1. Bae S, Hong J, Ha S, Moon J, Yu J, Choi H, Lee J, Do R, Sim H, Kim H, Lim H, Park MH, Ko E, Yang CM, Lee D, Yoo H, Lee Y, Bong G, Kim JI, Sung H, Kim HW, Jung E, Chung S, Son JW, Yoo JH, Jeon S, Kim H, Kim BN, Cheon KA. Multimodal AI for risk stratification in autism spectrum disorder: integrating voice and screening tools. NPJ Digit Med. 2025; 8(1): 538.

Early Autism Spectrum Disorder (ASD) identification is crucial but resource-intensive. This study evaluated a novel two-stage multimodal AI framework for scalable ASD screening using data from 1242 children (18-48 months). A mobile application collected parent-child interaction audio and screening tool data (MCHAT, SCQ-L, SRS). Stage 1 differentiated typically developing from high-risk/ASD children, integrating MCHAT/SCQ-L text with audio features (AUROC 0.942). Stage 2 distinguished high-risk from ASD children by combining task success data with SRS text (AUROC 0.914, Accuracy 0.852). The model’s predicted risk categories strongly agreed with gold-standard ADOS-2 assessments (79.59% accuracy) and correlated significantly (Pearson r = 0.830, p < 0.001). Leveraging mobile data and deep learning, this framework demonstrates potential for accurate, scalable early ASD screening and risk stratification, supporting timely interventions.

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2. Bajaj S, Gandhi S, Geetha TS, Venkata M, Chitre A, Sagi N, Agrawal N, Shah S, Deo R, Pai S, Jacob KS, Murugan S, Menon R, Gupta R, Athota JP, Mali V, Phani NM, Sengupta K, Mehta P, Udani V, Bassi A, Charugulla S, Gadgil P, Vedam R, Hegde AU. Prospective study to analyze the yield and clinical impact of trio exome sequencing in 137 Indian children with autism spectrum disorder. J Hum Genet. 2025.

We aimed to study the diagnostic yield and clinical impact of trio exome sequencing (tES) in children with autism spectrum disorder (ASD). Participants (n = 137) between 2 and 18 years with syndromic and non-syndromic ASD underwent tES, after excluding karyotype-detectable cytogenetic abnormalities and fragile X syndrome. The diagnostic yield was 22/137 (16.1%) when considering only pathogenic (P) and likely-pathogenic (LP) variants in known disease-causing genes. We reported 23 significant (P, LP) variants in 22 individuals, with one participant (AGS041) harbouring a dual genetic diagnosis. Nearly half of these (12/23, 52.2%) were novel, while 21/23 (91.3%) occurred de novo. 20/23 (86.9%) of the variants were single nucleotide variants, while 3/23 (13.1%) were copy number variants. The diagnostic yield in syndromic ASD (14/40, 35%) was significantly higher than the non-syndromic group (8/97, 8.2%, p = 0.000258). Variants of uncertain significance in two participants were considered to be likely causative for the phenotype, given the strong clinical correlation (likely-causative variant of uncertain significance, LcVUS). On considering these two participants and an additional 28 participants with significant variants in autism candidate genes (vACG), the net diagnostic yield increased to 37.9%. The clinical benefits among those receiving a definite genetic diagnosis (P/LP variants only) included better prognostication (100%), availing reproductive counselling (100%), disease-specific surveillance (86.4%), and therapeutic implications (27.3%). Thus, in conclusion, in our cohort of 137 children with ASD, tES provided a definite genetic diagnosis in 16.1% of the participants, the yield being higher in syndromic ASD. A confirmed genetic diagnosis aided in holistic clinical care, extending beyond reproductive counselling.

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3. Bast N, Ahmad J, Mason L, Jones EJH, Matyjek M, Polzer L, Luckhardt C, Müller AK, McAlonan GM, Banaschewski T, Baumeister S, Loth E, Freitag CM. Locus coeruleus tonic upregulation increases selectivity to inconspicuous auditory information in autistic compared to non-autistic individuals: a combined pupillometry and electroencephalography study. Mol Autism. 2025; 16(1): 41.

