1. Erratum: Study on the Therapeutic Effect of Yu-Mu-Tiao-Shen Acupuncture on Rats with Autism Spectrum Disorder [Corrigendum]. Neuropsychiatr Dis Treat. 2025; 21: 2869-70.

[This corrects the article DOI: 10.2147/NDT.S543628.].

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2. Al-Ajlouni YA, Lihaz M, Islam M. A pediatric case of diphthamide biosynthesis 1 gene defect presenting with developmental delay, short stature, dysmorphic features, and sparse hair (Loucks-Innes syndrome): a case report. J Med Case Rep. 2025; 19(1): 641.

BACKGROUND: Diphthamide biosynthesis 1 is a critical component of the multiprotein complex responsible for diphthamide biosynthesis. Autosomal recessive variants in Diphthamide biosynthesis 1 gene are associated with an ultra-rare neurodevelopmental disorder called developmental delay with short stature, dysmorphic facial features, and sparse hair, also known as Loucks-Innes syndrome. To the best of our knowledge, there have been fewer than 20 reported cases of Loucks-Innes syndrome in the literature. CASE REPORT: We present a 14-year-old Yemeni male patint with novel homozygous variants in diphthamide biosynthesis 1, who presented with a history of congenital hydrocephalus, neonatal seizures, dysmorphic face, and sparse hair. The patient also had aortic root dilation, intellectual disability, short stature, hypoplastic toenails, and mixed conductive and sensorineural hearing loss in both ears. He was only able to move around by crawling and was confined to a wheelchair. CONCLUSION: This case report adds to the limited knowledge on developmental delay with short stature, dysmorphic facial features, and sparse hair and highlights the importance of genetic workup in patients with intellectual disability, short stature, and craniofacial and ectodermal anomalies. Further research is needed to better understand the pathogenesis and clinical features of this rare syndrome.

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3. Alatrash S, Paul T, Andrade BF, Monga S, Brian J, Anagnostou E, Penner M, Fekr AR, Kushki A. Irritability in autism examined through network analysis of phenotypic and physiological correlates. Sci Rep. 2025; 15(1): 44553.

Symptoms of irritability are commonly reported in autism, yet correlates of this domain remain poorly understood. While prevalence estimates in the literature vary considerably, they range up to 80%. Irritability can interfere with daily functioning, social relationships, and academic performance. Despite years of research and the availability of approved medications, intervention outcomes for irritability remain highly variable. To advance understanding and inform more targeted, personalized interventions, the present study aimed to clarify the correlates of irritability in autism using network analysis, an analytical tool suited to capture complex associations across interconnected variables. We examined demographic, phenotypic, and physiological factors in a sample of autistic and neurotypical children. Our findings identified strong direct associations between irritability and externalizing behaviors, emotion dysregulation, autism features, and negative affect. Physiological responses, including heart rate reactivity and variability, were indirectly connected to irritability through links with self-regulation abilities and ADHD traits. These results highlight the importance of conceptualizing irritability in autism as part of a broader, interconnected network of influences rather than an isolated symptom. Recognizing these relationships informs potential targets for future intervention studies.

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4. Aydin A, Yildirim A, Kara O, Mwenda Z. Mixed-Frequency rTMS Rapidly Modulates Multiscale EEG Biomarkers of Excitation-Inhibition Balance in Autism Spectrum Disorder: A Single-Case Report. Brain Sci. 2025; 15(12).

