1. Correction: Effects of improved creative play interventions on social communication, behavioral, and cognitive function in children with autism spectrum disorder: a randomized controlled trial. Front Public Health;2026;14:1856928.

[This corrects the article DOI: 10.3389/fpubh.2026.1768848.].

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2. Avraham R, Ya’akobov LL, Kondelis N, Cohen O. Determinants of Direct Support Professionals’ Mealtime Experiences in an Israeli Long-Term Care Facility for Residents with Intellectual and Developmental Disabilities. Nutrients;2026 (Apr 28);18(9)

Background: Malnutrition is a universal challenge in long-term care, significantly affecting vulnerable populations. Residents with Intellectual Developmental Disability (IDD) rely heavily on Direct Support Professionals (DSPs) for assisted feeding. Understanding DSP’s mealtime experiences is essential for improving nutritional care and well-being. Objective: To examine multilevel factors associated with DSPs’ mealtime experiences. Methods: This exploratory cross-sectional case study used a survey administrated to DSPs working in a long-term residential setting. Statistical analyses examined the associations between multilevel factors and DSP’s positive and negative mealtime experiences. Results: The sample included 46 DSP’s (98% women) from a single facility in Israel. Although DSPs reported high levels of positive feelings and satisfaction with their daily work efficacy, negative feelings were significantly associated with some organizational, environmental and resident-related factors. Negative feelings were higher among DSPs caring for residents who use wheelchairs compared to those working with residents who do not use wheelchairs (t = -2.99, p < 0.01). Negative feelings were negatively associated with institutional support (r = -0.49, p < 0.001), and perceived accessibility and adaptability of the environment (r = -0.46, p = 0.001), and showed a more modest association with communication with residents (r = -0.38, p = 0.01). DSPs' seniority, education level, and prior feeding-related training were not significantly associated with mealtime experience. Conclusions: The findings highlight that negative mealtime experiences among DSPs are associated with organizational, environmental, and resident-related factors, rather than with individual DSP's characteristics. Policy and practical adjustments to address mealtime experiences for residents with IDD are suggested.

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3. Bortoletto R, Fanelli G, Colizzi M. Drug development in autism spectrum disorder: genetic heterogeneity, failed trials, and the case for stratified pharmacotherapy. Int Clin Psychopharmacol;2026 (Apr 10)

Despite three decades of clinical trials, no pharmacological treatment has shown consistent efficacy for the core features of autism spectrum disorder (ASD), and regulatory approvals remain limited to risperidone and aripiprazole for severe irritability. This limited efficacy likely reflects a mismatch between underlying biology and broad trial designs. ASD is a clinically defined neurodevelopmental condition with marked etiologic heterogeneity, shaped by highly polygenic liability and a long tail of rare, often de novo, high-impact variants. Genomic studies implicate synaptic signaling, chromatin regulation, and excitatory-inhibitory processes, but this partial biological convergence does not support a single therapeutic target across the diagnostic spectrum. Debate over environmental risk factors, including prenatal acetaminophen exposure, also shows how weak causal inference can distort research priorities. We propose three priorities for ASD pharmacotherapy: genetically stratified mechanism-linked interventions, pharmacogenomics-informed symptomatic prescribing, and trials using validated or biomarker-informed endpoints that capture outcomes regarded as meaningful by autistic people.

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4. Bradley CA, Ko SY, Tian M, Ralph LT, D’Abate L, Lee J, Liu T, Wang J, Tidball P, Mendes M, Fan X, Howe JL, Alexandrova R, Pellecchia G, Casallo G, Paton T, Wybenga-Groot LE, Engchuan W, Thiruvahindrapuram B, Trost B, de Rijke J, Kadia A, Jin F, Salazar NB, Diaz-Mejia JJ, MacDonald JR, Deneault E, Ross PJ, Ellis J, Shum C, Georgiou J, Rennie O, Reuter MS, Hoang N, Sarikaya E, Selvanayagam T, Amini AE, Rutherford A, Rivera-Alfaro N, Marshall CR, Scala M, Runke CK, Kearney HM, Christodoulou J, Francis DI, Chung BHY, Pluciniczak J, Iaboni A, Wigby KM, Nordahl CW, Amaral DG, Hudson ML, Sjaarda CP, Guerin A, Elsabbagh M, Landa R, Mital S, Lesurf R, Jain A, Wilson MD, Ellegood J, Lerch JP, Lee LJ, Frey BJ, Salter MW, Vorstman JAS, Anagnostou E, Frankland PW, Collingridge GL, Scherer SW. An X-linked long non-coding RNA, PTCHD1-AS, and the core features of autism. Nature;2026 (May 13)

There are around 100 genes or copy-number variations used in genetic testing for autism spectrum disorder (ASD)(1,2). The established genes are protein coding, and the associated phenotypes usually extend beyond sociobehavioural traits seen in autism, including cognitive/medical complexities and attention deficit hyperactivity disorder (ADHD)(3,4). We examined whole-genome sequencing data in cases of ASD (9,349) and controls (8,332) and identify 27 male individuals with ASD with X-chromosome microdeletions that implicate the long non-coding RNA PTCHD1-AS as an ASD-susceptibility gene (odds ratio = 2.56, P = 0.01). Two Ptchd1-as-knockout mouse models, which were created by disrupting/deleting the evolutionarily conserved exon 3, show ASD-like features in male mice, including increased repetitive behaviours and impaired social behaviour and communication without cognitive comorbidities or ADHD-like behaviours. Hippocampus-dependent synaptic function, complex learning and locomotor activity are unaffected in knockout mice. Native nuclear-enriched mouse Ptchd1-as showed sustained expression from postnatal day 7 onwards in the dorsal striatum, a predominantly GABAergic brain region that is implicated in ASD(5). Multi-omics analysis revealed transcriptomic alterations in striatal oligodendrocytes, astrocytes and neurons impacting myelination and synaptic plasticity. Disrupting Ptchd1-as led to reductions in conventional protein kinase C (cPKC) isoforms, altered SRC and GSK-3α/β phosphorylation and enhanced striatal synaptic plasticity (long-term potentiation and long-term depression). Together, these findings implicate striatal molecular and circuit-level dysregulation through PTCHD1-AS in ASD aetiology.

