS dyads showed distinct IBS patterns, including significantly enhanced IBS in the frontopolar area and reduced IBS in left Broca’s area and dorsolateral prefrontal cortex. In the conversation, FXS dyads showed significantly reduced IBS in the frontal eye field and superior temporal gyrus but enhanced IBS in the right supramarginal gyrus (SMG), a region linked to phonological processing. Linguistically, children with FXS demonstrated significantly lower lexical richness and syntactic complexity compared to their peers. Stronger IBS in the right SMG correlated with better verbal performance ( r = 0.267~0.401, p < 0.05) and higher autism severity ( r = 0.276, p = 0.035). Conclusions : By integrating neural and linguistic metrics, our study pioneers an effective framework for FXS social dysfunction, underscoring IBS as a potential biomarker for FXS and informing targeted interventions leveraging dyadic synchrony to enhance communication outcomes.

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20. Liu S, Li J, Gu H, Wang S, Zhang Y. MTIF-GNN: A Multi-Modal Topology and Integrated Focused Network for ASD Diagnosis. IEEE J Biomed Health Inform. 2025; Pp.

The diagnosis of autism spectrum disorder (ASD) has been a longstanding focus in clinical and neuroscience research, particularly with the growing use of multi-site functional MRI (fMRI) data. However, most existing methods often suffer from limitations such as inadequate multi-modal data fusion and insufficient mining of implicit features. To address these challenges, an end-to-end multi-modal topology-integrated graph neural network (MTIF-GNN) is proposed for multi-site ASD diagnosis. MTIF-GNN constructs two complementary population graphs to fully extract and integrate both explicit and implicit features, aiming to achieve more accurate diagnostic results. To further enhance network performance, an adaptive topology update (ATU) module is designed to dynamically adjust and optimize the graph structure within MTIF-GNN, enabling more effective capture of latent relationships among nodes and global topological patterns. Finally, this study achieves deep integration of explicit and implicit features through joint learning optimization of the graph neural network, and obtains the ASD diagnosis results using a multi-layer perceptron. Experimental results demonstrate that the proposed method outperforms existing approaches and also achieves excellent performance in diagnosing major depressive disorder (MDD), indicating its broad applicability across various psychiatric disorders and providing effective support for cross-disorder brain function research. The code is available at https://github.com/cvmdsp/MTIF-GNN.

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21. Lun MP, Ngo TT, Tilton I, Dandekar R, Pekar M, Thurm A, Bartley CM, Wilson MR, Pleasure SJ. Exploratory autoantibody profiling in autism spectrum disorder. medRxiv. 2025.

There is growing evidence that immune dysfunction interacts with genetic predisposition to increase vulnerability to autism spectrum disorders (ASD). However, few studies have extensively profiled the autoantibody repertoire from children with ASD. Here, we utilized unbiased approaches to identify the antigenic targets of autoantibodies from cerebrospinal fluid (CSF) and blood collected from children with ASD compared to typically developing controls. In a cohort of children with ASD, we identified 6 of 61 participants (9.8%) harbored anti-neural autoantibodies in their CSF with distinct immunoreactivity patterns by tissue-based immunofluorescence screening on murine brain sections. In one participant, two CSF samples collected 2.3 years apart showed persistent anti-neural immunofluorescence. Phage display immunoprecipitation sequencing (PhIP-seq) and immunoprecipitation mass spectrometry (IP-MS) were utilized to screen for the antigenic targets of these CSF immunoreactivities, which revealed that each of these 6 cases have unique autoreactivities in their CSF as well as their peripheral blood. Our screening techniques identified several candidate autoantigens that have strong genetic associations with ASD, including ANK2/3, BCL11A, CHD3/8, NRXN1/2, RUNX1T1, and ZNF292. Broadly, these candidate autoantigens participate in several pathways that may contribute to ASD, including synaptic connectivity, neuronal scaffolding, and transcriptional regulation. While the autoantibody specificities remain to be validated through orthogonal assays, these data demonstrate the potential for parallel unbiased screens to identify autoantibodies with relevance to ASD.

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22. Lyon KA, Paumier A, Kandikonda A, Melendez A, Allen NJ. Astrocyte SEMA3C reduction improves Rett Syndrome phenotypes. bioRxiv. 2025.