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established neuromodulatory method, yet its multiscale neurophysiological effects in autism spectrum disorder (ASD) remain insufficiently characterized. Recent EEG analytic advances-such as spectral parameterization, long-range temporal correlation (LRTC) assessment, and connectivity modeling-enable quantitative evaluation of excitation-inhibition (E/I) balance and network organization. Objective: This study aimed to examine whether an eight-session, EEG-guided mixed-frequency rTMS protocol-combining inhibitory 1 Hz and excitatory 10 Hz trains individualized to quantitative EEG (qEEG) abnormalities-produces measurable changes in spectral dynamics, temporal correlations, and functional connectivity in a pediatric ASD case. Methods: An 11-year-old right-handed female with ASD (DSM-5-TR, ADOS-2) underwent resting-state EEG one week before and four months after intervention. Preprocessing used a validated automated pipeline, followed by spectral parameterization (FOOOF), detrended fluctuation analysis (DFA), and connectivity analyses (phase-lag index and Granger causality) in MATLAB (2023b). No inferential statistics were applied due to the single-case design. The study was conducted at Cosmos Healthcare (London, UK) with in-kind institutional support and approved by the Atlantic International University IRB (AIU-IRB-22-101). Results: Post-rTMS EEG showed (i) increased delta and reduced theta/alpha/beta power over central regions; (ii) steeper aperiodic slope and higher offset, maximal at Cz, suggesting increased inhibitory tone; (iii) reduced Hurst exponents (1-10 Hz) at Fz, Cz, and Pz, indicating decreased long-range temporal correlations; (iv) reorganization of hubs away from midline with marked Cz decoupling; and (v) strengthened parietal-to-central directional connectivity (Pz→Cz) with reduced Cz→Pz influence. Conclusions: Mixed-frequency, EEG-guided rTMS produced convergent changes across spectral, aperiodic, temporal, and connectivity measures consistent with modulation of cortical E/I balance and network organization. Findings are preliminary and hypothesis-generating. The study was supported by in-kind resources from Cosmos Healthcare, whose authors participated as investigators but had no influence on analysis or interpretation. Controlled trials are warranted to validate these exploratory results.

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5. Bell RR, Thomas HR, Saffran JR, Eigsti IM. A systematic review of statistical learning in autism spectrum disorder. Mol Autism. 2025.

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6. David D, Baxter P, Belpaeme T, Billing E, Cai H, Cao HL, Ciocan A, Costescu C, Hernandez Garcia D, Gómez Esteban P, Kennedy J, Liu H, Matu S, Mazel A, Selescu M, Senft E, Thill S, Vanderborght B, Vernon D, Ziemke T. Efficacy and effectiveness of robot-assisted therapy for autism spectrum disorder: From lab to reality. Sci Robot. 2025; 10(109): eadl2266.

The use of social robots in therapy for children with autism has been explored for more than 20 years, but there still is limited clinical evidence. The work presented here provides a systematic approach to evaluating both efficacy and effectiveness, bridging the gap between theory and practice by targeting joint attention, imitation, and turn-taking as core developmental mechanisms that can make a difference in autism interventions. We present two randomized clinical trials with different robot-assisted therapy implementations aimed at young children. The first is an efficacy trial (n = 69; mean age = 4.4 years) showing that 12 biweekly sessions of in-clinic robot-assisted therapy achieve equivalent outcomes to conventional treatment but with a significant increase in the patients’ engagement. The second trial (n = 63; mean age = 5.9 years) evaluates the effectiveness in real-world settings by substituting the clinical setup with a simpler one for use in schools or homes. Over the course of a modest dosage of five sessions, we show equivalent outcomes to standard treatment. Both efficacy and effectiveness trials lend further credibility to the beneficial role that social robots can play in autism therapy while also highlighting the potential advantages of portable and cost-effective setups.

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7. Deshpande N, Nair S, Taylor E, Van Someren EJW, Chellappa SL. Associations of autistic traits, sleep/circadian factors, and mental health in a community-based survey study. J Affect Disord. 2025; 398: 121019.

Autistic individuals experience a heightened risk of depression and lower quality of life; however, the biological underpinnings for this increased risk remain to be fully established. We assessed whether disruption of self-reported sleep and circadian factors mediates the associations of autistic traits with depression symptom severity and quality of life in a community-based survey study. A total of 838 participants (mean: 52.8 [SD = 1.3] years, 70 % females) from a large-scale observational survey completed the Autism Quotient Scale, Hospital Anxiety and Depression Scale, Cantril Ladder quality of life, Insomnia Severity Index, Pittsburgh Sleep Quality Index, and the Munich Chronotype Questionnaire. Higher autistic traits were significantly associated with higher depression symptom severity (p = 0.04) and significantly lower quality of life (p < 0.001). Insomnia severity and later chronotype partly mediated the association of autistic traits and depression symptom severity (respectively, β = -0.02, 95 % CI -0.03, -0.01; β = -0.02, 95 % CI =[-0.04, -0.01). Likewise, insomnia severity and later chronotype partly mediated theassociation of autistic traits with lower quality of life (respectively, β = - 0.09, 95 % CI -0.14, -0.02; β = -0.05, 95 % CI = -0.09, -0.01). Our findings indicate that autistic traits are associated with higher depression severity and lower quality of life, mediated by insomnia and chronotype. Future studies targeting insomnia complaints and later chronotype in autistic people may help alleviate their mental health complaints and increase quality of life.