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5. Burrows CA, Rothenberg WA, Garcia D, Peskin A, Jimenez-Muñoz M, Davis E, Jent JF, Parladé MV. Change Trajectories During Parent-Child Interaction Therapy for Autistic Children and Their Caregivers. Autism Res;2026 (May 13):e70260.

Disruptive behaviors (non-compliance, aggression) are common in autistic children. Parent-Child Interaction Therapy (PCIT) is a caregiver-mediated intervention utilizing in vivo caregiver coaching that reduces disruptive behaviors and has been shown to be effective for young autistic children. This study sought to identify child and caregiver factors that relate to session-level progress among autistic children and their caregivers. Participants included 98 autistic children aged 2-8 years (91% male) who received PCIT in a university-affiliated clinic. Session-level change was examined using iterative multilevel modeling to examine change in child disruptive behaviors, as measured on the Eyberg Child Behavior Inventory (ECBI), caregiver positive attending skills (Do-skills), and caregiver negative statements (Avoid-skills). Optimal fitting trajectories revealed quadratic change in ECBI scores, Do-skills, and Avoid-skills. The effectiveness of PCIT did not differ based on participants’ level of autistic traits or caregiver demographics. Improvements in child disruptive behavior were associated with child adaptability and parenting stress pre-treatment; higher adaptability and lower stress were related to faster declines in child disruptive behavior. Caregivers exhibited slower rates of change in Do-skills when they had lower rates of homework completion, and when their child had lower social responsiveness, and challenges with adaptability and externalizing problems. These findings may help clinicians tailor what factors to emphasize and monitor over the course of PCIT. Parent–Child Interaction Therapy (PCIT) is a therapy that helps caregivers manage challenging behaviors in young children by teaching and coaching them in real time. PCIT works well for autistic children who also show a lot of disruptive behavior, like meltdowns and aggression. However, it is still unclear which factors might influence how well the therapy works for each child. In our study, we found that PCIT was helpful in reducing disruptive behaviors for autistic children across a wide range of cognitive abilities and support needs. However, caregivers who reported higher levels of stress and whose children initially showed more behavior problems and greater difficulty adjusting to change generally made slower progress in learning new skills. These findings could help therapists better support families by focusing more on certain areas during treatment. eng

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6. Chahrour MH. Illuminating hidden genetic architecture in autism. Cell Genom;2026 (May 13);6(5):101248.

Structural and repeat variation relevant to autism has remained largely inaccessible to short-read sequencing. Using long-read genome sequencing, a recent study reveals previously hidden variants at scale, quantifies their contribution to autism risk, and links them to gene regulatory disruption in neurodevelopment, expanding the mutational and mechanistic landscape of autism.

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7. Di X, Xu T, Castellanos FX, Biswal BB. Unique Amygdala Signatures and Shared Prefrontal Deficits in Autism: Mapping Social Heterogeneity via Naturalistic functional Magnetic Resonance Imaging. bioRxiv;2026 (Feb 27)

BACKGROUND: Naturalistic fMRI provides an ecologically valid window into social brain function, yet binary diagnostic labels may obscure neural signatures linked to the continuous spectrum of social deficits. We investigated whether social brain alterations in autism spectrum disorder (ASD) follow a categorical, dimensional, or « dual-track » architecture. METHODS: We analyzed fMRI data from 428 youth (262 ASD, 166 typically developing; ages 5-22) watching two films: The Present and Despicable Me . Using Principal Component Analysis (PCA) to quantify primary (PC1) and secondary (PC2) synchronization, we employed variance partitioning to disentangle the contributions of categorical diagnosis from continuous symptom severity (Social Responsiveness Scale-2, SRS-2). RESULTS: During The Present , reduced synchronization was widespread. In social-motivational hubs (medial prefrontal cortex, caudate), reductions were largely explained by variance shared between diagnosis and SRS-2 scores. In contrast, the left amygdala exhibited a unique dimensional association with SRS-2 scores independent of categorical diagnosis. Secondary response patterns (PC2), reflecting complex temporal integration, revealed further unique dimensional effects in the cuneus. Notably, these signatures were stimulus-dependent, manifesting during the emotionally complex narrative of The Present but not during the slapstick-oriented Despicable Me . CONCLUSIONS: While core social-motivational hubs reflect overlapping diagnostic and dimensional deficits, the amygdala and secondary visual patterns provide distinct, dimension-specific signatures of social impairment. This variance partitioning approach supports a Research Domain Criteria (RDoC) framework, highlighting the necessity of integrating dimensional assessments and narrative complexity to characterize the neural architecture of autism.

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8. Dickerson AE, Kim YJ. The Effectiveness of the Vision Coach(TM) Interactive Light Board on Improving Processing Speed Reaction Time in Autistic Individuals. Occup Ther Health Care;2026 (Apr 22):1-15.

The aim of this study was to evaluate if the Vision Coach(TM) interactive light board improves processing speed reaction time among autistic individuals and if it contributes to improvement in driving performance. Fifty-seven participants with autism received individual intervention one to two times a day over five days using the Vision Coach. Using a paired pre-posttest design, results showed that participants took statistically significant less time to complete each speed trial (p < .001, r = 0.28-0.32) and missed statistically significant fewer number of targets at post-test (p < .001, r = 0.35 and 0.46, respectively) than pretest. Lastly, there were significant, positive relationships between the changes in the number of targets missed and in the time taken to tap the correct targets for the trials in Speeds 2 and 3 (p < .001). Since decreased processing speed is commonly observed among individuals with autism, this study offers evidence to support Vision Coach as an occupational therapy intervention that improves functional performance. In addition, results from improved processing speed reaction time on driving performance is discussed.