During typical neurodevelopment, astrocytes secrete proteins that support neuronal connectivity. This process is disrupted in Rett Syndrome (RTT), a regressive neurodevelopmental disorder characterized by motor, sensory, and cognitive impairments. While astrocytes typically promote neuron outgrowth, co-culture of RTT astrocytes with wildtype neurons inhibits their outgrowth, implicating secreted astrocyte factors in RTT pathology. However, the specific factors and their contributions to RTT deficits remain poorly defined. To address this, we focused on the class 3 semaphorin SEMA3C, which shows increased astrocyte secretion in RTT and other neurodevelopmental disorders. Using astrocyte and neuron cell culture, we find that SEMA3C is inhibitory to dendrite outgrowth via PLXND1 and NRP2 receptors in cortical neurons. Genetic reduction of astrocyte SEMA3C in female RTT model mice enhances dendritic arborization and normalizes synaptic activity. Behaviorally, astrocyte SEMA3C reduction normalizes visual acuity and motor behavior, which are established clinical features in RTT. Together, these findings identify astrocyte SEMA3C as a contributor to RTT pathology and highlight the SEMA3C-NRP2- PLXND1 signaling pathway as a potential therapeutic target in disordered neurodevelopment.

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23. Martín Echave M, Schnack HG, Díaz-Caneja CM, Pina-Camacho L, Janssen N, Gordaliza PM, Kho KH, Buimer EEL, van Haren NEM, Cahn W, Kahn RS, Hulshoff Pol HE, Arango C, Janssen J. Individualized cortical thickness asymmetry in autism spectrum disorder and schizophrenia. Mol Psychiatry. 2025.

Cortical thickness asymmetry has been proposed as a latent biomarker for autism spectrum disorder (ASD) and schizophrenia (SZ). However, the degree of abnormal asymmetry at the individual level in ASD and SZ remains unclear. To investigate this, we employed a normative modeling approach. Normative ranges for the whole brain and regional (160 cortical parcels) cortical thickness asymmetry index (AI) were established using a training set of healthy subjects (n = 4904, 45.15% male, age range: 6-95 years), controlling for age, sex, image quality, and scanner. We calculated z-scores to quantify individual deviations from the normative median in a test set consisting of healthy controls (HC(test), n = 526, 40% male), participants with ASD (n = 135, 83% male), and SZ (n = 287, 81% male). Regional deviance was assessed by counting the number of individuals with significant deviations below (infra-normal, z-score ≤ -1.96) or above (supra-normal, z-score ≥ 1.96) the normative median in each parcel. We also evaluated individual deviance by counting the number of regions with significant deviations for each participant. A multivariate approach was employed to determine whether regional deviance could separate the three groups. There were no differences for deviance of whole brain AI between any of the groups. Distributions of individual deviances overlapped across all 160 regions, with one superior temporal region in which SZ individuals showed a higher proportion of supra-normal AI values compared to HC(test) (HC(test) = 1.14%, SZ = 5.92%, χ(2) = 15.45, P(FDR) < 0.05, ω = 0.14). The SZ group had a higher average number of regions with significant deviations than HC(test) (infra-normal: z = 4.21, p < 0.01; supra-normal: z = 4.33, p < 0.01) but this group difference had limited predictive diagnostic accuracy at the individual level (Area Under the Curve≅60%). The multivariate analysis showed no association between regional deviance and diagnosis. Results were consistent when using a different parcellation, alternative asymmetry calculations, analysis restricted to males, and after controlling for handedness and IQ. Normative modelling revealed little to no evidence of atypical individualized cortical thickness asymmetry in ASD and SZ. The results of this study challenge the utility of cortical thickness asymmetry as a biomarker for ASD and SZ.

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24. Merchie A, Ranty Z, Wardak C, Aguillon-Hernandez N, Bonnet-Brilhault F, Houy-Durand E, Aucouturier JJ, Gomot M. Vocal smile is recognized but not embodied in autistic adults. iScience. 2025; 28(11): 113858.

Autism spectrum disorder (ASD) is frequently characterized by atypical responses to emotional prosody and a lack of response to social smiles. This study examined whether autistic adults show motor resonance to vocal smiles, as reflected in facial muscle activity, when listening to emotional vocal cues. Facial electromyography was recorded while autistic and neurotypical adults listened to sentences spoken with smiling or neutral prosody and judged their emotional content. Both groups accurately recognized smiling prosody, indicating intact perceptual abilities in autism. However, only neurotypical participants showed enhanced zygomaticus activation in response to smiling voices, whereas autistic participants did not modulate facial muscle activity despite correct recognition. This dissociation between identification and motor reactivity suggests that autistic individuals can accurately recognize vocal emotions, but these are not embodied. These findings provide insights into the mechanisms that shape social engagement in ASD and may inform therapeutic approaches targeting emotional embodiment.

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25. Nicklas P, Cruz L, Tirelli C, Bojanek E, De Sanctis P, Freedman E, Molholm S, Foxe J. A symphony of functioning: Assessing the interplay of cognition, movement, and visual processing in adolescents on the autism spectrum using mobile brain-body imaging (MoBI). Res Sq. 2025.