BACKGROUND: Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing. METHODS: Autistic (n = 139) and non-autistic (n = 98) individuals were assessed during a passive auditory oddball task with pupillometry and electroencephalography. For every trial, a baseline pupil size (BPS) assessed LC-NE tonic activity that coincides with current arousal, while a stimulus-evoked pupillary response (SEPR) assessed LC-NE phasic activity that estimated sensory selectivity. Electroencephalography assessed amplitudes of mismatch negativity (MMN-amp) that estimated pre-attentive change detection as a brain-activity readout of sensory selectivity. Measures were modeled between groups within the task by combining Frequentist and Bayesian approaches. RESULTS: Across groups, higher BPS was associated with more negative MMN-amp to standards and oddballs. A more negative MMN-amp to standards was associated with a higher SEPR to standards. Controlling for these associations, autistic versus non-autistic individuals showed a higher SEPR in response to standards. In addition, a positive association of BPS and SEPR to standards was specific to autistic individuals. With task progression, autistic versus non-autistic individuals showed a higher initial increase and subsequently steeper decrease of BPS. This was supported by Bayesian posterior distribution estimates. LIMITATIONS: A short trial duration required concatenating trials to epochs and applying a linear-time invariant filter to capture the slow pupil changes. Without an LC-NE manipulation, we cannot rule out that pupil changes are evoked by other cortical pathways than the LC-NE. CONCLUSIONS: Across groups, LC-NE tonic upregulation is emphasized as a general mechanism that un-specifically increases pre-attentive change detection to all sensory stimuli, which then increases sensory selectivity to frequent stimuli. In autistic individuals, different sensory processing is characterized by increased sensory selectivity to frequent stimuli. This is likely caused by an LC-NE tonic upregulation. It associates autistic sensory processing with increased arousal upregulation that increases sensory selectivity to inconspicuous auditory information.

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4. Bravo-Muñoz F, Bustos I, Muñoz-Fierro D, San-Martín S, Tabilo C, Véliz M, Zaror T, Ormazabal P, Brusselaers N, Fornes R. « Risk of Autism Spectrum Disorder in Descendants of Women With Gestational Diabetes and Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis ». Autism Res. 2025.

Some reports show that children exposed to hyperandrogenemia or hyperglycemic states in utero are more prone to be diagnosed with autism spectrum disorder (ASD). This systematic review and meta-analysis aim to assess the association between Polycystic Ovary Syndrome (PCOS) or gestational diabetes (GD) and ASD. A systematic review (1980-2023) in Web of Science, PubMed and Scopus, using specific search terms « gestational diabetes », « polycystic ovary syndrome, » « neurodevelopmental disorder » and « autism spectrum disorder » was performed. Generic inverse-variance method was used to pool the adjusted or crude effect measures with a random-effects model. Results were presented as relative risk (RR) with 95% confidence interval (CI). Only studies from the northern hemisphere were found. All the articles evaluated the association between either GD (n = 16) or PCOS (8) and ASD separately. The overall analysis revealed that there is an increased risk of ASD in the offspring of women diagnosed with GD [RR = 1.23 (95% CI 1.13-1.34), n = 14] and in women diagnosed with PCOS [RR = 1.35 (95% CI 1.17-1.56), n = 6]. In a sensitivity analysis, the risk of ASD was particularly higher in mothers with GD and obesity. Although both GD and PCOS have been associated with ASD in offspring, studies in other geographical regions are needed. Future research should investigate how varying androgen levels in PCOS and the timing of GD diagnosis might influence the observed associations. Additional studies are needed to confirm these associations, address potential confounding variables, and explore whether these maternal conditions contribute directly or indirectly to autism risk.

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5. Cimmino F, Petrella L, Cristiano C, Cavaliere G, Penna E, Pizzella A, Pirozzi C, Fogliano C, Coretti L, Lembo F, Canani RB, Avallone B, Crispino M, Trinchese G, Mollica MP. Autism spectrum disorders and nutritional interventions: dimethylglycine and B-vitamins effects on behaviour, inflammation, microbiota and mitochondria in liver and brain synapses. Biomed Pharmacother. 2025; 191: 118477.

Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions with a multifactorial etiology, where genetic and environmental interactions lead to cellular dysfunctions in the brain and peripheral tissues, associated with dysbiosis, inflammation, oxidative stress, and mitochondrial impairment. Emerging evidence highlights the critical role of the gut microbiota in the metabolic and neuroinflammatory imbalances observed in ASD. In this context, the liver plays a pivotal metabolic role, being closely connected to the gut and brain through metabolic pathways, influencing overall health. Since nutritional interventions and bioactive food compounds are key modulators of these processes, this study aims to investigate the effects of dietary supplementation with dimethylglycine and B group vitamins on the metabolic and inflammatory state of BTBR mice, a well-established model of ASD, focusing on the gut-liver-brain axis. Our findings indicate that dimethylglycine and B group vitamins administration in BTBR mice mitigates ASD-like behaviors. This beneficial effect may be the result of multiple mechanisms as decrease in oxidative stress and inflammatory state, modulation of gut microbiota and body composition, reduced hepatic steatosis, and improved mitochondria functions in liver, brain cortex and synaptic areas. These results suggest that dietary supplementation with dimethylglycine and B vitamins can positively modulate the gut-liver-brain axis in ASD, offering new insights into metabolic and neuroinflammatory interventions.

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6. Colville G. Siblings’ reflections on what it is like to have an autistic brother or sister with additional needs. Evid Based Nurs. 2025.

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7. Gruner M, Roessner V, Ring M. Assessing Anxiety in Autistic and Non-Autistic Youth: Validation of the German Parent Version of the Anxiety Scale for Children With Autism Spectrum Disorder. Autism Res. 2025.

Anxiety is a prevalent co-occurring disorder in autistic youth, yet its accurate assessment remains challenging due to symptom overlap with autism. The Anxiety Scale for Children with Autism Spectrum Disorder-Parent Version (ASC-ASD-P) was designed to address this issue, but its utility in German clinical settings has not been established. This study validated the German translation of the ASC-ASD-P in a clinical sample of 317 participants presenting at a clinic for autism assessment, including 120 autistic youth. Internal consistency was excellent (Cronbach’s α = 0.92), and convergent validity was demonstrated through significant correlations with established psychopathology measures such as the Child Behavior Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Factor analyses preferred a 4-factor structure in the autism group, but indicated difficulties replicating the Separation Anxiety Subscale. Autistic youth showed higher total anxiety and uncertainty scores compared to non-autistic youth, underlining the scale’s sensitivity to autism-specific anxiety patterns. By including youth with intellectual disabilities, often underrepresented in research, this study provides a more comprehensive evaluation of the ASC-ASD-P’s applicability across the autism spectrum. These findings support the ASC-ASD-P as a reliable tool for assessing anxiety in German-speaking autistic youth while highlighting areas where refinement could strengthen its utility.

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8. Hsu CL, Matt E, Fong TKH, Lam JYT, Chau B, Cheng CPW, Beisteiner R, Cheung T. Associations Between Brain Network Connectivity and Cognitive Measures in Autism Spectrum Disorder: A Post Hoc Analysis of a Parent Study « Evaluating the Safety and Efficacy of Transcranial Pulse Stimulation on Autism Spectrum Disorder ». Autism Res. 2025.

This study presents a post hoc analysis of our parent study « Evaluating the Safety and Efficacy of Transcranial Pulse Stimulation on Autism Spectrum Disorder » study which was a double-blind, sham-controlled, randomized controlled trial. In this study, we examined associations between changes in brain network connectivity and cognitive performance in young adolescents (12-17 years) with autism spectrum disorder (ASD) following the administration of transcranial pulse stimulation (TPS) which is considered non-invasive, evidenced-based brain stimulation for neurodegenerative disorders and neuropsychiatric disorders. Our findings indicate that increased connectivity in specific brain networks is associated with improvements in cognitive measures, suggesting that connectivity changes may underpin cognitive changes observed after six TPS intervention. These results highlight potential neural mechanisms underlying cognitive improvements in ASD, although causality cannot be inferred from these associations. Trial Registration: ClinicalTrials.gov identifier: NCT05408793.