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9. Doan HT, Phan NTD, Ho HT, Nguyen LTT, Do KN, Nguyen OTP, Trinh NB. Micronutrient status and dietary patterns among children with autism in Central Vietnam: A cross-sectional baseline survey to inform targeted intervention. PLOS Glob Public Health;2026;6(5):e0006385.

Children with autism spectrum disorder (ASD) in low- and middle-income countries may face multiple forms of malnutrition, but data to guide targeted nutrition interventions are limited. We conducted a cross-sectional baseline survey to inform a micronutrient-focused intervention in 48 children aged 2-9 years diagnosed with ASD, recruited from five intervention centers in Central Vietnam. Caregivers completed a 24-hour dietary recall and a one-month food frequency questionnaire. Anthropometric measurements were collected and converted to World Health Organization z-scores. Fasting blood samples were analyzed for hemoglobin, serum ferritin, and serum zinc concentrations. Non-parametric tests and bootstrap confidence intervals were used to compare preschool-aged children (<5 years) with those 5-9 years. Undernutrition was identified in 16.7% (underweight) and 20.8% (stunting), while 6.3% of participants were overweight or obese. Zinc deficiency affected 45.8% of children, low ferritin was found in 16.7%, and anemia in 10.4%. Two concurrent micronutrient deficiencies were present in 16.7%. The median energy intake met 84.6% of national recommendations. Dietary fiber intake was universally inadequate, and most children consumed less than the recommended levels of iodine (97.0%), zinc (64.6%), vitamin C (64.6%), and calcium (56.3%). Older children were significantly more likely to have inadequate calcium intake than younger ones (73.9% versus 40.0%). Dietary patterns were dominated by cereal-based foods, with infrequent intake of legumes, vegetables, dairy, and animal-source foods. These findings reveal a triple burden of undernutrition, micronutrient deficiencies, and emerging overnutrition among children with ASD. The results underscore the urgent need for early nutritional screening and dietary improvement strategies. These baseline data offer critical evidence for designing context-appropriate nutrition interventions in similar low-resource settings.

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10. Elkady NK, Ibrahim DG, Moawad AM, Elmahdy SM, Kamel MH, Amin OR, Elsebaie EH, El Tabei D, Gamal REA, Ahmed HH, Moawad EMI, Hassan RIA, Abdelgawad, II. Assessment of differences in urinary heavy metal concentrations and environmental factors between children with autism spectrum disorder and neurotypical controls. Drug Chem Toxicol;2026 (May 13):1-9.

Heavy metals are associated with autism spectrum disorder (ASD), interfering with neurodevelopment. This study assessed differences in urinary heavy metal concentrations and environmental risk factors between children with ASD and neurotypical controls. A hospital-based case-control study, including 25 ASD patients and 25 age- and sex-matched neurotypical controls aged 5-14 years at the Psychiatry Clinic of Cairo University’s Kasr Al Ainy Hospital, was conducted between September and December 2024. ASD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria, and symptom severity was evaluated using the Childhood Autism Rating Scale, Second Edition. Morning urine samples were collected and analyzed for lead (Pb), mercury (Hg), arsenic (As), and copper (Cu) via inductively coupled plasma optical emission spectroscopy with concentrations standardized to creatinine levels. Guardians completed a questionnaire addressing sociodemographic characteristics and environmental, prenatal, and postnatal exposures. Children with ASD had significantly higher rates of prenatal complications (p = 0.0002) and postnatal complications (p < 0.0001), as did those with prenatal pesticide exposure (p = 0.0006). Aluminum pan usage was more common among children with ASD (p < 0.0001). The urinary levels of As (p = 0.011) and Hg (p = 0.021) were significantly higher in the ASD group, whereas those of Pb and Cu were not significantly different (p > 0.05). Secondhand smoke exposure was the strongest predictor of ASD status (OR = 10.79, p = 0.034). Arsenic and mercury exposure, together with environmental risk factors, may contribute to ASD pathogenesis and highlight the importance of environmental risk assessment in pediatric populations.

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11. Fujita K, Zhu H, Tsuji C, Kawamura A, Nishiyama M, Higashida H, Yokoyama S. Perineuronal nets in cerebellar nuclei neurons orchestrate social behaviour via regulation of neuronal activity in circuits innervated by the cerebellum. Transl Psychiatry;2026 (May 13);16(1)

Certain types of neurons in the central nervous system are wrapped in extracellular matrix protein complexes named perineuronal nets (PNNs). While it is known that PNNs regulate neuronal activity by modulating synaptic plasticity, their pathophysiological role in psychiatric disorders has not been sufficiently clarified. Here, we demonstrate that the expression of PNNs in autism-spectrum-disorder (ASD)-associated mice, valproic acid-injected mice and chromodomain helicase DNA-binding protein 8 (Chd8) gene haploinsufficient mice was decreased in cerebellar nuclei neurons. The pharmacological disruption of PNNs by the enzyme chondroitinase ABC (ChABC) injection into the deep cerebellar nuclei was associated with an impairment of social interaction compared with sham-operated mice. In the large glutamatergic neurons, neuronal activity was increased during social behavior which was revealed by intracellular calcium dynamics and phosphorylation of cAMP responsive element-binding protein 1 (CREB1). The transcriptional factor aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), which regulates neuronal activity, was increased in ChABC-injected mice and ASD-associated mice under the basal condition without any neuronal activity-dependent stimulation of gene expression. Moreover, the evaluation of neuronal activity by the increase of c-Fos in distal regions, including the red nucleus and ventromedial thalamic nuclei, revealed that ChABC injection into the deep cerebellar nuclei negatively affected the c-Fos induction after the social interaction test. The reduction of ARNT2 by injection of adeno-associated virus (AAV) carried shRNA-ARNT2 into the deep cerebellar nuclei, together with ChABC, rescued the impairment of social interaction and restored the induction of c-Fos expression in distal regions compared with scrambled-shRNA-injected mice. Therefore, the present results may imply a functional role of PNNs in the regulation of neuronal activity in the circuits innervated by the cerebellum that orchestrate social behaviour.