Background Autism Spectrum Disorder (ASD) is characterized by differences across multiple functional domains: cognitive, sensory, motor, etc. There is a need to understand how concurrent demands in different domains can impact performances in one another, as the simultaneous processing and execution of tasks from different domains is how most normal daily tasks and activities are completed. Differences in integration are thought to underly many characters of ASD, and therefore understanding how these domains interact in typically and neurodivergently developing populations is vital for identifying more nuanced and precise markers for supporting diagnosis and treatment decisions. Methods We used Mobile Brain-Body Imaging (MoBI) to simultaneously record 64 channel electroencephalography (EEG), motion-tracking, and response inhibition task performance in adolescents (ages 13-23, mean 16.96 years) with (typical developing, TD) and without ASD. We designed experimental conditions that either did or did not include a motor demand (standing or treadmill walking), sensory demand (static field or optical flow), and cognitive demand (completing task or not) to investigate single, dual, and tri-modal impacts on ERPs, gait kinematics, and task accuracy and speed. Results The TD group was significantly more accurate when walking. The ASD group did not increase task accuracy despite making similar adjustments response speed when going from standing to walking. Optic flow did not impact task accuracy or response speed for either group. Similarly, walking impacted ERP amplitudes and latencies, but the addition of flow did not further these impacts. The ASD group’s neural activity showed differences that were similar in direction, but weaker in magnitude to the addition of more demands (walking and flow), compared to the TD group. Conclusions There is a complex interplay between motor, cognitive, and sensory functions and those we provide evidence here that cross-domain integration of these in adolescents is different in ASD than those who are typically developing, wherein similar adjustments in the groups leads to an increase in accuracy for the TD group but not for the ASD group. Future research should further investigate these relationships with multi-modal methods like MoBI.

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26. Ömercioğlu E, Özçelik E, Akpınar F, Özdereli Z, Öztürk E, Acar B, Çelik P. Autoinflammatory periodic fever syndromes in preschoolers: neurodevelopmental, behavioral, and maternal psychosocial outcomes. Eur J Pediatr. 2025; 184(12): 783.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are the most common pediatric autoinflammatory syndromes, yet their developmental and psychosocial impacts during early childhood remain poorly understood. This cross-sectional study compared developmental and behavioral outcomes, parental mental health, and perceived child vulnerability in preschool-aged children diagnosed with PFAPA syndrome or FMF versus healthy controls. A total of 158 children aged 18-71 months (79 patients, 79 controls of similar age and sex) were recruited from a tertiary pediatric hospital in Turkiye. Development was evaluated using the Ages and Stages Questionnaire and Bayley Scales of Infant and Toddler Development, Third Edition. Behavioral functioning was assessed using the Child Behavior Checklist, while maternal depression, anxiety, and perception of child vulnerability were measured via the Patient Health Questionnaire-9, Beck Anxiety Inventory, and Child Vulnerability Scale. Children with periodic fever syndromes had significantly higher rates of developmental delay (p < 0.05) and lower cognitive, language, and motor scores than healthy peers (all p < 0.05). They also exhibited elevated internalizing and externalizing symptoms. Mothers of affected children reported higher perceptions of child vulnerability. Multivariable logistic regression identified male sex (OR 2.71, 95% CI 1.08-6.85), patient group status (OR 2.65, 95% CI 1.12-6.23), lack of preschool attendance (OR 6.58, 95% CI 2.26-19.19), and lower shared reading frequency (OR 0.76, 95% CI 0.65-0.89) as independent predictors of developmental delay. Among clinical factors, attack frequency was positively associated with internalizing problems. CONCLUSION: Preschool children with PFAPA syndrome and FMF may be at increased risk for early developmental and behavioral difficulties. These findings support the need for routine screening and integrated care approaches that address both child development and caregiver-relate d factors. WHAT IS KNOWN: • PFAPA syndrome and FMF are the most common childhood periodic fever syndromes associated with stress and reduced quality of life in both children and their families. • Although inflammation and psychosocial stress are known to affect early development, their impact in these syndromes remains largely unexplored. WHAT IS NEW: • Preschool children with PFAPA syndrome and FMF are at increased risk for developmental and behavioral difficulties, along with elevated maternal perceptions of child vulnerability. • This is the first study to systematically evaluate early developmental and psychosocial outcomes in these syndromes, identifying clinical and caregiving factors associated with increased risk.

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27. Paštar M, Milanović I, Maksimović S, Đoković S, Fetahović E, Veselinović S, Subotić M. Impact of Severity of Autism on Auditory Behaviour and Receptive Vocabulary in Autism Spectrum Disorder. Percept Mot Skills. 2025: 315125251401272.

