1. Abdel-Ghafar SF, Ahmed AE, Mohammed ET, Abdel-Salam GMH, Abdel-Hamid MS, Zaki MS. EPG5-Related Disorders in Seven New Patients: Refining the Phenotypic Spectrum and Insights on Phenotype-Genotype Correlations. J Mol Neurosci. 2025; 75(4): 147.

Pathogenic variants in EPG5 have been associated with Vici syndrome (OMIM #242840) characterized by agenesis of the corpus callosum (ACC), cataracts, cardiomyopathy, hypopigmentation, and immunodeficiency as hallmark features. Additional variable features include microcephaly, hypotonia, developmental delay, and growth retardation. Recently, few reports described milder cases with a neurodevelopmental phenotype and less systemic involvement harboring EPG5 variants suggesting a broader clinical spectrum. Herein, we describe seven patients from six unrelated Egyptian families in whom exome sequencing identified six homozygous (five novel and one previously reported) EPG5 variants. Patients presented with global developmental delay, microcephaly, hypotonia, dystonia, and failure to thrive. Seizures were evident in two patients and showed a variable response to antiepileptic drugs. Fair color of hair and skin was noted in four out of seven patients (57%), while cataracts and cardiomyopathy were observed in one patient each (14%). In addition to ACC, cerebellar and pontine hypoplasia, delayed myelination, and ventricular dilatation were evident in all patients. Interestingly, deep fissure in the frontal lobes, extending from the frontal horn to the frontal pole, was documented in six patients and appears to represent a characteristic feature associated with EPG5 variants. Our study highlights the phenotypic variability associated with EPG5 variants and emphasizes the presence of a phenotypic spectrum ranging from the classic severe Vici syndrome to a neurodevelopmental disorder with less systemic manifestations and a longer survival rate.

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2. Alehagen L, Hasslinger J, Black MH, Wessman E, Bölte S. Psychometric properties of the operationalized ICF Core Sets for autism and ADHD: item metrics, reliability, and validity. Disabil Rehabil. 2025: 1-28.

PURPOSE: The WHO’s International Classification of Functioning, Disability and Health (ICF) provides a biopsychosocial perspective on health-related functioning, highly relevant for conditions like autism and ADHD. Despite the ICF’s many benefits, including providing a holistic assessment of individual challenges and resources, its widespread use has been prevented by its complexity, lack of operationalization, and limited specificity for certain diagnoses. To improve usability and implementation of the ICF, diagnosis-specific ICF Core Sets have been developed, revised, operationalized, and integrated on a digital platform. This psychometric study evaluates the self-and proxy-report versions of the Core Set operationalization. MATERIALS AND METHODS: This is a cross-sectional study drawing on data collected from individuals diagnosed with autism (n = 54), ADHD (n = 41), autism and ADHD (n = 42), and general population samples (n = 174), as well as 71 paired assessments. RESULTS: Depending on ICF domain, inter-rater reliability and internal consistency was moderate to high. The Core Sets’ ability to distinguish between neurodivergent and general population groups, and the functioning profiles within groups, indicate diagnostic and construct validity. CONCLUSIONS: Findings add psychometric evidence to previous results on feasibility and further endorse the adequacy of the Core Sets operationalization for use in basic and applied autism and ADHD science. Autism and attention deficit-hyperactivity disorder (ADHD) are neurodevelopmental conditions that affect various aspects of functioning; standardized, comprehensive assessments are essential for identifying support needs and guiding clinical practice and research.The ICF CoreSets platform enables structured, person-centered assessment of functioning in autistic individuals and those with ADHD, supporting tailored intervention planning.Psychometric evaluation supports the reliability and validity of the ICF CoreSets platform, reinforcing its clinical utility in clinical contexts.The ICF CoreSets platform can facilitate interdisciplinary collaboration and progress monitoring by providing a standardized framework aligned with WHO’s biopsychosocial model. eng.

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3. Brown SP, Ransdell JL. Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism. J Vis Exp. 2025; (224).

Autism spectrum disorder (ASD) arises from a wide range of genetic and environmental factors. While numerous ASD-linked mutations disrupt synapse development or plasticity, an increasing number have been shown to alter the expression and functioning of voltage-gated ion channels, resulting in deficits in neuronal intrinsic excitability. Whole-cell voltage-clamp recordings can be used to characterize how ASD-related mutations affect ion channel function. However, these experiments fail to directly assess how an altered ionic conductance affects neuronal action potential firing. Dynamic clamp electrophysiology bridges this gap by enabling real-time injection of user-defined ionic conductances into living neurons. This allows causal testing of how changes in ion channel properties affect the electrical activity of a given cell type. In this methods article, we describe how to implement dynamic clamp electrophysiology in adult mouse Purkinje neurons recorded under physiological conditions in acutely prepared cerebellar brain slices. Purkinje neurons are a particularly relevant model for this work because they have an intrinsic capacity to fire repetitive, high-frequency (20-100 Hz) action potentials and are consistently implicated in ASD-related cerebellar circuit dysfunction. We focus on Tsc1, a gene whose loss-of-function mutations are among the most common monogenic causes of ASD. In mouse Purkinje neurons, Tsc1 deletion has also been linked to reduced voltage-gated sodium (Nav) channel expression. We utilize Markov kinetic state models to simulate and reproduce Purkinje neuron Nav conductance properties and go on to use dynamic clamp to directly assess how changes in the Nav conductance impact the intrinsic firing of intact cerebellar Purkinje neurons. We provide instructions and resources for modifying and tuning ionic conductance models. By integrating ionic conductance modeling, dynamic clamp, and conventional patch-clamp techniques, this approach provides a powerful and flexible framework for linking genetic perturbations to physiological outcomes in ASD-relevant neurons.

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4. Chien YL, Chen C, Hsieh MH, Gau SS. Correlation of auditory network hyperconnectivity with P3a amplitude and set-shifting in individuals with autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2025; 143: 111552.

BACKGROUNDS: Individuals with autism spectrum disorder (ASD) exhibit aberrant intrinsic connectivity and altered mismatch negativity responses. Both mismatch negativity and intrinsic connectivity are associated with pre-attentive mechanisms. However, the potential link between mismatch negativity and alterations in intrinsic connectivity in ASD has not been thoroughly explored. This study aimed to investigate the resting-state functional connectivity of the auditory network in ASD and examine its association with mismatch negativity and set-shifting performance. METHODS: This study recruited 75 ASD participants and 50 neurotypical controls (NAC). All participants underwent clinical assessments, mismatch negativity on the oddball paradigm, and resting-state functional MRI. We compared the resting-state brain connectivity of the auditory network between ASD and NAC using independent component analysis. We then examined correlations between this connectivity, mismatch negativity, and executive function measured by the Intra-Extra Dimensional Set Shift task (IED). RESULTS: The ASD group demonstrated resting-state hyperconnectivity between the auditory network and the regions of the posterior cingulate gyrus, left inferior frontal gyrus, right angular gyrus, and right caudate/thalamus. In ASD, the connectivity between the auditory network and the left inferior frontal gyrus was positively correlated with higher P3a amplitude and a greater number of completed stages on the IED task, indicating enhanced cognitive flexibility. CONCLUSION: Findings suggest heightened functional connectivity between the auditory network and various brain regions in ASD. Specifically, connectivity to the left inferior frontal gyrus at rest may predict enhanced attention reorientation and cognitive flexibility in autistic individuals. Further research is warranted to elucidate these relationships.