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12. Kanno M, Yoshida Y, Fujihashi M, Takahashi N, Numazawa T, Mizuno Y. Dimensional Structure of BERT-Estimated Emotion Representations in Adolescents With Autism Spectrum Disorder: An Exploratory Analysis of Clinical Narratives. Cureus;2026 (Apr);18(4):e106830.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by impairments in emotion recognition and regulation. While natural language processing (NLP) offers a systematic approach to estimating emotions from clinical narratives, the latent dimensional structure of these estimated emotions in ASD remains insufficiently characterized using methodologically rigorous frameworks. OBJECTIVE: This exploratory study aimed to characterize the dimensional structure of model-estimated emotions in adolescents with ASD using a fine-tuned Japanese BERT model, while explicitly accounting for domain shift and compositional data constraints. METHODS: A Japanese BERT model (tohoku-nlp/bert-large-japanese-v2) was fine-tuned on the WRIME dataset (social media posts). The model was applied to 1,239 clinical sessions from 14 adolescents with ASD to generate eight-dimensional emotion probability vectors. To address the compositional nature of softmax outputs and the non-independence of repeated sessions, we performed a centered log-ratio (CLR) transformation followed by within-patient centering. Principal component analysis (PCA), with patient-level bootstrapping, was conducted to identify robust dimensions. In-domain validation was performed using 150 manually annotated clinical snippets. RESULTS: The model achieved 81.3% accuracy on the out-of-domain test set, though in-domain validation revealed performance variability across emotion categories (e.g., higher reliability for sadness than for trust). PCA identified two primary dimensions: PC1 (57.8% variance), characterized by a dominant sadness-driven internalizing axis, and PC2 (14.2% variance), representing a contrast between anticipation and aversive emotions (disgust/anger). These dimensions remained stable across bootstrap resampling. CONCLUSIONS: This study demonstrates that transformer-based NLP, when combined with rigorous compositional data analysis, can elucidate latent emotional structures within clinical narratives. However, these patterns reflect a model-mediated representation space influenced by clinical documentation practices and domain-specific model characteristics. While providing a novel quantitative framework for psychiatric NLP, our findings emphasize the necessity of in-domain validation and cautious clinical interpretation.

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13. Lidstone DE. Disparities in Physical Activity and Sport Participation Among Transition-Age Youth With Autism and Intellectual Disability. Autism Res;2026 (May 13):e70277.

Physical activity is critical for health, yet many adolescents do not engage in regular activity. Youth with autism spectrum disorder (ASD) and intellectual disability (ID) may be at heightened risk due to motor, sensory, and social barriers, but less is known about complete disengagement. Using nationally representative data from the 2021-2023 National Survey of Children’s Health, this study examined disparities in (1) any weekly physical activity and (2) participation in organized sport among transition-age youth (14-17 years) with ASD only, ID only, or ASD + ID, compared with youth without ASD or ID. Survey-weighted multiple logistic regression models estimated adjusted odds ratios (aORs) for each outcome, controlling for sex, race, household poverty ratio, metropolitan residence, and age. Compared to youth without ASD or ID, all diagnostic groups had significantly lower odds of engaging in any weekly physical activity (ASD only: aOR = 0.32, 95% CI: 0.24-0.44; ID only: aOR = 0.49, 95% CI: 0.31-0.76; ASD + ID: aOR = 0.51, 95% CI: 0.30-0.88; all p ≤ 0.02) and organized sport (ASD only: aOR = 0.20, 95% CI: 0.15-0.27; ID only: aOR = 0.31, 95% CI: 0.19-0.51; ASD + ID: aOR = 0.24, 95% CI: 0.14-0.41; all p < 0.001). Across both models and diagnostic groups, female sex, lower household income, and increased age were associated with lower physical activity and sport participation (all p ≤ 0.02), whereas non-metropolitan residence was associated with higher odds of sport participation-only (p = 0.005). These findings identify substantial disengagement among youth with ASD and/or ID and highlight the need for accessible, adapted physical activity and sport opportunities during adolescence to reduce risk of long-term inactivity. Adolescents with autism and/or intellectual disability are less likely to take part in weekly physical activity and sports than their peers without these conditions. Lower engagement was most pronounced for autistic youth without intellectual disability. The findings point to a need for more inclusive and sustainable physical activity and organized sport opportunities before support services decline in adulthood. eng

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14. Lopez-Espejo M. Trends in the age-standardized prevalence of neurodevelopmental disorders in South America, 1990-2023. Arq Neuropsiquiatr;2026 (May);84(5):1-8.

BACKGROUND: Neurodevelopmental disorders (NDDs) are substantial burdens for individuals and health systems; yet, their long-term epidemiology in South America is poorly characterized. OBJECTIVE: To describe the trends from 1990 to 2023 in the age-standardized prevalence rates (ASPRs) of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and idiopathic developmental intellectual disability (IDID) across 12 South American countries using Global Burden of Disease (GBD) 2023 estimates. METHODS: Country-specific annual ASPRs and 95% uncertainty intervals (95%UIs) were obtained from the GBD 2023. Sex-stratified ASPRs were used to calculate male-to-female ratios (MFRs) and summarize long-term sex disparities. Temporal trends were assessed using the average annual percent change (AAPC) from log-linear regression for each country. RESULTS: In 2023, the ASPRs ranged from 0.57 to 1.06% for ASD, from 1.00 to 2.55% for ADHD, and from 0.42 to 0.54% for IDID across countries. Between 1990 and 2023, the ASD ASPRs increased in all countries, with AAPCs from +0.35%/year (Paraguay) to +0.79%/year (Chile). The ADHD ASPRs showed little net change, with AAPCs from -0.10%/year (Argentina) to +0.39%/year (Brazil). And the IDID ASPRs declined consistently, with AAPCs from -0.79%/year (Bolivia) to -0.30%/year (Suriname). Sex differences in ASPRs were large and persistent for ASD and ADHD, but small for IDID. The MFR trajectories suggested a slight widening of the ASD male-female gap, largely stable ADHD disparities, and minimal variability for IDID. CONCLUSION: Over 3 decades, the ASD ASPRs rose modestly, the ADHD ASPRs were broadly stable, and the IDID ASPRs declined across South America. The GBD 2023 estimates point to enduring diagnostic and structural inequities and to the need for strengthened surveillance and more equitable access to developmental assessment.