Auditory processing deficits are common in children and adults who are diagnosed with autism spectrum disorder (ASD). An intuitive yet underexplored hypothesis is that deficits in auditory processing may manifest in auditory sensory behaviours. As a result of irregularities in the domain of auditory processing, deficits in speech and language processing may occur, and studies show that receptive vocabulary deficits are also often present. This study aimed to examine the differences in auditory behaviour and receptive vocabulary between children with lower and higher degrees of severity of autism. The sample included 30 children aged from three years and five months to six years and 11 months. The GARS-3 was used to determine the severity of autism, the Auditory Processing subscale (APS) from the Sensory Profile and the Questionnaire on Auditory Behavior for Children with Autism Spectrum Disorder (QAB-ASD) (constructed for this study) were used to assess auditory behaviour, and the Peabody Picture Vocabulary Test (PPVT) was used to assess receptive vocabulary. The obtained results indicate that children with a higher degree of severity of autism are more prone to exhibiting atypical auditory behaviour. At the same time, no differences in receptive vocabulary development were found between groups. The correlation between receptive vocabulary and auditory behaviour measured by the APS was not found, but it was with the score on the QAB-ASD. The results suggest the impact of the severity of autism on the manifestation of auditory behaviour but not on the receptive vocabulary development in children with ASD.

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28. Pelle M, Fiori Nastro F, Maimone C, Malara S, Di Lazzaro V, Di Lorenzo G, Ribolsi M. Autism in Adulthood: Psychiatric Comorbidity in High-Functioning Autistic Adults in an Outpatient Clinical Population. NeuroSci. 2025; 6(4).

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition. Diagnosing ASD in adults, especially in milder forms, remains challenging due to camouflaging strategies, adaptive behaviors, and frequent psychiatric comorbidities. Despite increased awareness, there is a critical need to improve recognition and tailored interventions for adults with ASD. This study aims to examine the prevalence of psychiatric comorbidities among individuals diagnosed with ASD. METHODS: This retrospective cross-sectional study examined 64 adults diagnosed with ASD (n = 29 females, 45.3%; age: range, 18-57 years; mean ± SD, 30.9 ± 8.92), who accessed two university hospital outpatient units in Rome between September 2023 and January 2025. All participants were assessed using the Autism Diagnostic Observation Schedule, Second Edition-Module 4 (ADOS-2). Psychiatric comorbidities were evaluated using clinical assessments and the Mini-International Neuropsychiatric Interview (M.I.N.I.) Plus. RESULTS: All patients received an ASD diagnosis without intellectual disability. Forty-four (68.8%) presented with at least one psychiatric comorbidity, most commonly depressive (25.0%) and anxiety disorders (9.4%). Over half of the participants (57.4%) reported at least mild depressive symptoms, and 42.6% exhibited moderate to severe depressive levels. CONCLUSIONS: High rates of psychiatric comorbidities, particularly mood and anxiety disorders, were observed, underscoring the importance of comprehensive, multidisciplinary assessment and individualized interventions. Further research using larger samples and rigorous methodologies is warranted to better characterize the ASD phenotype in adults and guide targeted therapeutic strategies.

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29. Rivard M, Boulé M, Morin M, Abouzeid N, Chatenoud C, Morin D, Mello C, Gore N, Bradshaw J, Hastings R. Early positive approaches to support for family carers of young children with developmental disabilities: adaptation and piloting in Quebec public services. Front Rehabil Sci. 2025; 6: 1627502.

BACKGROUND: This paper presents the participative research undertaken to adapt and pilot the Early Positive Approaches to Support (E-PAtS) program, originally developed and evaluated in English for use in the United-Kingdom, for implementation within Québec’s public health and social services. E-PAtS supports family carers of young children with developmental disabilities by promoting their well-being and adjustment early in their services trajectory. METHOD: The program was translated into French and iteratively adapted based on feedback from six pilot cohorts conducted across four diverse clinical settings: a rural service center, an urban center, a specialized pediatric hospital, and a diagnostic clinic. These sites were selected to ensure demographic and geographic representativity of Québec’s population, and participating families also reflected a range of backgrounds. The adaptation process was grounded in community-based participatory research principles, actively involving parents, practitioners, managers, and researchers. Changes to the program’s content and delivery were made according to partner recommendations. Evaluation focused on social validity, effectiveness, feasibility, and fidelity of implementation. RESULTS: Participating parents completed questionnaires and interviews, reporting improved well-being and greater confidence in self-care, indicating the program’s relevance and positive impact. Fidelity of implementation was assessed using the E-PAtS fidelity checklist, and feasibility was evaluated through session attendance logs. Both indicators were considered strong, despite the challenges posed by the COVID-19 pandemic. CONCLUSION: Findings support the adapted E-PAtS program’s suitability for Québec’s public services, with further refinements recommended for broader dissemination. This study highlights the value of participatory approaches in adapting evidence-based interventions across cultural and service delivery contexts.