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5. Chung J, Park EJ, Kim H, Lee A. Group Stepping Stones Triple P for South Korean families of children with developmental disabilities: a pilot study. BMC Res Notes. 2025; 18(1): 463.

BACKGROUND/METHODS: Children with developmental disabilities (DDs) face behavioral, emotional, and social challenges that impact family dynamics. We aimed to investigate the feasibility and effectiveness of the Group Stepping Stones Triple P (SSTP) for South Korean families of children with DDs. Eight parents participated in six online group sessions and three individual phone sessions, supported by a behavior-tracking mobile app. To measure feasibility, satisfaction with the intervention and mobile application, along with participant retention rate, were assessed. Data were collected at three time points to assess behavior problems, quality of life (QoL), parenting stress, efficacy, and parent-child relationships. Wilcoxon signed-rank test was conducted. RESULTS: Participants reported high satisfaction with the intervention and offered suggestions for enhancement. There were no significant improvements between pre- and post-intervention. However, significant improvements in children’s behavior and QoL, parenting efficacy, positive parenting skills, and parent-child relationships were observed at the one-month follow-up. Some individual score change trends were also observed over time. CONCLUSION: This study is the first to conduct Group SSTP in the South Korean context. The results suggest Group SSTP’s potential to address behavioral issues of children with DDs and improve parenting practices, supporting its broader application in healthcare settings.

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

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

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7. Dickerson A, Bond KT. Enhancing Sexual Health Education for Autistic Youth: A Scoping Review of Barriers, Gaps, and Solutions. Am J Sex Educ. 2025.

Autistic adolescents are often excluded from comprehensive sexuality education (CSE) by schools, parents, and healthcare providers, despite growing recognition of their sexual agency. This scoping review examined 42 U.S.- based studies to identify thematic categories that highlight the recurring challenges and opportunities in providing sexuality education for autistic adolescents. Five themes emerged: (1) pervasive misconceptions about autism and sexuality; (2) inadequate access to formal sexual education; (3) parental and clinician discomfort or lack of preparedness to address sexual health; (4) heightened vulnerability to sexual exploitation and adverse health outcomes; and (5) recommendations for inclusive, affirming, and developmentally responsive curricula. Findings highlight how autistic adolescents often receive fragmented, reactive instruction that prioritizes behavior management rather than proactive skill-building in consent, boundaries, and healthy relationships. Evidence suggests that tailored approaches incorporating visual supports, concrete language, and LGBTQ+ inclusivity improve accessibility and relevance. Addressing these gaps requires proper CSE training for autistic adolescents’ family members, teachers, and clinicians to enhance communication, strengthen mutual understanding, and foster more supportive, informed relationships across all parties involved. This review contributes to the growing body of literature that calls for CSE that empowers autistic adolescents to make informed decisions and promotes equitable sexual health outcomes.

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8. Eilon I, Novogrodsky R. The Development of Mental State Verb Use Among Autistic Children. Autism Dev Lang Impair. 2025; 10: 23969415251389127.

BACKGROUND & AIMS: Mental state verbs (MSVs) describe people’s internal states and processes. Reports on the use of MSVs in school-age children with autism spectrum disorder (ASD) are contradictory, and little is known about the developmental trajectories of these verbs in this population during early childhood. In contrast, among young, typically developing (TD) children, research has shown that the use of desire, perception, and physiological verbs precedes the use of cognitive and emotion verbs. This study aimed to describe the development of MSV use among autistic children as compared to TD children and investigate the variables that influence this development. METHODS: A total of 118 children participated in the study (59 autistic and 59 TD children), aged 3-10 years. Parents of all children completed an MSV questionnaire indicating whether their child produced the MSVs included in it. Additionally, two variables influencing MSV use were examined: sentence repetition for estimating syntax and measures of theory of mind (TOM) ability, which included three tasks: diverse desires and first- and second-order false belief. RESULTS: According to the parental questionnaire, cognitive and emotion verbs have a more protracted developmental trajectory in both autistic and TD children than other MSV categories (desire, perception, and physiological verbs), and they are more challenging for autistic children than for TD children. Cognitive and emotion verbs are also less common in preschoolers’ speech than in that of school-aged children. In addition, language abilities, TOM, and group (autistic vs. TD) explained the variance in the development of cognitive and emotion verb use beyond age. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate the development of MSVs from all five semantic categories from the age of three years to the age of ten in autistic children. In addition, our results indicate a specific linguistic difference between autistic and TD children in the development of cognitive and emotion verbs, as was found in the MSV parental questionnaire. The study also highlights the role of syntax, TOM, and autism in relation to the development of these verbs, supporting the notion of complex developmental conditions associated with MSV development and, thus, the need to evaluate them in autistic children.

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9. Féron F, Caillol D, Fourel L, Leimkuhler S, Iranzo O, Gepner B, Guiraudie-Capraz G. An impaired glycolysis induces ATP deficiency and reduced cell respiration in stem cells of patients with autism spectrum disorders. Sci Rep. 2025; 15(1): 38353.

In two previous studies, based on human olfactory ecto-mesenchymal stem cells (OE-MSC) of 11 patients with autism spectrum disorders (ASD) and 11 healthy individuals, we demonstrated that the lower abundance of the enzyme MOCOS (MOlybdenum COfactor Sulfurase) and its associated lower expression of the long non-coding RNA, COSMOC, induces neurotransmission and synaptic defects as well as an exacerbated oxidative stress sensitivity. To move a step further, we assessed whether these defects were associated to a disturbed mitochondrial homeostasis. For that purpose, we used cellular and molecular techniques to quantitfy mitochondrial metabolism and biogenesis, ATP production and cell respiration in OE-MSCs from the 8 ASD patients of the cohort that display the most severe symptoms. We show here that OE-MSCs from ASD patients, when compared to control individuals, display (i) a reduced expression/abundance of glycolysis-associated transcripts and metabolites, (ii) an overall reduced ATP, mainly due to the impaired glycolysis, (iii) a reduced basal cell respiration and (iv) a modified mitochondrial network. These results are in accordance with some of our previously published data and may explain some of the symptoms – stress, overarousal, seizures, increased or decreased muscle tone, fatigue-observed in autism spectrum disorders.