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15. Mihaylova V, Kovacheva E, Gevezova M, Sarafian V, Kazakova M. Mitochondria as an Integrative Hub of Cellular Homeostasis and Stress Response. Int J Mol Sci;2026 (Apr 27);27(9)

Mitochondria are increasingly recognized as multifunctional organelles that integrate metabolic, redox, immune, and cell fate signaling, thereby maintaining cellular and tissue homeostasis under physiological conditions. Beyond their classical role in ATP production, mitochondria act as central regulatory hubs coordinating adaptive responses to metabolic demands and environmental stress. These functions are sustained through tightly regulated quality control mechanisms, including mitochondrial biogenesis, dynamic fusion-fission remodeling, redox signaling, and selective removal of damaged organelles via mitophagy. Disruption of these processes compromises cellular resilience and contributes to disease initiation and progression. This review summarizes and critically evaluates current evidence on mitochondrial function in health and its dysregulation in pathological conditions, with a particular focus on rheumatoid arthritis (RA), ischemic stroke (IS), and autism spectrum disorder (ASD). Despite their distinct clinical manifestations, these disorders share convergent mitochondrial abnormalities, including metabolic reprogramming toward glycolysis, excessive or persistent reactive oxygen species production, impaired mitophagy, mitochondrial DNA-driven innate immune activation, and hypoxia-related stress. In RA, mitochondrial dysfunction sustains chronic inflammation and joint destruction; in IS, acute mitochondrial failure and reperfusion-associated oxidative stress drive neuronal injury; and in ASD, mitochondrial metabolic inflexibility and defective quality control contribute to chronic low-grade inflammation and neurodevelopmental vulnerability. A variety of methods for the assessment of mitochondrial function are available to study these pathological conditions. Collectively, these findings position mitochondrial dysfunction as a unifying pathogenic mechanism linking inflammatory, neurodegenerative, and neurodevelopmental processes. Targeting mitochondrial metabolism, redox balance, and quality control pathways therefore represents a promising cross-disease therapeutic strategy.

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16. Mortazavi M, Guevara J, Diaz J, Tran S, Ziaei Jam H, Reeves C, Batalov S, Jepsen K, Bainbridge M, Besterman AD, Gymrek M, Palmer AA, Sebat J. Long-read genome sequencing improves detection and functional interpretation of structural and repeat variants in autism. Cell Genom;2026 (May 13);6(5):101186.

Long-read whole-genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). We performed LR-WGS on 267 individuals from 63 autism spectrum disorder (ASD) families and generated an integrated call set combining long- and short-read data. LR-WGS increased detection of gene-disrupting SVs and TRs by 33% and 38%, respectively, and enabled identification of novel exonic de novo germline and somatic SVs. We observed complex SV patterns, including a class of nested duplication-deletion events. By joint analysis of phased genetic variation and DNA methylation, we identified deletions of imprinted genes and demonstrated the effect of intermediate TR expansions (35-54 CGG) on the methylation of FMR1 promoter. Rare SVs, TRs, and damaging SNVs together accounted for 7.4% (95% confidence interval [CI], 2.7%-17%) of the heritability of ASD. These findings demonstrate how LR-WGS can resolve complex genetic variation and its functional consequences and regulatory effects in a single assay.

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17. Osredkar J, Fabjan T, Godnov U, Jekovec-Vrhovšek M, Osredkar D, Finderle P, Kumer K, Zorec M, Fanedl L, Avguštin G. Microbiome-Derived Short-Chain Fatty Acids and Tryptophan Metabolites in Children with Autism Spectrum Disorder: A Stool-Urine Multi-Omics Analysis. Int J Mol Sci;2026 (Apr 29);27(9)

Autism spectrum disorder (ASD) has been associated with alterations in the gut microbiota and its metabolites, particularly short-chain fatty acids (SCFAs) and microbiota-derived tryptophan catabolites, which may influence neurodevelopment through immune and epigenetic mechanisms. We investigated whether stool SCFAs and tryptophan-pathway metabolites differ between children with ASD and typically developing controls, and whether these metabolites associate with ASD severity and systemic biochemical signatures. In this cross-sectional study, we analyzed stool samples from 229 children (160 with ASD, 69 controls) with complete SCFA and tryptophan-metabolite data, while urine metabolomics data were available for a subset and were used for exploratory stool-urine integration analyses. Children with ASD and controls were similar in age, but the ASD group had a higher proportion of males. Absolute concentrations of individual SCFAs, total SCFAs, and derived indices were broadly comparable between groups; nominal differences in propionate/acetate ratio and caproate did not remain significant after false discovery rate correction. Similarly, stool tryptophan-pathway metabolites reported as ng/a.u. based on the NanoDrop-derived proxy (tryptophan, kynurenine, indole-3-acetic, indole-3-lactic, indole-3-propionic, indole-3-aldehyde, N-acetyl-tryptophan, serotonin, melatonin, tryptamine) and functional ratios (kynurenine/tryptophan, indole-derived/tryptophan, serotonin/tryptophan) showed no robust ASD-control differences; N-acetyl-tryptophan was nominally higher in ASD but did not survive multiple-testing correction. In the ASD subgroup with available Childhood Autism Rating Scale (CARS) data (n = 34), SCFA and tryptophan indices showed only weak, non-significant correlations with global ASD severity. In contrast, correlation analyses revealed two coherent metabolic modules, i.e., an SCFA block with very strong internal correlations among individual SCFAs and total SCFAs and a tryptophan block with strong correlations between metabolites and their normalized ratios, while cross-module correlations were modest. These results indicate that stool SCFA and microbiota-derived tryptophan profiles do not robustly distinguish ASD from controls in this cohort, but they form stable metabolic modules compatible with microbiome-epigenome frameworks.