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30. Shi D, Guan J, Wang G, Wu S, Zhuang C, Mao Y, Jia Y, Zhao N, Yan G, Wu R. Mapping Resting-State Brain Functional Specialization to Neurotransmitter Profiles in Autism Spectrum Disorder. CNS Neurosci Ther. 2025; 31(11): e70666.

BACKGROUND: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder. However, its diagnosis and effective treatment present challenges. Understanding neurotransmitter impairments may offer new perspectives into the mechanisms underlying ASD and the potential therapeutic targets for this condition. This study aimed to investigate the spatial associations of ASD-related brain activity patterns and multiple specific neurotransmitter distributions to identify abnormal neurotransmitter alterations in patients with ASD, and to assess how these spatial associations relate to clinical features. METHODS: We included 44 patients with ASD and 132 typically developing controls (TDCs) and compared the regional homogeneity (ReHo) differences between the two groups. Associations between the spatial patterns of ReHo alterations and specific neurotransmitter receptor/transporter densities in patients with ASD were evaluated, and the correlations of these associations with the clinical characteristics were analyzed. RESULTS: In comparison with TDCs, patients with ASD exhibited specific brain activity abnormalities in the visuomotor network, cerebro-cerebellar circuits, angular gyrus, and limbic areas. These atypical brain activity patterns were significantly co-localized with the serotonergic, glutamatergic, GABAergic, dopaminergic, noradrenergic, cholinergic, and cannabinoid neurotransmitter systems in patients with ASD, and the results showed good reproducibility between different neurotransmitter maps. Additionally, the awareness score in the Social Responsiveness Scale (ρ = -0.475, p = 0.009) and the social score in the Autism Diagnostic Observation Schedule (ρ = -0.415, p = 0.049) exhibited negative correlations with the strength of ReHo co-localization of serotonin 5-hydroxytryptamine receptor subtype 2a. CONCLUSIONS: This is the first systematic analysis of multiple neurotransmitter systems to show abnormalities in these systems in patients with ASD. These results will enhance the existing understanding of the mechanisms underlying ASD and may provide the foundation for identifying therapeutic targets.

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31. Shogren KA, Linnenkamp B, Townsend R, Edwards B, Rentschler L, Taconet A, Stelter C, Henley R, Bright K, Hildebrandt L, Dean E, Loyless R, Swindler S. Advancing Inclusive Research in Intellectual and Developmental Disabilities: Building Community and Supports for Participation. Intellect Dev Disabil. 2025; 63(6): 457-71.

People with intellectual and developmental disabilities are often excluded from equitable inclusion in the development and execution of research. Despite increased advocacy for inclusive research over the last decade, the widespread use of such practices remains limited. There is a need for systemic change to foster the inclusion of people with intellectual and developmental disabilities in planning, conducting, and disseminating research. This paper describes actions taken by a research group to make system changes to empower and support people with intellectual and developmental disabilities to learn about and engage in research. It highlights ongoing work that is needed and possible ways to advance systemic change.

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32. Silvan A, Di Martino A, Milham MP, Parra LC, Madsen J. Overlap and Differences of Autism and ADHD: Digital Phenotyping of Movement and Communication During Development. bioRxiv. 2025.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) often co-occur, which complicates diagnosis across development. Here, we test whether automatic analysis of naturalistic video can disentangle shared from distinct behavioral signatures of the two disorders. We analyzed videos of 2,341 youths (ages 5-22) from a community sample while they described an emotive short film. Multivariate models revealed that language deficits previously attributed to ADHD were largely explained by age. Difficulties in understanding and recalling a social narrative, sometimes attributed to ADHD, were uniquely predicted by ASD. Increased motor activity was a specific marker of the hyperactive-impulsive domain of ADHD. Conversely, ASD showed structurally intact language but significant impairments in narrative ability and perspective-taking, coupled with a unique vocal profile of higher pitch, intensity, and altered voice quality. These findings suggest that despite substantial comorbidity, ADHD and ASD exhibit separable behavioral profiles that can be measured objectively at scale.

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33. Vanneau T, Brittenham C, Darrell M, Foxe JJ, Molholm S. Neural oscillatory dynamics reveal altered top-down and integrative mechanisms during face processing in autistic children and unaffected siblings of autistic children. bioRxiv. 2025.