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10. Grosvenor LP, Gunderson EP, Qian Y, Alexeeff S, Ames JL, Weiss LA, Sahagun E, Ashwood P, Yolken R, Zhu Y, Van de Water J, Croen LA. Prenatal Glucose Intolerance and Child Neurodevelopmental Disorders. JAMA Netw Open. 2025; 8(11): e2541657.

IMPORTANCE: Gestational diabetes has been associated with risk of neurodevelopmental disorders (NDD). An improved understanding of this association can inform prevention strategies and elucidate underlying mechanisms. OBJECTIVE: To determine associations between prenatal glucose intolerance and NDD and examine differences by gestational timing and child sex. DESIGN, SETTING, AND PARTICIPANTS: This population-based case-control study examined data from electronic health records from mother-child pairs in an integrated health system in northern California. Children born January 1, 2011, to December 31, 2018, and their mothers were eligible; children were followed up for outcomes through 2023. Data were analyzed from February 2024 to March 2025. EXPOSURES: Gestational diabetes was determined from routine prenatal test results and categorized as diagnosed early (less than 24 weeks), standard (24 to 28 weeks), or late (more than 28 weeks) in gestation. Prenatal subclinical impaired glucose tolerance (IGT) was defined by elevated glucose screening tests and neither GDM diagnosis nor treatment. MAIN OUTCOMES AND MEASURES: Autism spectrum disorder (ASD) and developmental delay were determined from medical records. Adjusted odds ratios (aOR) for associations between prenatal exposures and NDD were estimated using multivariable logistic regression models, adjusted for child sex, birth year, maternal age, race and ethnicity, education, parity, gestational age at prenatal care entry, and prepregnancy body mass index. Effect modification was evaluated by GDM diagnosis timing and sex. RESULTS: A total of 4546 mother-child pairs (median [IQR]) age of diagnosis: ASD, 3.0 [2.0-5.0] years; developmental delay, 2.0 [1.0-3.0] years; 2697 male children [59.3%]) were included in the study, of which 403 mothers (8.9%) had GDM and 64 (1.4%) had IGT; 683 children [15.0%] had ASD, 2054 [45.2%] had developmental delay, and 1809 [39.8%] were controls. GDM was not associated with increased odds of ASD (aOR, 1.15 [95% CI, 0.83-1.60]) or developmental delay (aOR, 1.24 [95% CI, 0.98-1.57]) overall. In sex-stratified analyses, GDM was associated with increased odds of ASD only among females (females: aOR, 2.05 [95% CI, 1.15-3.56]; males: aOR, 0.93 [95% CI, 0.62-1.37]; P for interaction = .04). When assessed by timing, early GDM was associated with increased odds of ASD among females (aOR, 3.23 [95% CI, 1.11-8.91]) but not among males (aOR, 0.78 [95% CI, 0.38-1.56]; P for interaction = .02). There were no associations between standard or late GDM and ASD in either sex. Prenatal IGT was associated with increased odds of developmental delay among females only (females: aOR, 3.25 [95% CI, 1.34-8.68]; males: aOR, 1.07 [95% CI, 0.50-2.39]; P for interaction = .08). CONCLUSIONS AND RELEVANCE: In this case-control study, GDM was associated with NDD in a gestational timing- and sex-specific manner. IGT associations with NDD were also sex-specific, adding to a body of research demonstrating influences of prenatal IGT on child outcomes.

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11. Han Y, Mao C, Zhou K, Liang M, Zhao L, Hong Y, Zhang J, Hu N, Wu F. Fragile X mental retardation 1 gene FMR1 promotes proliferation, migration, and invasion of gastric cancer cells via c-MYC. J Transl Med. 2025; 23(1): 1210.

BACKGROUND: Gastric cancer is a highly aggressive malignancy with poor prognosis and low survival rates. The Fragile X Mental Retardation 1 (FMR1) gene has been implicated in the development and progression of various tumors, but its role in gastric cancer remains unclear. METHODS: We performed pan-cancer expression analysis of FMR1 using the TIMER2.0 platform, and evaluated its differential expression in gastric cancer versus normal gastric tissues in the TCGA cohort. FMR1 expression was validated by qRT-PCR, Western blotting, and immunohistochemistry. Using R software and clinical samples to evaluate the association between FMR1 expression levels and clinicopathological factors in gastric cancer patients, and to analyze patient survival curves. The relationship between FMR1 expression and tumor immune infiltration was analyzed via the TISIDB database, and after co-culture, cytokine secretion by CD4⁺ T cells was assessed using ELISA following FMR1 knockdown in tumor cells. Functional enrichment analyses of FMR1 and its interacting genes were performed. Single-cell transcriptomics was used to extend the interpretation of intratumoral lineages and states. Malignant epithelial populations were identified using inferCNV, and these cells were subsequently stratified by FMR1 expression for GSVA. We measured FMR1 expression in control and FMR1 knockdown gastric cancer cells, performed proliferation, migration, and invasion assays to investigate the biological effects of FMR1 in gastric cancer. Mechanistic insights were further explored through co-immunoprecipitation, cycloheximide chase, proteasome inhibition, and rescue assays. RESULTS: FMR1 was significantly overexpressed in gastric cancer tissues compared to normal gastric mucosa, with high expression levels associated with poor prognosis. The differential expression of FMR1 in gastric cancer was strongly associated with the activity of multiple immune cell types within the tumor microenvironment. Functional assays further demonstrated that FMR1 knockdown suppressed cytokine secretion by CD4⁺ T cells. The expression level of FMR1 in malignant epithelial cells is higher than that in the non-malignant group, and the high-expression group of FMR1 in malignant cells shows a consistent increase in the Hallmark gene sets directly related to stem cell like phenotype, chemotherapy resistance, and immune evasion. Knockdown of FMR1 suppressed gastric cancer cell proliferation, migration, and invasion, while mechanistic studies indicated that FMR1 positively regulates c-MYC expression to drive these phenotypes. And we found that FMR1 interacted with c-MYC at the protein level and stabilized c-MYC by suppressing its proteasomal degradation. CONCLUSION: Our findings demonstrate that FMR1 promotes gastric cancer cell proliferation, migration, and invasion through c-MYC signaling, suggesting that FMR1 may serve as a potential prognostic biomarker and therapeutic target for gastric cancer.

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12. Ingadottir TR, Jonsdottir H, Jarrett MA, Hannesdottir DK. Youth with ADHD, autism or comorbid ADHD and autism in Iceland: Comparisons of attentional and cognitive profiles and the effects of anxiety on cognitive performance. Res Dev Disabil. 2025; 167: 105142.