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18. Ramiro-Cortés Y, Panzarino AM, Royo M, Shionoya K, Israely I. Dysfunctional synaptic competition at dendritic spines in Fragile X syndrome. bioRxiv;2026 (Feb 26)

Dendritic spines are highly dynamic structures whose morphology and lifespan are modified in response to synaptic efficacy changes. Structural modifications following activity support the long-term encoding of information and could allow for the remodeling of neural circuits. Long-term depression (LTD) is a key mechanism for synaptic weight regulation, yet its structural correlates – particularly for long-lasting, protein synthesis dependent forms – remain poorly understood. Furthermore, in humans, this type of plasticity is often disrupted in neurodevelopmental disorders, correlating with cognitive dysfunction and structural abnormalities. Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and is characterized by excessive metabotropic receptor-mediated synaptic depression, excessive protein synthesis, and spine abnormalities. Here, we investigate the relationship between long lasting synaptic depression and structural plasticity, as well as the role of protein availability in determining how many spines can simultaneously undergo structural changes during LTD in both healthy and FXS mutant neurons. Using high resolution optical methods, we developed and tested a method for inducing metabotropic glutamate receptor (mGluR)-dependent depression at single spines via glutamate uncaging in mouse hippocampal neurons. We found that this form of activity leads to robust spine shrinkage, which requires new protein synthesis. However, when we induced this depression at multiple spines, they competed for structural changes and only one spine shrank. We hypothesized that this was due to limited resources, in the form of newly made proteins, and therefore, we decided to test if spine competition would be altered in the mouse model of FXS, where protein levels are abnormally elevated. Indeed, we found that competition was absent in FXS mutant neurons, and all of the stimulated spines underwent shrinkage following LTD induction. Importantly, we found that single spine structural plasticity in FXS was expressed to the same degree as in WT controls. Taken together, these findings suggest that the hallmark phenotype of excess mGluR LTD in FXS may result from a greater number of inputs undergoing synaptic depression, rather than excessive LTD at individual synapses. By probing plasticity at the level of individual inputs, our findings highlight the importance of evaluating activity across groups of synapses, in order to uncover plasticity interactions that are critical for learning. Understanding how these mechanisms are disrupted in neurodevelopmental disorders such as FXS can inform the development of effective therapeutic strategies.

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19. Shukla A, Rivera EL, Bladon JH, Jadhav SP. A novel cooperative behavior assay in rats reveals distinct social coordination strategies of increasing complexity and social reciprocity deficits in a model of Fragile-X Syndrome. J Neurosci;2026 (May 13)

Cooperative behavior, the ability of individuals to coordinate their actions toward shared goals, is fundamental to survival and social success across species. However, the mechanisms supporting cooperation and disruptions leading to social deficits in neurodevelopmental disorders such as autism spectrum disorder remain poorly understood. To address these questions, we developed a novel cooperation task in which rat pairs had to visit matching reward wells on paired spatial mazes under deterministic and probabilistic reward contingencies, utilizing dyads of littermate wild-type (WT) and Fmr1 knockout (Fmr1) rats, a model of Fragile X syndrome. Both WT and Fmr1 male rat pairs exhibited dynamic turn-taking with mixed leader-follower behavior for cooperation; however, WT pairs achieved significantly greater cooperation success than Fmr1 pairs. WT and Fmr1 pairs both successfully utilized a simple follower-tracking-leader strategy, resulting in slower asynchronous transitions between reward wells, with Fmr1 pairs more reliant on this reactive strategy. WT rat pairs also exhibited a more efficient and flexible predictive cooperation strategy, requiring anticipation and coordination of optimal transition patterns with peers, resulting in faster synchronous transitions. Fmr1 rats were unable to utilize this more efficient social reciprocity strategy of higher complexity, leading to deficits in adapting to the probabilistic reward condition and in cooperative behavior. These findings reveal distinct strategies of varying complexity for cooperation, demonstrate the existence of a complex predictive social reciprocity strategy in WT rats and it’s disruption in a rat autism model, providing a foundation for investigating mechanisms underlying social interactions with relevance to neurodevelopmental disorders.Significance statement Successful cooperation requires monitoring others’ actions and flexibly adjusting self-behavior, yet mechanisms underlying cooperation and associated deficits in neurodevelopmental disorders such as autism remain unclear. Using a novel spatial cooperation task in rats, we identify hierarchical strategies that support cooperative behavior – a simpler follower-tracking-leader reactive strategy, and a more complex reciprocity-based predictive strategy that enabled synchronized coordination of actions with peers. While both WT and Fmr1 rats exhibited the slower reactive strategy, only WT rats flexibly adopted more complex predictive strategies for efficient cooperation. Fmr1 rats thus showed selective disruption in social reciprocity due to impaired ability to predict and synchronize with partner actions. These findings provide a novel framework for dissecting the behavioral and neural mechanisms underlying social cooperation.