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9. Kaş Alay G, Kaçan H, Kurtoğlu S. Experiences, Difficulties, and Coping Mechanisms of Parents With Children With Autism: A Phenomenology Study in Türkiye. J Child Adolesc Psychiatr Nurs. 2025; 38(3): e70035.

BACKGROUND: Autism spectrum disorder (ASD) has the potential to create a number of challenges and problems for parents due to having lifelong problem behaviors. PURPOSE: The aim of this qualitative study was to explore the experiences, difficulties, and coping mechanisms of parents with children with ASD through a multidisciplinary team approach. METHODOLOGY: This study employed a descriptive qualitative research methodology. Data were collected through semi-structured, face-to-face individual interviews with 12 parents, guided by a structured interview protocol. Data management and analysis were conducted using the MAXQDA program. A thematic approach was used in data analysis. RESULTS: Participants reported experiencing both challenges and positive emotions related to raising a child diagnosed with ASD, and described a variety of coping strategies. Thematic analysis of the interview data revealed five key themes centered on parental perspectives: (1) parenting a child with ASD, (2) families’ reactions to the diagnosis, (3) psychological and social difficulties, (4) future-related concerns, and (5) perceived support needs. CONCLUSIONS: Parents of children have ASD have to cope with many problems throughout their lives. Resources are needed to support parents bio-psycho-socially. Enhancing the provision of standardized education and support to parents can be achieved by improving existing health and social policies, establishing formal support networks, and facilitating access to childcare services.

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10. Kim SW, Lee H, Song DY, Lee GH, Han JH, Lee JW, Byun HJ, Son JH, Kim YR, Lee Y, Kim E, Werling DM, Kim SH, Sanders SJ, Yoo HJ, An JY. Evaluation of familial phenotype deviation to measure the impact of de novo mutations in autism. Genome Med. 2025; 17(1): 93.

BACKGROUND: The phenotypic outcomes of de novo variants (DNVs) in autism spectrum disorder (ASD) exhibit wide variability. To date, no study has comprehensively estimated DNV effects accounting for familial phenotypic background. METHODS: To evaluate DNV effects in a family-relative context, we defined within-family standardized deviations (WFSD) by subtracting phenotype scores of unaffected family members and standardizing the result. We applied this approach to 78,685 individuals from 21,735 families from ASD cohorts of diverse ancestries. We compared the distribution, associations with disruptive DNVs, and gene discovery results between WFSD and raw phenotype scores. We further performed outlier analysis based on WFSDs per gene to detect genes with high variability between families. RESULTS: We observed that ASD probands with disruptive DNVs exhibited greater behavioral symptoms and lower adaptive functioning relative to their within-family unaffected members. Compared to raw phenotype scores, WFSD provided clearer associations with DNVs and enabled greater yield in DNV-enriched gene discovery, including 18 novel ASD-associated genes. Outlier analysis identified 11 genes with high intrafamilial variability in phenotypic effects, influenced by mutation sites within functional domains or exons. CONCLUSIONS: Familial DNV analysis provides accurate effect estimates, a reliable basis for predicting clinical outcomes, and precise support while minimizing confounding from family background. This approach improves the identification of ASD-associated genes with true phenotypic effects by reducing variability, as well as genes with genuine phenotypic heterogeneity across families driven by mutation site. These findings enhance our understanding of ASD phenotype variability and inform potential targets for intervention.

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11. Mourad J, Grosjean B, Perroud N, Bogaerts K, Desseilles M, Bonnechère B. Rethinking body representations in autism across cultures. Front Psychiatry. 2025; 16: 1612219.

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12. Murray DS, Anixt JS, Vasudevan V, Cole LL, Fedele A, Karpur A, Cornell WL, Latten LM, Butter EM, Coury DL. Preferences for Outcome Data Collection and Access in a Pediatric Autism Learning Health Network Registry. J Dev Behav Pediatr. 2025.