BACKGROUND: Attentional and cognitive profiles of youth diagnosed with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or co-occurring ADHD and ASD were examined in a large, nationwide clinical sample in Iceland. The impact of anxiety disorders on cognitive performance in this neurodiverse sample was also examined. METHODS: Clinical medical records at a government-run assessment center serving youth from all of Iceland comprised the study sample of 872 youth aged 7-18 years. All participants had been diagnosed with ADHD, ASD, or ADHD+ASD without intellectual impairment; of these, 239 youth were also diagnosed with co-occurring anxiety. All participants completed the Wechsler´s Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Conners Continuous Performance Test 3rd Edition (CPT-3) as part of their diagnostic process. RESULTS: Results indicated that children with ADHD+ASD performed better on the Perceptual Reasoning Index (PRI) on the WISC-IV compared with children with ADHD but showed no difference compared to the ASD only group. On the CPT, differences emerged for children with ADHD, who showed more variability in their performance compared with children with ASD or ADHD+ASD. Children with neurodevelopmental disorders (ADHD and/or ASD) and a co-occurring anxiety disorder performed worse on the Verbal Comprehension Index (VCI) on the WISC-IV. Still, they performed better on the CPT compared with children with neurodevelopmental disorders without anxiety. CONCLUSION: The findings reveal patterns of cognitive performance for children with ASD and/or ADHD with co-occurring anxiety disorders that need to be considered for appropriate accommodation in clinical, teaching and testing approaches for neurodiverse children.

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13. Javadfar Z, Soltani S, Khamoushi F, Sharifi M, Moradi S, Rezaeian S, Foroughi AA, Cheshmeh S, Taghadosi M, Bahrehmand F. Correction: Effect of vitamin D supplementation on inflammatory status and behavioral symptoms in children with autism spectrum disorders: a double-blind randomized clinical trial. BMC Pediatr. 2025; 25(1): 890.

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14. Kianmehr L, MokhtarZadeh K, Yilmaz Z, Darzi Ramandi H, Mehmetbeyoglu Duman E, Funda Sener E, Taheri S, Rassoulzadegan M. DNA/RNA hybrid profiling in autistic patients: A focus on mRNA and non-coding RNA variations. PLoS One. 2025; 20(11): e0326901.

Autism spectrum disorder (ASD) is a set of genetically heterogenous neurodevelopmental disorders characterized by core symptoms including impaired social interaction, communication deficits, and restricted or stereotyped behaviors. While a significant number of cases are not explained by Mendelian inheritance, there is growing evidence for implication of non-coding RNAs (ncRNAs) in the development and inheritance of ASD. Transcriptional studies often face challenges due to patient-specific variations in gene expression and technical differences in preserving RNA integrity. We propose that isolating RNA from DNA/RNA hybrids provides a robust method to reliably capture transcriptional information. We performed a whole transcriptome analysis on blood samples from ASD patients and healthy controls to investigate transcripts associated with DNA/RNA hybrids. We identified 278,300 novel transcripts across 68,487 DNA/RNA hybrid loci, with significant enrichment in exonic and intronic regions. The novel long non-coding RNAs (lncRNAs) we found showed higher expression levels compared to known transcripts. Differential expression analysis revealed 301 significantly upregulated and 401 downregulated known transcripts in ASD samples compared to controls (|log2-fold change| > 1 and adjusted p-value < 0.05). Through qRT-PCR validation, we confirmed the significant upregulation of RN7SK and SMARCC2 associated with DNA/RNA hybrids in ASD patients. Pathway and enrichment analyses highlighted mitochondrial dysfunction and energy metabolism. Our results suggest that ncRNAs can form DNA/RNA hybrids that influence gene expression, providing preliminary insights into the mechanisms of transcriptional dysregulation in ASD.

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15. Kim JI, Lee DW, Lee YJ, Lee YA, Shin CH, Hong YC, Kim BN, Lim YH. Prenatal exposure to heavy metals and the trajectory of autistic traits in childhood. Environ Res. 2025; 288(Pt 1): 123269.

BACKGROUND: The association between prenatal heavy-metal exposure and autistic traits remains underexplored. OBJECTIVES: This study aims to investigate the association between prenatal heavy-metal exposure and autistic traits in offspring, and their trajectories during childhood. METHODS: In a prospective birth cohort of 540 mother-child pairs, we measured maternal blood levels of lead, cadmium, mercury, and manganese during the second trimester. Autistic traits were assessed at ages 4, 6, 8, and 10 years, and trajectories were identified using latent class growth modeling. Regression models examined associations between individual and mixture effects of prenatal heavy-metal exposure and autistic traits at each age, as well as their trajectories (low vs. high score classes). RESULTS: Prenatal lead exposure was significantly associated with autistic traits at 8 years (15.8 % increase per doubling; 95 % confidence interval [CI], 2.1-31.4). In girls, prenatal lead exposure was associated with autistic traits at 6 (46.4 % increase; 95 % CI, 19.0-80.1), 8 (57.9 % increase; 95 % CI, 26.0-98.0), and 10 (32.3 % increase; 95 % CI, 5.8-65.4) years. Prenatal lead exposure was associated with trajectory class only in girls, with an odds ratio (OR) of 2.7 (95 % CI, 1.0-6.9) for belonging to the high-score class per doubling of exposure. Maternal heavy-metal mixtures were marginally associated with autistic trait trajectories. CONCLUSION: This is the first study to link prenatal heavy-metal exposure with autistic trait trajectories. Prenatal lead exposure showed consistent associations across multiple childhood stages in girls, highlighting the need to reduce prenatal exposure and to consider sex-specific developmental pathways in neurodevelopmental research.

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16. Lin D, Shi Z, Hao Z, Xie X, Fang J, Li M, Zhang W, Luo S, Xue A. Global burden, inequality, and frontier gaps of autism spectrum disorder disability in adolescents and young adults, 1990-2021: a systematic analysis of the GBD 2021 study. Front Public Health. 2025; 13: 1681565.

BACKGROUND: Autism spectrum disorder (ASD) ranks among the leading causes of years lived with disability in adolescence and young adulthood (AYA), yet global assessments still focus on childhood and seldom examine how national development modifies burden. METHODS: We analysed Global Burden of Disease 2021 data for 204 countries and territories from 1990 to 2021. Among AYA aged 15-39 years, we extracted the age-standardised prevalence rate (ASPR) and disability-adjusted life-year rate (ASDR), stratified by sex, five-year age groups and Sociodemographic Index (SDI) quintile. Temporal trends were evaluated using the Estimated Annual Percentage Change (EAPC). Cross-country absolute and relative inequalities were quantified with the Slope Index of Inequality (SII) and Concentration Index (CIX). A half-normal stochastic frontier model defined the minimum attainable ASDR for each SDI level; country-year gaps were calculated as observed minus frontier values. RESULTS: From 1990 to 2021, prevalent ASD cases increased from 17.52 to 24.13 million and DALYs from 3.30 to 4.55 million. Despite higher counts, global age-standardised rates changed little: in 2021 the ASPR was 811.67 per 100000 (95% UI 683.34-952.87) and ASDR 153.00 (95% UI 103.77-215.64); EAPCs were near zero. Males contributed about two-thirds of the burden (rate ratio ≈2.1). Disability rose most at ages 30-39 (+56%). A persistent SDI gradient was observed: high-SDI settings recorded ASPR 1090.72 and ASDR 205.00 versus 845.15 and 158.57 in low-SDI settings. In 2021, SII was 22.53 (95% UI 12.53-32.53) and CIX 0.04 (95% UI 0.02-0.05). Several high-income economies exceeded the frontier, while Bangladesh, Somalia and Niger lay on or below it-likely reflecting surveillance gaps rather than low burden. CONCLUSION: Absolute ASD disability in AYA has risen mainly from population growth and case detection, not higher per capita risk. A sustained male predominance, a renewed peak at ages 30-39, and minimal progress on inequality show that economic gains alone have not reduced burden. Expanding adult screening, vocational support and community-based interventions, alongside stronger surveillance and parent training in low-SDI settings, is required to narrow global gaps.