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8. Eissenberg JC. Autism Spectrum Disorder: Nature vs. Nurture. Mo Med. 2025; 122(6): 501-7.

Autism Spectrum Disorder (ASD) is associated with a variety of inherited disorders, but most diagnoses have no identifiable genetic etiology. There has been a significant increase in the incidence of ASD diagnoses in the past three decades. The now-discredited vaccine theory of ASD causation has driven concerns over environmental exposures that may or may not lead to ASD. Here, I discuss the evidence for an underlying genetic basis for ASD, the evidence that environmental inputs could play a significant role ASD and potential treatments for associated symptoms.

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9. Errico F, Russo R, Carrillo F, Nuzzo T, di Vito R, Canonico E, Pedone PV, Di Cunto F, Esposito T, Usiello A, Chambery A. Free D-aspartate modulates the expression of proteins linked to schizophrenia and autism spectrum disorder during early postnatal life. Cell Mol Life Sci. 2025; 83(1): 3.

D-aspartate is an endogenous agonist of NMDA and mGlu5 receptors, with a distinctive spatiotemporal expression profile that peaks in the prenatal and early postnatal brain. This suggests a critical role for D-aspartate metabolism in modulating neurodevelopmental processes linked to glutamatergic neurotransmission. However, the precise mechanisms through which D-aspartate exerts its effects remain unclear. To elucidate the molecular pathways orchestrated by early D-aspartate signalling, we employed a knock-in mouse model characterized by constitutive D-aspartate depletion due to the prenatal expression of its degradative enzyme, D-aspartate oxidase. Using an advanced quantitative proteomic approach based on Tandem Mass Tag isobaric labelling and nano-liquid chromatography coupled with high-resolution tandem mass spectrometry, we investigated the proteomic variations induced by D-aspartate depletion during postnatal brain development, comparing Ddo knock-in mice with their wild-type littermates. Our findings reveal that D-aspartate modulates the neonatal expression of proteins involved in glutamatergic neurotransmission, nervous system development, and cytoskeleton organization. Moreover, proteomic analysis identified a subset of D-aspartate-regulated proteins mapping molecular pathways associated with autism spectrum disorder and schizophrenia. These findings offer new perspectives on the complex protein networks influenced by D-aspartate metabolism in the developing brain and highlight its potential impact on cerebral function in health and psychiatric disorders.

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10. Hai Y, Bai S, Qiao H, Li D, Wang D, Xia M. A Review of Therapeutic Approaches for Autism Spectrum Disorder. Brain Sci. 2025; 15(12).

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Significant progress has been made in the intervention and treatment of ASD. This review systematically summarizes five major categories of mainstream ASD treatment approaches. This article outlines the theoretical basis and therapeutic effects of each intervention method, discusses their advantages and limitations, and analyzes and forecasts future development directions. Due to the lack of specific treatment methods, ASD treatment primarily relies on behavioral interventions, supplemented by symptomatic pharmacological treatments. Behavioral interventions can significantly improve children’s self-care abilities and quality of life while also promoting social skills and communication, and reducing disability and comorbidity rates. ASD intervention methods should primarily focus on those proven effective through evidence-based practice, adhering to individualized, multidimensional, and multidisciplinary approaches, thereby promoting the development and establishment of efficient and personalized intervention strategies.

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11. Hebrink D, Bruene D, Fowler C, Pelzel K, Hanrahan K. Improving the Venipuncture Experience in Children with Autism Spectrum Disorder. Am J Nurs. 2026; 126(1): 34-41.

BACKGROUND: Children with autism spectrum disorder (ASD) may experience heightened fear and distress when accessing health care services, which can result in noncompliance with procedures. Management of needle pain and fear is particularly important for children with ASD given their higher utilization of health care services, neurodiversity, and limited coping skills. PURPOSE: The purpose of this quality improvement project was to implement and evaluate evidence-based interventions to improve procedural care processes and challenging behaviors in children with ASD undergoing venipuncture. METHODS: The Iowa Model was used to guide evidence-based practice (EBP) improvement in the care of children with ASD undergoing venipuncture at a pediatric procedure and imaging suite of a children’s hospital at an academic medical center. Based on evidence from the literature, patient and family preferences, and clinician input, a practice change that included individualized care, patient and family preparation, clinician preparation, and system design was implemented. RESULTS: Sixteen clinicians, including RNs, medical assistants, and nursing assistants, demonstrated increased knowledge and comfort in caring for children with ASD, improved availability of resources, improved utilization of procedure support cues and workflows, and improved outcomes. Similarly, 20 parents of children with ASD demonstrated improved preparedness, staff comfort, appointment flow, supportive environment, and awareness of individual needs and communication. Process measures were used to identify opportunities for improvement, select implementation strategies, and design the practice change. CONCLUSIONS: Improvement in individualized care, patient and family preparation, clinician preparation, and system design can optimize care of children with ASD undergoing venipuncture procedures. An EBP process model and multiple targeted implementation strategies may facilitate the adoption of interventions to support these children.