OBJECTIVE: Health professionals participating in learning health networks collect data for informing clinical decision-making, research, and quality improvement (QI). To optimize the collection and use of clinical and Parent Reported Outcome (PRO) data for these purposes, it is important to understand the priorities of patient registry « end users » (clinicians, researchers, and patients/families). METHODS: The analysis used a sequential mixed-methods approach with parent (n = 93) and clinician (n = 167) surveys followed by targeted interviews (parent n = 9, clinician/researcher n = 7) completed at Autism Care Network (ACNet) sites to better understand current use of registry data and parent/clinician priorities. RESULTS: Sixty percent of parents reported receiving behavioral data regarding their child from their health provider in the past, and 90% felt these data would help them understand their child’s behavior. Among data access options parents preferred an online portal (72%) and/or the clinic’s electronic medical record (59%). Parents indicated willingness to complete surveys longitudinally if the assessments correlated with their child’s specific areas of difficulty. Priorities for clinicians included easy access to the data (84%), meaningful connection to clinical outcomes (81%), and measures that can demonstrate change in symptoms over time (76%) and that are easy for families to complete (80%). Both groups recommend assessing parenting stress and social determinants of health. CONCLUSION: Consideration of end-user priorities can improve patient registry data collection, analysis, and utilization. Families may be more willing to participate if they can receive direct benefit by accessing their own data and clinicians use this data to optimize clinical care.

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13. Nieto C, Gandía-Abellán H, Sorrel MA, Garrido-Salcedo M. Development and validation of the AIDA scale: Anxiety in people with autism and intellectual disability assessment. J Intellect Dev Disabil. 2025: 1-13.

BACKGROUND: Minimally verbal autistic people with intellectual disabilities are at risk of anxiety, yet remain underrepresented in research due to the lack of tools adapted to their functional profiles. This study aimed to develop and validate the AIDA Scale: Anxiety in People with Autism and Intellectual Disability Assessment. METHOD: A total of 247 participants (133 parents; 114 professionals) contributed across three phases: indicator identification, pilot study, and validation. RESULTS: Evidence of reliability (internal consistency and omega coefficient) and validity was gathered, including examination of the scale’s dimensionality (parallel analysis, model fit indices, and factor loadings inspection) and its relationship with other variables. Findings support the use of a single total score encompassing general behaviour and behavioural change indicators. CONCLUSION: The AIDA Scale is an effective tool for assessing anxiety symptoms in this population. Meeting these needs is critical for improving emotional wellbeing and ensuring people’ rights to appropriate emotional care.

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14. Park H, Choi JH, Choi SJ. Enhanced Postural Control Through Textured Insoles in Adults With Autism Spectrum Disorder: A Sensorimotor Integration Perspective. Motor Control. 2025: 1-25.

This study investigated the effects of textured insoles on postural control in adults with autism spectrum disorder (ASD), examining how enhanced somatosensory feedback influences sensorimotor integration under varying sensory conditions. Twenty-one adults with ASD (Mage = 28.4 ± 4.2 years) participated in a within-subjects design study with a 2 × 2 × 2 factorial design (surface: firm/foam, vision: eyes open/closed, and insole: with/without). Postural control was assessed using the Gaitview AFA-50 pressure platform system. Center of pressure parameters, including envelope area, root mean square, and total path length were analyzed to evaluate spatial and temporal aspects of postural control performance. The results showed that textured insoles significantly reduced postural sway parameters, indicating improved postural control, most significantly in conditions where sensorimotor integration was challenging (eyes closed on foam surface). Envelope area was reduced by 45.2% (p < .01), root mean square by 38.2% (p < .001), and total path length by 31.1% (p < .001), indicating improved postural control. Astrong interaction between surface type and insole condition was found particularly for root mean square (ηp2 = .685, p < .001), suggesting that the effects of somatosensory enhancement are greater when proprioceptive information is limited. Our results suggest that textured insoles reduce postural sway in adults with ASD, indicating improved postural control by enhancing plantar somatosensory feedback. This sensory augmentation may compensate for sensory integration difficulties commonly observed in ASD by strengthening one sensory channel, potentially facilitating more effective multisensory integration for postural control.