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17. Moseley RL, Marsden SJ, Allison CL, Parsons TA, Cassidy S, Procyshyn T, Pelton M, Weir EM, Chikaura T, Mosse D, Hall I, Owens L, Cheyette J, Crichton D, Rodgers J, Hodges H, Baron-Cohen S. « A combination of everything »: a mixed-methods approach to the factors which autistic people consider important in suicidality. Autism Adulthood. 2025.

BACKGROUND: Suicide is a leading cause of death for autistic people, but inadequately explained by theories derived in non-autistic populations. Autistic people’s perceptions of the factors underpinning suicidal experiences are vital for guiding conceptual understanding, risk assessment, and policy and clinical practice towards preventing suicide. METHODS: We recruited 1369 autistic participants for an online survey designed through consultation with autistic people. Participants were 326 cisgender men, 718 cisgender women, and 325 transgender or gender-divergent individuals, ranging from 16-89 years old. We asked them to rate the importance of 19 contributing factors to their suicidal thoughts and feelings, and enter their own explanations of additional factors if desired. Alongside thematically analysing this qualitative data, we examined whether ratings of contributing factors differed by age and gender, and whether ratings statistically predicted levels of lifetime suicidality. RESULTS: Loneliness, feelings of worthlessness/failure, hopelessness and mental illness were the highest rated contributing factors to suicidal thoughts and feelings, particularly by autistic women and sex/gender minorities; ratings also differed by age. Qualitative responses indicated the complexity of suicidality, wherein autistic status influenced both the nature of the stressors (e.g. societal stigma) and cognitive-emotional states (e.g. feeling disconnected through feeling different to others) that participants identified. Greater perceived importance of bullying, difficulties accessing support and past trauma characterised participants with experience of suicide plans or attempts. CONCLUSION: While some of the experiences and mental states identified by participants resembled those identified in non-autistic groups, the psychological profile of autistic participants and their experiences of marginalisation appeared to heavily contextualise expressions of hopelessness, burdensomeness, worthlessness, loneliness and entrapment. Autistic people vary with regards the factors perceived to underpin suicidality. However, associations between suicidality and the perceived importance of bullying, trauma, and inability to access support highlight the necessity of societal and systemic change to prevent suicide.

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18. Paranjapye A, Ahmad R, Su S, Waldman AJ, Phillips-Cremins JE, Zhang S, Korb E. Autism spectrum disorder risk genes have convergent effects on transcription and neuronal firing patterns in primary neurons. Genome Res. 2025; 35(11): 2433-44.

Autism spectrum disorder (ASD) is a highly heterogenous neurodevelopmental disorder with numerous genetic risk factors. Notably, a disproportionate number of risk genes encode transcription regulators including transcription factors and proteins that regulate chromatin. Here, we test the function of nine such ASD-linked transcription regulators by depleting them in primary cultured neurons. We then define the resulting gene expression disruptions using RNA sequencing and test effects on neuronal firing using multielectrode array recordings. We identify shared gene expression signatures across many ASD risk genes that converge on the disruption of critical synaptic genes. Fitting with this, we detect robust disruptions to neuronal firing throughout neuronal maturation. Together, these findings provide evidence that the loss of multiple ASD-linked transcriptional regulators disrupts transcription of synaptic genes and has convergent effects on neuronal firing that may contribute to enhanced ASD risk.

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19. Petersson-Bloom L, Hansson E. A Systematic Research Review on Teachers’ Self-Efficacy in Educating Autistic Students. Autism Dev Lang Impair. 2025; 10: 23969415251392318.

BACKGROUND AND AIM: Ensuring equitable education for all students, including those with autism, is a core international commitment. The OECD (2018) defines equitable education as providing equal learning opportunities through responsive support tailored to individual needs. From this perspective, inclusive education involves both rights-based and needs-based approaches and emphasizes the importance of quality and adaptability in educational provision. Teachers’ self-efficacy-their perceived confidence and belief in their ability to teach and support autistic students-is a critical factor in achieving these aims. However, despite growing commitments to inclusion, challenges are frequently reported not only by teachers, but also by parents and autistic students, including feelings of exclusion, misunderstanding, and inadequate support within educational settings. This review aims to synthesize existing research on teachers’ self-efficacy in educating autistic students, identify influencing factors, assess methodological approaches, and outline future directions. METHODS: A mixed-methods systematic review was conducted using a convergent integrated design. Qualitative, quantitative, and mixed-methods studies were synthesized. Searches were carried out in four databases: PsycInfo, ERIC, Education Source, and SCOPUS. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT; Hong et al., 2018), and the review followed PRISMA guidelines. MAIN CONTRIBUTION: Fifty-seven studies were included. Findings indicate that although many teachers are willing to support autistic students, their self-efficacy is often undermined by limited professional development, structural barriers, and insufficient support. Key facilitators include sustained, practice-oriented professional development and supportive leadership. However, the predominance of self-report methods limits understanding of how self-efficacy translates into classroom practice. CONCLUSIONS: Teacher self-efficacy is shaped by both systemic conditions and individual perceptions of the ability to meet diverse student needs. Strengthening self-efficacy is essential to advancing equitable education for autistic students.

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20. Pollali E, Donaire DF, Ángel MD, Demiray YE, Lacalle SE, Hollnagel JO, Annamneedi A, Çalışkan G. Aberrant hippocampal gamma oscillations in a mouse model of fragile X syndrome: insights from in vitro slice models. Mol Autism. 2025; 16(1): 55.