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20. Siqueira LPC, Bermúdez VA, Gomes VF, de Paula Francisco GC, Alckmin-Carvalho F, Bhattacharya P, Surtees ADR, Teixeira M. Intersectoral Collaboration Between Educational and Mental Health Services for Autistic Children and Adolescents in Brazil. Healthcare (Basel);2026 (Apr 27);14(9)

INTRODUCTION/OBJECTIVES: Intersectoral collaboration between education and mental health services is central to the care of autistic children and adolescents. However, recent literature indicates that evidence remains limited regarding how these collaborative arrangements are implemented in routine public services, particularly in low- and middle-income countries (LMICs). This study aimed to assess the intersectoral collaboration between Brazilian educational and mental health services for autistic children and adolescents and to examine the frequency and type of intersectoral contact. METHODS: An exploratory cross-sectional study was conducted in the municipal public education system of Niterói, a city in the Southeast region of Brazil. Participants included parents of 123 autistic children and adolescents, 49 teachers from mainstream education and specialized educational services (SES), and 24 health professionals. Data were collected using structured questionnaires with multi-informant reports. The instruments were specifically developed for the study and submitted to expert content-validation procedures. Analyses included descriptive statistics and, in a subsample of 51 matched cases with paired responses from teachers and health professionals, Cohen’s kappa to assess agreement between reports. RESULTS: Low levels of intersectoral collaboration were observed, characterized by infrequent contact, limited information exchange, and slight agreement between reports from teachers and health professionals (κ = 0.25; p = 0.01). Teachers were more likely to know where care was provided than to know which specialists were involved, while more than half of health professionals did not know which school the child attended. CONCLUSIONS: In the investigated municipal network, care appeared fragmented, highlighting difficulties in translating intersectoral recommendations from public policies into routine collaborative practices.

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21. Son JY, Do Y, Seo J, Choi J. Gut-Derived Metabolic Imbalance in Autism Spectrum Disorder: Toward the Concept of a Metabolic Subtype. Nutrients;2026 (Apr 30);18(9)

Autism spectrum disorder (ASD) is highly heterogeneous in symptom onset and severity, comorbidities, and treatment responsiveness, challenging the notion of a single pathogenic mechanism. Increasing evidence indicates that some individuals with ASD exhibit prominent peripheral physiological alterations, including gastrointestinal (GI) dysfunction, gut microbial dysbiosis, immune imbalance, oxidative stress, and mitochondrial/energy metabolic vulnerability. In this context, gut-derived metabolites-particularly short-chain fatty acids (SCFAs)-have emerged as plausible modulators of the neurodevelopmental milieu through the expanded gut-immune-metabolic-brain axis. This review synthesizes: (i) SCFAs’ biogenesis and physiological roles, (ii) context- and developmental stage-dependent effects, (iii) the clinical heterogeneity of reported microbiome and SCFA alterations in ASD, and (iv) propionate as a frequently discussed candidate signal and the interpretive boundaries of preclinical evidence. Human studies show substantial inter-study variability in SCFA alterations (increases, decreases, or no differences), influenced by factors such as sample type (stool vs. blood), GI symptoms, diet, medication exposure, and analytical variability. Accordingly, SCFAs should not be treated as universal ASD biomarkers but rather as context-dependent metabolic signals relevant under specific clinical and biological conditions. Building on this premise, we propose the conceptual framework of « metabolic ASD » representing a metabolically informed dimension of biological variability in which peripheral metabolic-immune perturbations may contribute to neurodevelopmental vulnerability. To avoid premature causal claims, we outline design requirements for future research, including stratified study designs, longitudinal cohorts, and integrative multi-layer analyses. Ultimately, metabolic ASD should be positioned as a testable precision medicine research framework rather than a universal etiological model.

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22. Song W, McQuaid GA, Charlton RA, Wallace GL. Longitudinal Association Between Social Support and Quality of Life Among Middle-Aged and Older Autistic Adults. Autism;2026 (May 13):13623613261446878.

Social support is positively associated with quality of life (QoL) in autistic people, yet almost all evidence is cross-sectional and focused on younger adults. We examined 2-year longitudinal survey data from 209 autistic adults aged ⩾40 years living in the United States, all recruited via the Research Match service of Simons Powering Autism Research for Knowledge. Participants self-reported their general QoL, autism-specific QoL, and social support (subjective support, instrumental support, and social interaction). Cross-lagged panel models tested bidirectional associations. Mean scores increased from Time 1 to Time 2 for the general QoL and autism-specific QoL, while social support was mostly stable. Higher baseline general QoL predicted greater subjective support later, whereas baseline subjective support did not predict later general QoL. A reciprocal relationship emerged between autism-specific QoL and subjective support. Unexpectedly, baseline instrumental support predicted lower subsequent general QoL. Among autistic adults in mid-to-later life, QoL appears to drive subsequent social support more strongly than support drives QoL, with the clearest reciprocity observed for autism-specific QoL and subjective support. Future multiwave studies with more diverse samples are needed to chart long-term trajectories and determine how tailored support can optimize aging outcomes in individuals with autism.Lay AbstractWe know little about how autistic people’s perceived social support and quality of life (QoL) influence each other as they age. We surveyed 209 40+-year-old autistic adults living in the United States at two timepoints 2 years apart. They answered questions about their general QoL, QoL specific to their autistic experiences, and three types of social support (subjective support, instrumental support, and social interaction). The first survey was in late 2019/early 2020, and the second was 2 years later – late 2021/early 2022. We found that, on average, middle-aged and older autistic adults reported better QoL after 2 years, while the amount of practical help and the number of social interactions did not change. People who started out with better QoL reported more subjective support later. Reporting better autism-specific QoL at the beginning led to more emotional and practical support later and vice versa – feeling well-supported emotionally initially led to better autism-specific QoL later. Surprisingly, getting more initial practical support was linked to lower overall QoL 2 years later. Our results suggest that helping autistic adults feel comfortable with their identity, manage sensory needs, and navigate services may not only improve their QoL but also strengthen the emotional and practical support they receive from others. Practical help is still important, but it should match the person’s goals and preferences, so that it boosts, rather than harms, life satisfaction. Programs that check in regularly about changing needs, especially around significant life events like retirement or health changes, could make a real difference as autistic adults grow older.