Face processing is fundamental to social communication and has been a major focus of autism research. While event-related potential (ERPs) studies of face processing have produced mixed results, little work has examined neuro-oscillatory dynamics, which may better capture the integrity of underlying networks. To address this gap, EEG was recorded from children aged 8-13 across three groups: autistic ( n = 50), non-autistic ( n = 38) and siblings of autistic children ( n = 26), during a visual oddball task. In a blocked design, participants viewed faces and objects, presented upright and inverted (non-targets), to assess the face inversion effect (the FIE; a larger or earlier N170 to inverted than upright faces), and responded to infrequent shadow versions (targets). Analyses using permutation statistics and linear mixed models focused on non-target stimuli, quantifying face-related ERPs (P1, N170) and oscillatory activity associated with sensory and attentional processing (theta, alpha, gamma). Across groups, faces elicited earlier P1 and larger N170 amplitudes than objects, and showed a FIE. Furthermore, the rightward lateralization of the FIE was reduced for autistic participants. Analyses in the frequency domain revealed greater induced theta for inverted versus upright stimuli and for faces versus objects, revealing face specific effects, and stronger theta for inverted faces for the autistic and sibling groups, suggesting greater cognitive effort in processing these social stimuli. Gamma-band inter-trial phase coherence exhibited face selectivity only in the non-autistic group, pointing to differences in early network synchronization in autistic children relative to their non-autistic peers, whereas alpha event-related desynchronization did not vary by group or category. Altogether, these findings support altered neural synchronization/efficiency for autistic participants and siblings of autistic children, that is specific to face stimuli and seen despite largely typical sensory driven encoding. These data suggest that neural oscillatory assays are more sensitive to face processing differences in autism than broadband ERPs and that these oscillatory assays may be endophenotypic.

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34. Wang X, Zhu RX, Du XG, Song HJ. Applying Target Trial Emulation to Evaluate Acupuncture Combined with Rehabilitation for Autism Spectrum Disorder in Children: A Retrospective Single-Center Real-World Protocol. Neuropsychiatr Dis Treat. 2025; 21: 2513-23.

BACKGROUND: Target trial emulation (TTE) has recently emerged as an innovative methodological framework for deriving causal inference from real-world data. Its use in complementary and integrative medicine, however, remains limited. This protocol applies TTE to evaluate the effectiveness of acupuncture combined with rehabilitation in children with ASD, aiming to generate rigorous real-world evidence and bridge the current evidence gap. METHODS: This retrospective TTE study will utilize anonymized data from the ASD registry of Xi’an TCM Hospital of Encephalopathy affiliated to Shaanxi University of Chinese Medicine. Children aged 2-12 years diagnosed with ASD according to DSM-5 criteria will be included. The intervention group will receive rehabilitation therapy plus acupuncture, while the control group will receive standard rehabilitation therapy alone. A total of approximately 250-300 participants will be included, ensuring at least 180 matched cases after propensity score matching. Statistical analyses will include paired t-tests, multivariable regression, and correlation analyses to estimate treatment effects and control for confounding. The TTE defines a clear time-zero (treatment initiation), prespecified censoring and crossover rules, and a causal estimand focusing on the average treatment effect among the treated (ATT). Balance diagnostics and sensitivity analyses will be performed to assess robustness. ANTICIPATED RESULTS: This study is designed to evaluate whether acupuncture combined with rehabilitation leads to greater improvements in ATEC and ABC scores compared with rehabilitation alone. Exploratory neuroimaging analyses will be conducted to investigate potential mechanisms underlying treatment effects. CONCLUSION: This protocol aims to evaluate the effectiveness of acupuncture combined with rehabilitation for children with ASD using a target trial emulation framework applied to real-world data. The study is designed to estimate the causal effect (ATT) while addressing confounding and missing-data issues, and its findings-whether positive or null-will inform future RCT design and the evidence-based integration of acupuncture in neurodevelopmental care. CLINICAL TRIAL NUMBER: Not applicable.

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35. Wei S, Sun Y, Liu G, Peng P. Using Story-Based Thinking Maps to Enhance Metaphor Comprehension Skills in Children With Autism Spectrum Disorder. J Autism Dev Disord. 2025.