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by the loss of fragile X mental retardation protein (FMRP), which regulates neuronal signaling and plasticity. FXS patients and Fmr1 knockout (KO) mice exhibit sensory hypersensitivity, hyperarousal, and hippocampus-dependent learning deficits. Dysregulated metabotropic glutamate receptor (mGluR) and muscarinic acetylcholine receptor (mAChR) signaling, along with reduced kainate receptor (KAR) function, have been implicated in FXS pathophysiology. Activation of these signaling pathways induce gamma-frequency network oscillations hippocampal slices in vitro. However, their specific contribution to aberrant gamma oscillations in FXS remains unclear. METHODS: We recorded local field potential (LFP) gamma oscillations in vitro in hippocampal CA3 from wild-type (WT) and Fmr1 KO mice. Oscillations were induced pharmacologically using carbachol (CCh), the group I mGluR agonist dihydroxyphenylglycine (DHPG), or kainate (KA). In addition, we quantified synaptic protein expression of mAChR M1, mGluR1, mGluR5, GluK1, and GluK2-receptors involved in gamma oscillation generation under these conditions. RESULTS: Fmr1 KO slices exhibited increased integrated gamma power (20-80 Hz) in response to DHPG and CCh, suggesting higher network synchronization through mGluR and mAChR pathways. In contrast, KA-induced oscillations showed reduced synchrony and gamma peak power, indicating disrupted network coordination. Aberrant spiking activity during both CCh- and KA-induced oscillations further supports impaired temporal coordination in Fmr1 KO mice. These physiological changes were only partially reflected by altered expression of the corresponding receptor proteins. LIMITATIONS: In the current study, we found aberrant gamma oscillation power in in vitro hippocampal slices of Fmr1 KO mice. It remains to be determined whether these oscillatory changes extend to pharmacologically induced gamma oscillations in cortical slice preparations in vitro. CONCLUSIONS: Our findings demonstrate that hippocampal gamma oscillations are differentially affected by distinct neuromodulatory pathways in Fmr1 KO mice. Enhanced responsiveness to cholinergic and mGluR activation and reduced coherence of KA-induced rhythms suggest that multiple dysregulated mechanisms contribute to gamma oscillopathies in FXS.

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21. Roberts E, Francesconi M, Flouri E. The relationship between childhood autistic traits and diurnal cortisol activity in adolescence. Psychoneuroendocrinology. 2025; 183: 107672.

BACKGROUND: Autistic adolescents experience higher levels of stress compared to non-autistic adolescents. Chronic stress is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which can be measured by cortisol levels. Previous studies investigating cortisol activity in autistic adolescents are predominantly cross-sectional, have small sample sizes, exclude females, and include those with a clinical diagnosis of autism. The currently study sought to prospectively examine whether the severity and persistence of autistic traits in childhood is associated with cortisol activity in adolescence in a population-representative cohort. METHODS: Data from 915 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used. Bivariate correlations were calculated between autistic traits (using the Social Communication Disorders Checklist) at ages 8, 11 and 14 years and four cortisol activity indices at age 15 years (diurnal cortisol slope, cortisol awakening response (CAR), total morning cortisol, and daily total cortisol output). Regression analyses investigated the effect of autistic traits on cortisol activity, before and after adjustment for confounders. RESULTS: Being likely autistic (i.e., demonstrating severe and persistent autistic traits across ages 8-14 years) was associated with increased CAR, even after adjustment for confounders. No associations were observed between autistic traits and diurnal cortisol slope, total morning cortisol, or total daily cortisol output. CONCLUSION: The observation that autistic traits are associated with CAR, but not other cortisol activity indicators, suggests this may not reflect a generalised HPA axis dysfunction in autistic youth, but a heightened situational response during periods of transition and increased anticipatory stress.

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

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

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23. Shields G, Rowlandson A, Davies L, Leadbitter K, Smallman R, Langhorne S, Chu P, Emsley R, Bee P, Hackett L, Dunkerley A, Harrison L, Ellis C, Hutton T, Butter C, Goldie C, James K, Green J. A post-diagnostic psycho-education, acceptance and commitment therapy programme for caregivers of children recently diagnosed with autism: a randomised controlled trial-based cost-effectiveness analysis (REACH-ASD Trial). EClinicalMedicine. 2025; 88: 103470.

BACKGROUND: Caregivers of autistic children experience higher rates of mental health difficulties, caregiving complexities, and employment challenges, resulting in reduced health status and productivity losses. We evaluated the cost-effectiveness of a group psychosocial intervention (Empower-Autism) plus treatment as usual (TAU), in comparison to TAU alone, for caregivers of children recently diagnosed with ASD. METHODS: A multicentre, assessor-masked, randomised controlled trial of 379 primary caregivers of children with a recent ASD diagnosis in North-West England prospectively collected economic data. The trial (ISRCTN 45412843) was prospectively registered on Sept 11, 2019 and participants were referred and screened for inclusion between Sept 16, 2020 and April 14, 2022. The final data extract was performed on Aug 31, 2023. The primary outcome of the cost-effectiveness analysis was quality-adjusted life years (QALYs) at 52-week follow-up. Missing data were imputed using multiple imputation. Uncertainty was explored by probabilistic bootstrapping. Sensitivity analyses tested the impact of study design and assumptions on the incremental cost-effectiveness ratio (ICER). FINDINGS: Primary (imputed data) and complete case analyses have contrasting results; the complete case suggests the intervention may be cost-effective (net cost £786; net QALY 0.049; ICER ∼£16 k) in contrast to the primary analysis (net cost £756; net QALY 0.015; ICER ∼£51 k). Using the GHQ-30 (trial primary outcome, measuring mental health) as an alternative measure of benefit resulted in a cost of £150 per point improvement (statistically significant health gain, clinically meaningful at ∼£750/individual). INTERPRETATION: The proportion of participants with incomplete data, likely in part due to the COVID-19 pandemic, results in uncertainty. However, there is some indication that the intervention is cost-effective. Further research is needed to explore the potential longer-term cost-effectiveness of Empower-Autism. FUNDING: NIHRHTA Programme (17/80/09).

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24. Solek P, Gamayani U, Rusmil K, Afriandi I, Prasetya T, Rizqiamuti AF, Nurfitri E, Burhan, Sahril I, Gunawan K. Behavioral and pharmacological intervention in autism spectrum disorder: CARS score changes across cognitive levels. Tzu Chi Med J. 2025; 37(4): 444-51.

OBJECTIVES: This study aimed to investigate the core symptom of autism in Indonesian children using Childhood Autism Rating Scale (CARS) scores and their relationship with cognitive profiles while evaluating the effectiveness of aripiprazole and behavioral intervention across different cognitive levels. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was conducted in Bandung City, Indonesia, from February 2023 to January 2024. Participants aged 6-10 years with autism spectrum disorder (ASD) were assessed using CARS and Stanford-Binet Intelligence Scales Form L-M. They were randomized to receive either aripiprazole with behavioral therapy (BT) or placebo with BT for 12 weeks. CARS scores and cognitive levels were evaluated at baseline and after treatment. RESULTS: The study enrolled 51 participants (29 placebo and 22 aripiprazole). Both groups showed significant improvements in CARS and cognitive scores over 12 weeks. The aripiprazole group demonstrated greater reductions in CARS scores (5.17 points for higher-cognitive level [HC-ASD]; 4.88 points for lower-cognitive level [LC-ASD] compared to the placebo group. Significant improvements were observed in visual response, taste/smell/touch response, and fear/nervousness CARS subcategories (P < 0.05). Receiver operating characteristic analysis revealed that CARS scores at end-of-treatment (EoT) were strong predictors of cognitive improvement, with an optimal cutoff of 36.25 achieving high sensitivity and specificity (AUC 0.776, P < 0.05). CONCLUSION: Early identification, accurate differentiation between LC-ASD and HC-ASD, and targeted interventions combining pharmacological treatment with BT are essential for improving outcomes in children with ASD. These approaches can reduce symptom complexity while fostering long-term functional skills development.