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12. Mullin BH, Stuckey M, Brown SJ, Mullin S, Campbell PJ, Dudbridge F, Menni C, Walsh JP, Whitehouse AJO, Wilson SG. Plasma Metabolite Profiles of Children with Autism Spectrum Disorder. Metabolites. 2025; 15(12).

Background/Objectives: Autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social and communication differences, is complex and aetiologically heterogeneous. Untargeted metabolomics is emerging as a tool in screening for biochemical abnormalities. This research was conducted using the Australian Autism Biobank resource and involved analysis of plasma metabolites to characterise metabolite differences between autistic children and controls. Methods: We sought to identify molecular signatures in the plasma of study subjects using mass-spectrometry methods. We included 955 untargeted plasma metabolites from autistic children (n = 491; 2-18 years; 78% male) and control subjects (n = 97; 2-17 years of age; 51% male). Statistical analyses were performed using questionnaire data for both groups, including standardised scores from the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), which measures the severity of autism-related behaviours. We also evaluated intellectual disability by examining the relationships between metabolites and clinical phenotypes. Results: After controlling the false discovery rate at 5%, we identified significant negative associations between the uncharacterised metabolites X-21383 and X-24970 and ASD status (p = 1.85 × 10(-6) and p = 1.92 × 10(-5) respectively). X-21383 was also found to be significantly reduced in autistic children with coexisting intellectual disability when compared with controls (p = 6.06 × 10(-6)). No significant associations were identified between the metabolite data and ADOS-2 scores. However, greater levels of X-16938, N1-methyladenosine, and 2-oxoarginine were found to be suggestively associated with higher ADOS-2 scores (p = 2.95 × 10(-4)-9.6 × 10(-5)). Conclusion: This metabolomics study in the Australian Autism Biobank has identified several novel metabolites associated with core autism diagnostic behaviours.

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13. Romanos-Sirakis E, Javor J. Patterns of emergency department utilization by autistic patients in a large NY health system. Am J Emerg Med. 2025; 101: 7-9.

BACKGROUND: Sensory reactivity and communication challenges can complicate navigating the healthcare system and managing health concerns for autistic individuals. METHODS: Emergency department (ED) encounters for autistic and non-autistic patients from 2023 within 14 hospitals of a large NY healthcare system were evaluated using ICD-10 code F84.0. Outcomes included: percentage of patients accessing care, top primary diagnoses, ED utilization across various ages, admission status, and duration of hospitalization. RESULTS: The study included 711,254 ED visits from 523,057 patients. 1228 patients were documented autistic (0.23 %), which was statistically significantly less than the expected autistic population proportion (p < 0.0001). We found a significant association between age group and autism diagnosis (p < 0.0001), with there being higher proportions of autistic patients in younger age groups. 12.3 % of encounters with autistic patients resulted in admission to the hospital, compared to 23.3 % of the patients without this documented diagnosis (p < 0.0001). The median length of hospitalization for patients with documented autism was shorter (4 days (IQR 2-7)) and 3 days ((IQR 1-6)) (p < 0.0001) for non-autistic and autistic patients, respectively). CONCLUSIONS: In this study, autistic patients utilized the ED at a lower rate than would be expected given the prevalence of autism. The majority of autistic patients seen in the ED were younger (<30 years old). The primary diagnosis varied between autistic and non-autistic patients. Further study is needed to better characterize the challenges seeking care throughout healthcare settings and ensure adequate healthcare supports for the autistic community.