PURPOSE: Metaphor comprehension is a critical yet challenging skill for children with Autism Spectrum Disorder (ASD), particularly in understanding psychological related metaphors. This study aims to address this gap by employing story-based thinking maps intervention to enhance comprehension of both physical and psychological related metaphors in children with ASD. METHOD: Three children with ASD (aged 5-8) participated in this study. A concurrent multiple-probe design across two behaviors (physical and psychological related metaphors) and three participants was used, with baseline, intervention, follow-up, and generalization phases. Intervention involved identifying metaphor elements, shared features, and meanings. RESULTS: The results indicated that all participants demonstrated low accuracy during the baseline phase but exhibited similar patterns of improvement during the intervention phase and achieved 100% accuracy. High accuracy rates were maintained during the follow-up and generalization phases. CONCLUSION: The findings suggest that the story-based thinking maps intervention is effective in enhancing metaphor comprehension skills in children with ASD. This study provides valuable insights for designing interventions targeting metaphor comprehension in this population.

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36. Weiss K, Vermudez SAD, Freitas G, Dogra S, Meadows MJ, Gogliotti RG, Niswender CM. Reciprocal regulation of the H (3) histamine receptor in Rett syndrome and MECP2 Duplication syndrome: implications for therapeutic development. bioRxiv. 2025.

Rett syndrome (RTT) and MECP2 Duplication syndrome (MDS) are disorders caused by reciprocal decreases and increases, respectively, in expression of the methyl reader protein, Methyl CpG Binding Protein 2 (MeCP2). MeCP2 is a transcriptional regulator that induces changes in the expression of thousands of genes. We previously performed an mRNA expression profiling study of the temporal cortex region from a cohort of autopsy samples from patients diagnosed with RTT and corresponding age, postmortem interval, and sex-matched controls. These studies identified a significant reduction in the expression of the histamine H (3) receptor ( HRH3 ) in RTT patients compared to controls. In the current manuscript, we expand this H (3) receptor profiling to additional RTT patient brain samples representing distinct disease mutations and confirm significantly reduced levels of H (3) receptor expression in the majority of patients compared to controls. Using mouse models of RTT and MDS, we observed reciprocal changes in H (3) receptor expression across various brain areas, with Hrh3 expression being reduced in RTT model animals and increased in a mouse model of MDS. We then tested the hypothesis that phenotypes in these mouse models would be sensitive to an H (3) receptor agonist and antagonist, respectively. This point is particularly salient for MDS, as there are no approved treatments available; encouragingly, however, the H (3) antagonist/inverse agonist pitolisant (Wakix®) has recently been approved for the treatment of narcolepsy, and we sought here to determine if there was potential to repurpose pitolisant for MDS. We evaluated both a small molecule agonist of the H (3) receptor, ( R )-α-methylhistamine (RAMH), and pitolisant in RTT and MDS models, respectively, to determine impacts on phenotypes in these disease models. Our results show that RAMH significantly impacted an anxiety phenotype in mice modeling RTT ( Mecp (Null/+) ), but pitolisant had no effect on the behaviors examined here in MDS animals ( MECP2 (Tg1) ).

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37. Xu C, Zhang C, Zhou T. A Cross-Lagged Panel Analysis of Basic Psychological Needs Satisfaction and Depressive Symptoms in Parents of Autistic Children: The Mediating Role of Parenting Stress. J Autism Dev Disord. 2025.

PURPOSE: Parents of children with autism spectrum disorder (ASD) face elevated risks of depressive symptoms, which may impair their daily functioning and hinder effective caregiving. Grounded in self-determination theory and conservation of resources theory, this study examined the bidirectional relationship between basic psychological needs (autonomy, competence, relatedness) satisfaction and depressive symptoms, as well as the potential mediating effect of parenting stress in this relationship. METHODS: Using a two-wave cross-lagged design, we assessed 178 Chinese parents of autistic children at baseline and at the three-month follow-up. The participants completed questionnaires on basic psychological needs satisfaction, depressive symptoms, and parenting stress at two waves of survey. RESULTS: The results supported the reciprocal relationship between autonomy need satisfaction and depressive symptoms, as well as the predictive effect of depressive symptoms on subsequent competence/relatedness need satisfaction. The findings also established parenting stress as a bidirectional mediator: it not only mediated the negative effects of depressive symptoms on the three psychological needs satisfaction, but also served as a mechanism through which autonomy need satisfaction buffers against mental health decline. CONCLUSION: These findings highlight the necessity of developing interventions that enhance autonomy support and mitigate parental stress to improve the well-being of parents of autistic children.

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38. Yuan G, Suresh V, Wigdor E, Hao Y, Leonard R, Steyert M, Griffiths M, Evans C, Rohani N, Weiss J, Lassen FH, Schafer N, Dong S, Palmer DS, Sanders SJ, Nowakowski TJ. Disruption of Cell-Type-Specific Molecular Programs of Medium Spiny Neurons in Autism. bioRxiv. 2025.