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25. Suthar S, Sethi S. Coping strategies for stress in parents of children with autism spectrum disorder: A cross-sectional study from North India. Ind Psychiatry J. 2025; 34(3): 396-401.

BACKGROUND: Autism spectrum disorder (ASD), a lifelong neurodevelopmental condition, often imposes significant psychological stress on parents. Identifying parental coping mechanisms is essential for addressing their needs and improving mental health. AIM: To explore coping strategies and their impact on parental stress. MATERIALS AND METHODS: This cross-sectional study involved 45 children diagnosed with ASD and their parents, all of whom were attending the Child and Adolescent Guidance Clinic at Tertiary care centre in Haryana. The severity of ASD in children was assessed using the Childhood Autism Rating Scale (CARS). Parental stress levels were evaluated using the stress subscale of Hindi version of the Depression Anxiety Stress Scales (DASS). The Stress Coping Behaviour Scale (SCBS) was used to assess parental coping strategies. RESULTS: The results indicated that 58% of parents experienced mild stress, with mothers reporting significantly higher stress levels than fathers. A significant association was observed between the levels of parental stress and the types of coping strategies employed. Most parents predominantly used adaptive coping mechanisms such as active coping, emotional support, planning, acceptance, and religious practices, while maladaptive strategies were less commonly adopted. CONCLUSION: The study reveals that parental stress levels positively correlate with maladaptive coping strategies and negatively correlated with adaptive ones. It addresses a research gap by exploring coping strategies among parents of children with ASD in India, a context largely overlooked in Western-focused studies.

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26. Turfa M, Rida A, Siblany Y, Ramadan F, Madhoun Y, Mohammed A, Turfa M, Wehbe D, Zaylaa M. Autism spectrum disorder knowledge among kindergarten teachers in Lebanon: a cross-sectional survey. BMJ Paediatr Open. 2025; 9(1).

BACKGROUND: Autism spectrum disorder (ASD) is defined by persistent social communication difficulties and restricted, repetitive behaviours. Its increasing prevalence heightens the demand for earlier diagnosis and intervention. ASD can be diagnosed between 18 and 24 months, the typical kindergarten entry age, highlighting the vital role of kindergarten teachers in early detection. In Lebanon, the economic crisis has increased the demand for kindergarten services as both parents are working. This study aims to assess the knowledge of kindergarten teachers in Lebanon about ASD, emphasising their role in early detection and intervention referral. METHODS: A descriptive cross-sectional study was conducted between June 2023 and January 2024 using convenience sampling. Data were collected through a survey administered to 355 kindergarten teachers from all Lebanese governorates. The questionnaire assessed participants’ sociodemographic characteristics, perceived knowledge of ASD and included the validated Autism Spectrum Knowledge Scale-General. RESULTS: Responses were obtained from 355 kindergarten teachers, aged 18 to 50 years, representing 57 kindergartens. Overall, Lebanese kindergarten teachers demonstrated moderate knowledge of ASD, with a mean score of 17.7/32 (55.3%). The level of knowledge regarding the symptoms and associated behaviours, assessment and diagnosis, treatment, outcomes and prognosis of the disease was moderate (59.9%, 58.2%, 54.3% and 52%, respectively). The lowest scores were observed in items related to the aetiology and prevalence of ASD (48.3%). Moreover, areas of residence, years of experience, sources of information and prior interactions with children with ASD were all statistically significant predictors of ASD knowledge (p=0.046, p=0.002, p=0.043 and p<0.001, respectively). Multivariate linear regression revealed that area of residence (p=0.009) and prior interaction with children with ASD (p<0.001) were significantly associated with knowledge scores. CONCLUSIONS: Many teachers are unfamiliar with ASD and its implications for children, yet it is crucial to raise awareness of ASD and incorporate it into educational curricula.

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27. Vasconcelos MM, Vasconcelos LGA, Brito AR. Unveiling autism spectrum disorder for the pediatrician. J Pediatr (Rio J). 2025; 102 Suppl 1(Suppl 1): 101458.

OBJECTIVES: To review the state of the art in autism spectrum disorder (ASD), including its etiologic puzzle, clinical features, pathophysiologic mechanisms, differential diagnosis, and therapeutic management. DATA SOURCES: A search for papers published over the past 10 years in the databases PubMed-MEDLINE, Cochrane Library, and SCIELO was performed using the following terms: « autism » and « clinical features », « differential diagnosis », « pathophysiology », or « management ». The search yielded 3240, 590, 6904, and 5023 papers, respectively. A total of 120 most relevant papers were selected based on their title and abstract content. DATA SYNTHESIS: The current prevalence of ASD is 1 in every 31 eight-year-old children. A genetic defect is found in 10-20% of individuals with ASD. Environmental risk factors that increase the likelihood of ASD include advanced parental age and maternal health conditions. Epigenetic mechanisms may play a crucial role in the interplay between genetic and environmental factors in the pathogenesis of ASD. In addition to language delay, pediatricians should monitor and screen for several early signs of ASD. Differential diagnosis is complex because several neurodevelopmental conditions show clinical features that overlap with ASD. Medications may be used to treat comorbid conditions. CONCLUSIONS: Management is based on a multidisciplinary team, and pediatricians are in a unique position to coordinate this team, given the trustworthy relationship they have with patients and their families.

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28. Vicioso C, Alon N, Adler MJ, Schlachte B, Kolevzon A, Ranade SC. A Medical Student’s Reflections on Autism, Movement, and Orthopaedic Collaboration: Beyond the Clinic. J Bone Joint Surg Am. 2025.

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29. Vidya S, Gupta K, Aly A, Wills A, Ifeachor E, Shankar R. Identification of critical brain regions for autism diagnosis from fMRI data using explainable AI: an observational analysis of the ABIDE dataset. EClinicalMedicine. 2025; 88: 103452.