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23. Vinci M, Musumeci A, Treccarichi S, Virgillito M, Calì S, Gloria A, Federico C, Saccone S, Elia M, Calì F. A De Novo USP24 Variant as a Candidate Driver in a Neurodevelopmental Disorder: Insights from Trio-Based Whole-Exome Sequencing. Int J Mol Sci;2026 (May 2);27(9)

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), are increasingly recognized as conditions with a complex, multisystemic origin. ASD frequently co-occurs with other neurological conditions, such as epilepsy. We report a female patient, born to unrelated healthy parents, presenting with a complex clinical phenotype characterized by ASD level 1 with fluent speech, borderline intellectual functioning (BIF), coordination disorder, and epilepsy. Trio-based whole-exome sequencing (WES) revealed a de novo variant in the USP24 gene (c.3155G>T; p.Ser1052Ile), classified as likely pathogenic according to ACMG criteria (PS2, PM2, PP2, BP4). USP24 has previously been associated with Parkinson’s disease and has recently emerged as a candidate risk gene for ASD. In addition, WES detected two variants of uncertain significance (VUS), both inherited from the clinically unaffected father: c.388G>C (p.Gly130Arg) in NRXN2 and c.6395C>A (p.Ser2132Tyr) in LRP2. Although neither gene shows a fully penetrant causal relationship with the observed phenotype, both have been implicated in neurodevelopmental disorders. Array-CGH analysis did not reveal pathogenic copy number variants; however, the presence of additional genetic contributors not detectable by WES cannot be excluded. Overall, the de novo USP24 variant likely represents the primary genetic driver of the phenotype, while the potential contribution of the inherited NRXN2 and LRP2 variants remains plausible. This case underscores the complexity of the genetic architecture underlying NDDs and supports a model involving cumulative effects of multiple variants rather than a strictly multigenic interaction.

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24. Vlasiu AR, Frincu ME. Private Ensembles, Public Confidence: A PATE-to-MedPrompt System for Autism Detection. Diagnostics (Basel);2026 (Apr 25);16(9)

Background/Objectives: Early autism screening needs to be both accurate and privacy-preserving, but single-source assessments can miss clinically important context. We therefore study a preliminary integrated framework that combines privacy-preserving questionnaire-based risk estimation with a second reasoning component based on a large language model (LLM) that evaluates symptom narratives. The objective is to test whether structured screening outputs can be translated into uncertainty-aware narrative reasoning within one privacy-conscious workflow. Methods: The proposed pipeline links a PATE-style AQ-10 screening stage to a MedPrompt-style consensus reasoning stage that operates on behavioral summaries and transcript-style inputs. Evaluation includes component-wise testing on AQ-10 data, an end-to-end controlled setting, synthetic stress testing, and transcript-only analysis on 26 examples. Results: In component-wise evaluation, the combined pipeline reaches ceiling performance on a controlled AQ-10 split, synthetic stress testing reduces accuracy to 97.2%, and transcript-only testing shows that contextual factors such as age substantially improve sensitivity. Conclusions: These findings support only a highly preliminary proof-of-concept under constrained evaluation conditions and should be interpreted as motivation for broader external validation rather than as evidence of practical decision-support readiness across settings.

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25. Wang Y, Zhang Y, Zhang L, Tao H, Zhang T, Shao Z. Own-name processing in toddlers with autism spectrum disorder: ERP evidence from an auditory oddball paradigm. Front Psychiatry;2026;17:1780724.

INTRODUCTION: Reduced responsiveness to hearing one’s own name is a core early behavioral predictor of autism spectrum disorder (ASD). This behavioral maker reflects atypicalities in self-related and social auditory processing, that are foundational to the development of social communication. To better understand the underlying neural mechanism of this alteration, the current study investigated neural correlates of auditory own-name processing in a sample of toddlers with ASD and typically developing (TD) controls using an auditory novelty oddball paradigm. METHODS: Participants included 54 toddlers (30 ASD, 24 TD; 2-4 years) who passively listened to five auditory stimuli consisted of pure tones (500Hz and 1000Hz) and name types (self, familiar and stranger names). An auditory novelty oddball paradigm was utilized to assess neural response to standard and deviant stimuli, as well as to the different name types. Event-related potentials (ERPs) were recorded to measure neural activity during the stimulus processing. RESULTS: Compared to TD controls, autistic toddlers showed reduced late MMN to deviant tones that was infrequently presented relative to standard tones; Analysis of ERP components during own-name processing revealed atypical neural response pattern: autistic toddlers exhibited enhanced central P3a coupled with decreased LDN amplitudes to one’s own-name relative to other names, and lack of parietal LPP effect typically observed in response to one’s own-name. DISCUSSION: Our findings provide insight into the neural mechanisms underlying altered own-name processing in toddlers with ASD. These results suggest preserved early attentional capture of self-relevant salience, but atypical higher-order cognitive functioning during self-related and social auditory processing in toddlers with ASD.

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26. Yoon CD, Meadan H, Shic F. Towards the ecological automated measurement of joint attention: Development of an interactive eye-tracking battery for joint attention in children with and without autism. Behav Res Methods;2026 (May 13);58(6)

Eye tracking has emerged as a powerful tool for advancing autism research, including diagnostics and interventions. However, studies on joint attention (JA) in autistic children have predominantly concentrated on the responding to joint attention (RJA) construct, with limited focus on the initiating joint attention (IJA) construct. Moreover, despite the interactive nature of JA, researchers have often relied on passive paradigms to study JA in this population. To address these gaps, we developed a gaze-contingent eye-tracking battery targeting three developmentally appropriate JA skills for young children: RJA, IJA to request, and IJA to comment or reference. The development process was multifaceted and iterative, involving a series of collaborative steps and the allocation of various resources. These steps included determining the motion format and stimulus type, designing and prototyping the stimuli, recruiting an actor to serve as a communication partner in the stimuli, recording and editing videos for the stimuli, and building and test-running the battery. We developed the Interactive Eye Tracking for Joint Attention (IET-JA) battery, which consists of 32 JA stimuli: 16 RJA, 8 IJA-Request, and 8 IJA-Comment/Reference. The stimuli are dynamic (i.e., videos) and feature a preprogrammed interactive human communication partner who is responsive to the participant’s gaze. The IET-JA takes approximately 8 minutes to complete, and its duration is expected to vary based on the participant’s level of engagement. Implications for advancing methodologies, fostering team science, and enhancing iterative processes are discussed.

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