Autism spectrum disorders (ASD) are highly heritable neurodevelopmental conditions with major contributions from rare genetic variants. Most studies have focused on cortical mechanisms; even growing evidence implicates subcortical circuits in ASD etiology. To systematically map developmental and molecular alterations beyond the cortex, we profiled lineage relationships across five brain regions in an ASD mouse model. Most prominent changes emerged in the striatum, a hub for learning and motor control. Furthermore, we performed single-nucleus multiomic profiling of human putamen from ASD and neurotypical donors revealed cell-type-specific transcriptomic and regulatory alterations. Differential expression converged on synaptic and energy metabolic dysfunctions in D1 striosome medium spiny neurons (MSNs), coupled with astrocytic remodeling of synaptic support. Gene regulatory network analysis identified EGR3 and EGR1 as key transcriptional regulators of ASD-associated programs of D1 MSNs. Together, these results establish the striatum as a central node of ASD convergence and provide a multiomic resource for dissecting its subcortical mechanisms.

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39. Zhang Y, Liu Y. The evolving landscape: A bibliometric and visual analysis of language interventions research for children with ASD. Res Dev Disabil. 2025; 167: 105169.

PURPOSE: This study conducts a multi-database bibliometric analysis to map the intellectual landscape of language intervention research for children with ASD from 2001 to 2024, seeking to identify foundational and trending topics, map collaborative networks, and trace thematic evolution, thereby offering data-driven guidance for setting research priorities, fostering international cooperation, and informing clinical practice translation. METHODS: We systematically searched Web of Science Core Collection, EBSCOhost, and PubMed. After deduplication and screening, 2720 publications were retained for bibliometric analysis using CiteSpace. Co-citation analysis, time-zone map, burst detection, and network visualization identified research clusters and temporal evolution trajectories. RESULTS: Publications exhibited three distinct growth phases: initial exploration (2001-2012), accelerated expansion (2013-2017), and exponential growth (2018-2024). Ten major research clusters comprising 573 nodes demonstrated high structural validity (mean silhouette=0.835, modularity Q=0.812). Augmentative and Alternative Communication (AAC) exhibited the highest structural importance (burst=17.34, sigma=17.15), while computational methods, particularly machine learning (323 citations), showed rapid growth despite peripheral network positions (centrality=0.09), indicating they are emerging yet not central to the mainstream discourse. The United States dominated collaborative networks (betweenness=0.68, 57 connections), with emerging contributions from China, UK, and Canada. CONCLUSION: The temporal analysis reveals that the field has successfully navigated multiple paradigm expansions, evolving from initial behavioral approaches to encompass technological and neurobiological perspectives. Five emerging frontiers warrant strategic investment: computational-clinical integration, telehealth implementation science, AI-enhanced AAC systems, neurobiological phenotyping, and community-based early detection. Future research should prioritize implementation science, foster interdisciplinary collaboration, and embed participatory principles.

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40. Zoromba MA, Alenezi A, El-Monshed AH, Loutfy A, Ali AM, Alkubati SA, El-Gazar HE. Effect of Cognitive-Behavioural Strategies on Self-Efficacy, Sense of Coherence and Psychological Ownership Among Nurses Caring for Children With Autism Spectrum Disorder: A Randomised Control Trial. J Psychiatr Ment Health Nurs. 2025.

BACKGROUND: Nurses caring for children with autism spectrum disorder (ASD) encounter unique challenges that can affect their psychological well-being and professional efficacy. Cognitive-Behavioural Strategies (CBS) are a promising approach to bolster the psychological resources of these nurses. OBJECTIVES: This study sought to evaluate the effects of a structured CBS intervention on self-efficacy, sense of coherence (SOC) and psychological ownership among nurses caring for children with ASD. METHODS: This open-label, two-arm, parallel, randomised controlled trial was conducted from December 2024. A total of 131 registered nurses caring for children with ASD were randomly allocated to an intervention group (n = 65) or a control group (n = 66). The intervention group received a 6-week CBS programme. Outcomes were measured using the General Self-Efficacy Scale, SOC Scale and Psychological Ownership Questionnaire at baseline and post-intervention. RESULTS: After the intervention, the intervention group demonstrated significant improvements compared to the control group in self-efficacy (t = 2.506, p < 0.05), SOC (t = 3.936, p < 0.001) and psychological ownership (t = 2.110, p < 0.05). Within-group analyses indicated significant pre-post improvements in the intervention group across all measures, with large effect sizes for SOC and self-efficacy, and a moderate effect size for psychological ownership. CONCLUSIONS: The CBS intervention significantly improved self-efficacy, SOC and psychological ownership among nurses caring for children with ASD. These findings highlight CBS as a valuable strategy for supporting nurses in specialised care settings, with potential benefits for both nurse well-being and patient care quality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06929858.

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