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14. Shen H, Sun X, Wang Z, Jiang M, Wang J, Lu T, Yue W, Zhang D, Wang L, Li J. Common Genetic Variants in TRIO Are Associated With Autism in Chinese Han Population. Genet Res (Camb). 2025; 2025: 7762302.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with high heritability. Nevertheless, the involvement of genetic variants in ASDs is not fully understood. One gene of interest is TRIO, which encodes a large protein that aids in GDP-to-GTP exchange as a Ras homologous (Rho) guanine nucleotide exchange factor (GEF), facilitating cytoskeleton reorganization. Thus, it plays crucial roles in neuronal migration, neurite outgrowth, and synaptic transmission. De novo mutations in TRIO have been extensively reported in the pathogenesis of ASDs. However, no evidence currently supports the genetic association between common variants in TRIO and ASDs. To investigate the role of common genetic variations in autism risk, we analyzed 12 tagging single-nucleotide polymorphisms (SNPs) in the TRIO gene. These tagging SNPs captured an average of 75% of all common variations in TRIO with a minor allele frequency (MAF) > 5%. Using the family-based association study in 239 Chinese Han autism trios, we identified the significant association of three SNPs (rs32593, rs33005, and rs27479) with autism. To confirm the association, the sample size was expanded to 427 trios by recruiting 188 additional trios. Our findings across all 427 trios confirmed that A allele of rs32593, G allele of rs33005, and C allele of rs27479 showed a preferential transmission to the affected offspring (rs32593: A > G, Z = 2.600, p = 0.0093; rs33005: G > T, Z = 2.978, p = 0.0029; rs27479: C > A, Z = 3.214, p = 0.0013) after Bonferroni’s correction (p < 0.0042). Haplotype analyses showed that one haplotype (A-G) constructed from rs32593 and rs33005 was significantly associated with autism (p = 0.0064; Global p = 0.022). These results suggested that the common variants in TRIO might be involved in the susceptibility to autism in the Chinese Han population.

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15. Wolfer P, Tselekidou F, Baumeister F, Gagarina N, Durrleman S. The impact of exposure to additional languages and cognitive factors on narrative macrostructure in autistic and neurotypical children. J Commun Disord. 2025; 119: 106611.

This study adopts a twofold approach to examine how bilingual exposure and (socio-)cognitive factors influence narrative macrostructure in children. First, it investigated the impact of Exposure to Additional Languages (EtAL) on the narrative macrostructure of 90 autistic and 168 neurotypical children (ages 5-12), tested in their most proficient language, either English, French, (Swiss-)German, Italian or Spanish. Macrostructure was assessed through story structure, story complexity, and the production of Internal State Terms (IST), using a series of generalized mixed effects models controlling for age, sex, language skills, and non-verbal IQ. Among neurotypical children, greater EtAL predicted better story structure compared to peers with lower EtAL. No such effect was found in autistic children, suggesting that the potential benefits of EtAL may not extend equally across populations. Additionally, EtAL did not predict story complexity or IST-use in either group. Second, the study investigated the impact of Theory of Mind (ToM), working memory (WM), and metalinguistic awareness (MA) on macrostructure. While ToM and WM showed no significant effects, MA positively predicted story structure across groups. Findings indicate that dimensions of narrative macrostructure may benefit from exposure to multiple languages and MA, especially in neurotypical children. Results further support that, despite advice being provided to families of children with autism to abandon bilingualism, bilingual exposure is not detrimental to the communicative development of autistic children. Leveraging a large, neurodiverse sample and a continuous, hypothesis-driven measure of bilingualism, this study provides generalizable insights into how bilingualism and (socio-)cognitive factors influence narrative development across neurodiverse populations.

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16. Xu T, Zhang Y. Different Supports, Different Effects: Social Support Moderates the Impact of Parenting Stress on the Mental Health of Parents of Individuals with Intellectual and Developmental Disabilities. Eur J Investig Health Psychol Educ. 2025; 15(12).

Parenting stress, social support, and mental health among parents of individuals with intellectual disabilities have garnered significant scholarly attention. Although existing research has extensively elucidated the relationship between parenting stress and mental health, there is limited systematic investigation into the role of social support-particularly regarding which and how social support moderates the impact of parenting stress on the mental health of these parents. Based on data from the 2020 Comprehensive Survey on Caregiving Burden and Public Service Needs of Families with Intellectual Disabilities conducted in Shenzhen, this study examines the relationships among parenting stress, social support, and mental health of Individuals with Intellectual and Developmental Disabilities. The findings reveal that overall, parenting stress exerts a significant negative effect on parental mental health, while social support has a significant positive effect. Further moderation analysis indicates that both subjective support and support utilization partially alleviate the adverse effect of parenting stress on mental health, whereas objective support primarily enhances mental health through a direct pathway. Moreover, differential patterns emerge between parents with and without disabilities: for non-disabled parents, subjective support and support utilization both directly improve mental health and reduce the negative impact of parenting stress. Objective support, however, only contributes directly to mental health and does not show a moderating effect. In contrast, among parents with disabilities, objective support effectively promotes mental health but does not mitigate parenting stress; subjective support and support utilization show neither direct nor buffering effects. These findings enrich the empirical literature on family mental health in the context of intellectual disability and offer practical implications for enhancing family support policies and improving the well-being of affected households.