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15. Rai S. A novel hybrid deep learning model using MEResNextfor autism spectrum disorder detection. Comput Biol Chem. 2025; 120(Pt 1): 108619.

A neurological disease, named autism spectrum disorder (ASD), is portrayed through divergence with social interaction, communication, and repetitive activities. As heredity is an important source, initial identification and treatment can diminish the need for wide examinations and expensive medical procedures for those with ASD. Prolonged effects and severity can be avoided at a timely determination of ASD. This study develops a hybrid deep-learning method for ASD detection. Pre-processing, feature selection and ASD detection are three steps involved. In thepre-processing phase, input data is passed in which noise and artefacts present in the data are removed using Yeo-Jhonson transformation. Next, by integrating Double exponential Smoothing (DES) in Elk Herd Optimizer (EHO), Double exponential Smoothing-Elk Herd Optimizer (DeSEHO),is proposed to select features. At last, the features that are selected are subjected to the ASD detection phase. In this stage, the Moments Embedding ResNeXt (MEResNeXt), which is the combination of Moments Embedding Network (MoNet) and ResNeXt, is used for ASD detection. The results of the research show that MEResNeXtperformed better in terms of traditionalmodelswhich show accuracyof95.3 %, sensitivity of 96.5 %, and specificity of 94.8 %.

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16. Rosenbaum P. Viewpoint: childhood developmental disability: recognising the primary role of the family. BMJ Paediatr Open. 2025; 9(1).

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17. Shah J, Mondal D, Jain D, Mhatre P, Patel K, Iyer A, Pandya M, Menghani B, Dave G, Sheth J, Sheth F, Ramdas S, Sheth H. Long read whole genome sequencing-based discovery of structural variants and their role in aetiology of non-syndromic autism spectrum disorder in India. BMC Med Genomics. 2025; 18(1): 131.

BACKGROUND: Despite having heritability estimates of 80%, ~ 50% cases of autism spectrum disorders (ASD) remain without a genetic diagnosis. Structural variants (SVs) detected using long-read whole genome sequencing (lrWGS) are a relatively new class of variants implicated in neurodevelopmental disorders. Short read sequencing (SRS) and chromosomal microarray (CMA) are unable to resolve these SVs due to their inherent technological limitations. This study was aimed to detect and delineate the role of SVs in children with non-syndromic ASDs using lrWGS in whom prior traditional genetic tests did not yield a definitive genetic diagnosis. METHODS: A total of 23 patients with no prior genetic diagnosis from karyotyping, Fragile-X analysis, CMA and short read whole exome sequencing (srWES) were selected for lrWGS using Oxford Nanopore based sequencing platform. Samples were sequenced at an average coverage of ~ 7x. Contigs generated from high accuracy base calling were aligned against GRCh38/hg38 human reference genome build. SVs were called using five variant callers- Sniffles2, cuteSV, NanoVar, SVIM, and npInv, and annotated using AnnotSV. Calls from cuteSV were used as benchmark to identify concordant calls across at least three variant callers. RESULTS: An average whole genome coverage of ~ 7x and N50 read length of 6.65 ± 3.3 kb was obtained across 46 runs (two runs/ sample). On average, a total of approximately 235,163 calls were made across all callers for each sample. The average number of deletions, duplications, insertions, inversions and translocations were 54,787, 3,335, 62,459, 1,286, and 113,296, respectively, were detected across all callers per sample. Of 23 cases, a candidate SV, an inversion of approximately 2.7 Mb in size encompassing SNAP25-AS1 gene was observed. This gene is likely to be involved in the synaptic pathway and has previously been associated with autism. CONCLUSION: This is the first study from India to assess the role of SVs in the aetiology of non-syndromic ASDs. Despite the small sample size, low-pass genome coverage, and modest N50 read length, the study indicates a modest contribution of SVs in the aetiology of non-syndromic ASD. Dearth of data supporting the role of SVs in non-syndromic ASDs in other cohorts from around the world further supports our conclusion.