BACKGROUND: Diagnosis of autism spectrum disorder (ASD) significantly improves quality of life, yet current diagnostic practices rely on subjective behavioural assessments. While machine learning models using functional Magnetic Resonance Imaging (fMRI) show promise for objective diagnosis, existing approaches have critical limitations. High-accuracy models often neglect interpretability, increasing clinical distrust, while interpretable approaches frequently suffer from low accuracy and lack neuroscientific validation of identified biomarkers. Furthermore, no studies have systematically benchmarked which interpretability methods are most effective for fMRI data, hindering the translation of Artificial intelligence (AI) findings into clinical practice. METHODS: In this observational study, we used the Autism Brain Imaging Data Exchange I (ABIDE I) dataset comprising 884 participants (408 with ASD; 476 controls with typical development) aged 7-64 years from five countries (Belgium, Germany, Ireland, the Netherlands, and the USA) across 17 international sites after applying mean framewise displacement (FD) filtering (>0.2 mm). Data were collected at the respective sites prior to the release of the ABIDE I dataset in August 2012. We described an explainable deep learning (DL) pipeline using a Stacked Sparse Autoencoder (SSAE) with a softmax classifier, trained on functional connectivity data. We systematically benchmarked seven interpretability methods using the Remove And Retrain (ROAR) technique and cross-validated our findings across three preprocessing pipelines. Critically, we validated identified biomarkers against independent neuroscientific literature from genetic, neuroanatomical, and functional studies. FINDINGS: Filtering head movement (FD > 0.2 mm) increased classification accuracy from 91% to 98.2% (F1-score: 0.97), achieving state-of-the-art performance. ROAR analysis revealed gradient-based methods, particularly Integrated Gradients, as most reliable for fMRI interpretation. The model consistently identified visual processing regions (calcarine sulcus, cuneus) as critical for ASD classification. These findings aligned with independent genetic studies and neuroimaging research, confirming our model captured genuine neurobiological ASD markers rather than overfitting to dataset artifacts. INTERPRETATION: We addressed three key research gaps by developing a highly accurate, interpretable ASD classification model, establishing a benchmarking framework for interpretability methods in the fMRI modality, and validating our identified biomarkers against established neuroscience literature. The consistent importance of visual processing regions suggests a fundamental biomarker potentially present across the ASD spectrum, offering new directions for diagnostic biomarker research, though translation to individual-level clinical applications requires further development. FUNDING: This work was supported by the Engineering and Physical Sciences Research Council, UK [EP/W524554/1].

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30. Wang L, Meng H, Meng Z, Wang Y, Wong PCM. A systematic review and meta-analysis of autism screening and diagnosis in children using video-assisted telehealth technology. Digit Health. 2025; 11: 20552076251386705.

OBJECTIVE: Early support and intervention for autism have proven effective in improving developmental outcomes. However, the heterogeneity of the condition, coupled with the scarcity and uneven distribution of medical resources, presents significant challenges for early detection. Telehealth, particularly through video-based behavioral observation, has shown considerable potential in expediting the autism diagnostic pathway. This systematic review and meta-analysis aimed to evaluate the accuracy of video-assisted telehealth technologies for autism screening and diagnosis, and to assess whether function (screening vs. diagnosis) and category (video conferencing, video recording, or machine learning using short videos) influence effectiveness. METHODS: This review followed PRISMA guidelines and was registered on PROSPERO (CRD42022376674). A systematic search was conducted for studies published up to November 20, 2024. After screening, 41 studies met inclusion criteria. Meta-analytic procedures were applied to calculate sensitivity and specificity. Subgroup analyses were conducted to compare performance by function and category. RESULTS: Across studies, the pooled sensitivity was 0.88 (95% confidence interval (CI): 0.84-0.91) and specificity was 0.76 (95% CI: 0.72-0.80), indicating good sensitivity and moderate specificity for autism detection. Subgroup analysis showed that diagnostic datasets performed better than screening datasets in both sensitivity and specificity. Furthermore, machine-learning technologies demonstrated the highest sensitivity and specificity compared to video conferencing and video recording. CONCLUSION: Video-assisted telehealth technologies demonstrate strong potential for enhancing early autism detection. However, existing evidence remains preliminary, with studies predominantly conducted in the United States. Future research should prioritize validating these tools in geographically and demographically diverse populations, including low- and middle-income regions.

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31. Witwer AN, Wallace JN. Editorial: Persistent Challenges in Addressing the Mental Health Needs of Autistic People and a Suggested Way Forward. J Am Acad Child Adolesc Psychiatry. 2025.

It is well documented that autistic people are at an increased risk for co-occurring mental health challenges and suicide.(1) There is also a robust and ever-growing body of literature delineating the challenges of meeting the varied mental health needs of autistic children, adolescents, and adults-most notably, access to efficacious treatments. For those who are able to access services, there are concerns about ableism and the failure of clinicians to understand how autistic characteristics may interact with mental health presentation and treatment response. Access difficulties are exacerbated by the general lack of disability- and autism-related content in curricula of preprofessional programs, resulting in a workforce who report being ill prepared to work with this population.(2,3) It is imperative to have evidence-based mental health treatments. Equally important is the method by which such treatments are developed, studied, and disseminated. The autism community has identified key considerations for researchers who study treatment development, implementation, and dissemination.(4,5) Most notable is the inclusion of and collaboration with autistic people, from all stages of research, treatment conceptualization through dissemination, and examining outcomes that matter to them. The emergence of rigorous randomized controlled trials (RCTs) such as those by White et al.(6) are a strong step forward in addressing issues about efficacious treatment, as well as inclusion of the autistic community. As such, the White et al.(6) study can serve as a model for others. Furthermore, the research community needs to diversify the composition of study participants, and as a field we need to turn more focus toward dissemination and training, both of which are imperative for improving access.

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32. Yazdanbakhsh A, Dang KTM, Kuang K, Lian T, Liu X, Xie S, Zikopoulos B. Artificial Intelligence Networks Combining Histopathology and Machine Learning Can Extract Axon Pathology in Autism Spectrum Disorder. Autism Res. 2025.

Axon features that underlie the structural and functional organization of cortical pathways have distinct patterns in the brains of neurotypical controls (CTR) compared to individuals with Autism Spectrum Disorder (ASD). However, detailed axon study demands labor-intensive surveys and time-consuming analysis of microscopic sections from postmortem human brain tissue, making it challenging to systematically examine large regions of the brain. To address these challenges, we developed an approach that uses machine learning to automatically classify microscopic sections from ASD and CTR brains, while also considering different white matter regions: superficial white matter (SWM), which contains a majority of axons that connect nearby cortical areas, and deep white matter (DWM), which is comprised exclusively of axons that participate in long-range pathways. The result was a deep neural network that can successfully classify the white matter below the anterior cingulate cortex (ACC) of ASD and CTR groups with 98% accuracy, while also distinguishing between DWM and SWM pathway composition with high average accuracy, up to 80%. Examination of image regions important for network classification and misclassification, through sensitivity maps, along with multidimensional scaling analysis, helped identify key pathological markers of ASD and highlighted the spectrum of ASD heterogeneity and overlaps with neurotypical characteristics. Large datasets that can be used to expand training, validation, and testing of this network have the potential to automate high-resolution microscopic analysis of postmortem brain tissue, so that it can be used to systematically study white matter across brain regions in health and disease.

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