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17. Yu YY, Wyman A, Faulk CJ, Fulop LJ, Greenberg RL, Benecke RM, Steinbeck LK, Foy J, Kim C, Emory GO, Storch EA, Zampella CJ, Yerys BE, Schultz RT, Parish-Morris J, Herrington JD, Clements CC. An Examination of Racial Bias in Scoring the Autism Diagnostic Observation Schedule (ADOS) Module 3: An Item Response Theory Analysis. Autism Res. 2025.

Given the rising prevalence of autism among racial minority children in the United States, but persistent service use disparities, this study examines potential bias in specific items from the autism diagnostic observation schedule (ADOS), a highly regarded autism evaluation. We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to be rated as showing autistic behaviors than White children with similar autism levels. The impact of racial bias on the item score was small, and the impact on the overall test score was even smaller: on a scale of 0-48 points, the effect of racial bias was estimated at 0.23 total points for Black/African American children and 0.16 points for Asian children. Furthermore, none of the items showing significant bias contribute to the autism classification algorithm. This analysis suggests a small but detectable amount of bias in several specific ADOS items, but not in items central to informing an autism diagnosis. Thus, bias appears statistically, but not clinically, significant. This contributes to examinations of racial bias in the ADOS as the first analysis of Asian children and the first in-depth look at all items in the most commonly used version among school-aged children. In the ADOS, a widely used autism assessment, school‐age children with fluent language who are Asian or Black/African American are slightly more likely to be rated as showing autistic behaviors on 3 out of 24 items. These small differences appear on items that do not affect the total score. Still, clinicians should be aware of possible bias when evaluating Asian and Black/African American children, especially when scoring ADOS Module 3 items A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). eng.

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18. Zhu H, Ye W, Zhou F, Shi L, Zhou Y, Liu P. Global, Regional, and National Burden of Autism Spectrum Disorder: Trends and Decomposition Analysis From 1990 to 2021, and Projections for 2045. Actas Esp Psiquiatr. 2025; 53(6): 1162-75.

BACKGROUND: Autism Spectrum Disorder (ASD) has rising global prevalence and lifelong impacts. We quantified its 1990-2021 burden using Estimated Annual Percent Change (EAPC) trends, decomposition analysis, and the Nordpred model to project burdens to 2045. METHODS: This study analyzed the global, regional, and national ASD burden from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 database, assessing prevalent cases, Disability-Adjusted Life Years (DALYs), Age-Standardized Prevalence Rate (ASPR), and Age-Standardized Disability-Adjusted Life Years Rate (ASDR). It used EAPC to analyze trends, decomposition analysis to examine contributors, and the Nordpred model for predictions to 2045. RESULTS: From 1990 to 2021, prevalent cases rose from 41,929,995.80 to 61,823,539.64, males more affected. ASPR increased from 773.25 to 788.34/100,000, ASDR from 144.51 to 147.56/100,000. The number of DALYs increased by 3.68 million (95 % Uncertainty Interval 3.20-4.10 million) from 1990 to 2021. Middle Socio-demographic Index (SDI) regions saw the largest increases, High SDI regions minimal growth. Among 21 GBD regions, high-income Asia Pacific grew fastest, Oceania declined. Nationally, Japan, South Korea, and Singapore had the highest 2021 ASPR/ASDR, Bangladesh, Brazil, and Nepal the lowest. Decomposition analysis showed population growth drove prevalent cases and DALYs increases, aging caused declines. Predictive models estimate 71,782,946 cases by 2045, DALYs peaking at 13,365,467 years. ASPR and ASDR expected to peak in 2029 (792.16/100,000) and 2034 (148.55/100,000), then decline. CONCLUSION: The rising ASD burden requires immediate action, particularly in middle SDI regions and high-income Asia Pacific, where growth is speeding up. Early intervention and equitable resource distribution for high-risk groups like males and fast-growing populations are essential to cut projected case and DALY increases by 2045.

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