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18. Vallese A, Melija S, Hayek J, Pecorelli A, Valacchi G. Deregulated Nrf2-Keap1-BACH1 axis in autism spectrum disorder. Redox Biol. 2025; 86: 103837.

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments in social communication, restricted interests, and repetitive behaviors. Although its etiology remains incompletely understood, increasing evidence suggests a multifactorial origin involving genetic alterations, immune dysregulation, and environmental exposures. The aim of this study was to investigate the redox-sensitive Nrf2 signaling pathway in primary dermal fibroblasts isolated from ASD patients. Our results revealed constitutive activation of Nrf2, accompanied by reduced expression of its downstream target heme oxygenase-1 (HO1) and marked nuclear accumulation of the transcriptional repressor BACH1 in ASD cells. Moreover, ASD fibroblasts failed to increase Nrf2 nuclear translocation upon sulforaphane (SFN) stimulation, a response consistent with elevated basal levels of Keap1, a negative regulator that sequesters Nrf2 in the cytoplasm. Notably, treatment with hemin, known to induce nuclear export and degradation of BACH1, successfully restored HO1 gene and protein expression and ameliorated impaired mitochondrial function in ASD fibroblasts, as suggested by the decrease of mtROS levels and the restored mitochondrial membrane potential. Collectively, these results identify a dysregulation of the Nrf2-Keap1-BACH1 axis in ASD and suggest that pharmacological targeting of this pathway may offer therapeutic potential to correct the redox imbalance associated with the disorder.

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19. Zhong L, Ren P, Wang H, Fu C, Feng D, Wang M, Zeng L, Yao P, Wang T. Potential association between altered oral microbiota and oxidative stress in individuals with autism. Autism. 2025: 13623613251362259.

Autism spectrum disorders are potentially associated with gastrointestinal dysfunction, although the underlying mechanisms remain unclear. Recently, the oral cavity has gained attention as the starting point of the digestive tract. We aim to explore the potential association between altered oral microbiota and oxidative stress in individuals with autism spectrum disorders. We conducted a case-control study involving 54 subjects with autism spectrum disorders and 46 typically developing participants. Oral epithelial cells and saliva samples were collected to analyze oxidative stress markers and oral microbiota composition using 16S rDNA sequencing. Compared with typically developing participants, individuals with autism spectrum disorders exhibited suppressed mRNA levels of superoxide dismutase 2 and RAR-related orphan receptor α, increased H3K9me2 modifications at superoxide dismutase 2 promoter, elevated levels of 8-oxo-dG in oral epithelial cells, and a reduced ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in saliva. In addition, alpha and beta diversity analyses showed significant differences in microbial richness, evenness, and intersample variation between the autism spectrum disorder and typically developing groups. Statistical analyses confirmed marked distinctions in microbial diversity and community structure between the two groups. Individuals with autism spectrum disorders show increased oxidative stress and altered oral microbiota compared with typically developing participants. While the underlying mechanisms remain unclear, these findings suggest that altered oral microbiota may be linked to oxidative stress, providing insights into autism spectrum disorder pathology and potential avenues for clinical intervention.Lay AbstractAutism spectrum disorders are linked to gut-related issues, but the exact causes are still unclear. Recent research focuses on the mouth, the first part of the digestive system, to understand how it may play a role. This study looked at how the oral microbiome (the community of microorganisms in the mouth) and oxidative stress (an imbalance between harmful free radicals and antioxidants in the body) differ in people with autism spectrum disorders compared with typically developing individuals. Researchers studied 54 people with autism spectrum disorders and 46 typically developing individuals by analyzing their saliva and oral cells. Results showed that people with autism spectrum disorders had higher levels of oxidative stress markers and noticeable differences in their oral microbiota diversity and structure. These findings suggest a potential connection between changes in oral bacteria and oxidative stress in autism spectrum disorders, opening the door for new ways to study and treat autism spectrum disorders-related health issues.

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