1. Al-Srehan H, Ayasrah MN, Al-Rousan AH, Khasawneh MAS, Gharaibeh M. Predicting Suicidal Ideation Among Youths With Autism Spectrum Disorder: An Advanced Machine Learning Study. Clin Psychol Psychother. 2025; 32(3): e70082.

This study aimed to predict suicidal ideation among youth with autism spectrum disorder (ASD) by applying machine learning techniques. A cross-sectional sample of 368 ASD-diagnosed young people (aged 18-24 years) was recruited, and 34 candidate predictors-including sociodemographic characteristics, psychiatric symptoms (e.g., anxiety problems and depressive symptoms), behavioural measures (e.g., bullying victimization and insomnia severity) and adverse childhood experiences-were assessed using standardized instruments and parent-report checklists. After listwise deletion of missing data, recursive feature elimination (RFE) with a random forest wrapper was performed to identify the five most influential predictors. Four classification algorithms (logistic regression, random forest, eXtreme Gradient Boosting [XGBoost] and support vector machine [SVM]) were then trained on a 70/30 stratified split and evaluated on the hold-out test set using area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value and accuracy. RFE identified anxiety problems, insomnia, bullying victimization, age and depression (PHQ-9) as the top predictors. Logistic regression achieved an AUC of 0.943 (sensitivity = 0.773, specificity = 0.957 and accuracy = 0.922), random forest an AUC of 0.948 (sensitivity = 0.727, specificity = 0.989 and accuracy = 0.939), XGBoost an AUC of 0.930 (sensitivity = 0.772, specificity = 0.989 and accuracy = 0.947) and SVM an AUC of 0.942 (sensitivity = 0.772, specificity = 0.978 and accuracy = 0.939). Across models, anxiety and insomnia emerged as the two most important risk factors, and XGBoost demonstrated the best overall balance of performance metrics, yielding the highest accuracy. Gradient-boosted tree models were thus shown to effectively integrate multidimensional data to predict suicidality in autistic youth, highlighting anxiety and sleep disturbances as critical targets for personalized risk assessment and prevention efforts.

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2. Ashwlayan VD, Ratnesh RK, Sharma D, Sharma A, Sangal A, Saifi A, Singh J. A Comprehensive Review on Plant-Based Medications and Chemical Approaches for Autism Spectrum Disorders (ASDs) Psychopharmacotherapy. Indian J Microbiol. 2025; 65(1): 15-31.

Gastrointestinal impairment induced sleep, behavioral and psychiatric disorders were reported in patients of autism spectrum disorders (ASDs). These may be life-long neuro-developmental disorders. Standardized diagnostic criteria for ASDs include: restricted and repetitive behavior, ongoing deficiencies in social interaction and communication. Pro-antioxidant and anti-inflammatory effects of dietry polyphenols/poly-phenol-rich derivatives as bioactive compounds enhanced permeability of blood brain barrier, consequently leads to delay in the onset of ASDs symptoms and can be effectively used in the management of ASDs. During the research on ASDs numerous therapeutic modalities, such as chemical and plant-based therapies, have been investigated. Due to their possible neuro-psychopharmacological benefits, plant-based treatments have attracted interest. These natural source therapies have demonstrated potential in reducing ASDs-related symptoms. Plant-based psycho-pharmaceuticals have been thoroughly investigated, and the investigations have confirmed their therapeutic effects. The therapeutic qualities of plants not only address the complex neurological aspects of ASDs but also provide a comprehensive approach to treatment. These substances may restore neurochemical equilibrium by focusing on particular biochemical pathways associated with the illness. Advancements in pharmacology and neurochemistry have enabled targeted interventions through chemical approaches. The treatment of ASDs approached through a combination of plant-based solutions and chemical methods can be better than one alone. By targeting the restorative properties of both natural compounds and synthesized chemicals, researchers aim to address the diverse range of symptoms and underlying neurobiological abnormalities associated with ASDs. Further clinical studies are required to validate the potential of bioactive molecules scientifically.

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3. Bernie C, Montgomery A, Sealy L, Descallar J, Dissanayake C, Jalaludin B, Murphy E, Woolfenden S, Williams K, Eapen V. Sensitivity and Specificity of Developmental Surveillance and Autism Screening in an Australian Multicultural Cohort: The Watch Me Grow Study. J Autism Dev Disord. 2025.

To examine accuracy of two-tiered surveillance to detect developmental disability and autism in a multicultural birth cohort; a subset of the Watch Me Grow Study. Surveillance tools were used at or soon after 18 months of age, including the Parents’ Evaluation of Developmental Status (PEDS), the Ages and Stages Questionnaire (ASQ-3), and the revised Modified Checklist for Autism in Toddlers (M-CHAT-R/F). Children with and without identified concerns were assessed between 18 and 23 months using the Mullen Scales of Early Learning (MSEL) and the Autism Diagnostic Observation Schedule-2 (ADOS-2). Sensitivity and specificity of the surveillance tools used in isolation and in combination in this cohort ranged from 51 to 87% (n = 165). Some children (n = 21) who were not identified with high likelihood of difficulties were later assessed as having probable developmental disability. Adding the M-CHAT-R/F did not significantly improve autism likelihood identification in comparison with tiered developmental surveillance. There was highly variable sensitivity and specificity of combined tools for tiered developmental surveillance in this cohort. There remains a need in Australia to improve methods of, and engagement in, developmental screening and surveillance that includes detection of concerns in community and primary healthcare settings.

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4. Chang Z, Yao H, Sun S, Zhang L, Liu S, Brikell I, D’Onofrio BM, Larsson H, Lichtenstein P, Kuja-Halkola R, Hägg S, Happé F, Taylor MJ. Association between autism and dementia across generations: evidence from a family study of the Swedish population. Mol Psychiatry. 2025.

There is emerging evidence to suggest that autistic individuals are at an increased risk for cognitive decline or dementia. It is unknown whether this association is due to shared familial influences between autism and dementia. The main purpose of this study was, thus, to investigate the risk of dementia in relatives of autistic individuals. We conducted a family study based on linking Swedish registers. We identified all individuals born in Sweden from 1980-2013, followed until 2020, and clinical diagnoses of autism among these individuals. We linked these index individuals with their parents, grandparents, and aunts/uncles. The risk of dementia (including any type of dementia, Alzheimer’s disease, and other types of dementia) in relatives of autistic individuals was estimated using Cox proportional hazards models. Analyses were then stratified by sex of the relatives and intellectual disability in autistic individuals. Relatives of autistic individuals were at an increased risk of dementia. The risk was strongest in parents (hazards ratio [HR] = 1.36, 95% confidence intervals = 1.25-1.49), and weaker in grandparents (HR = 1.08, 1.06-1.10) and aunts/uncles (HR = 1.15, 0.96-1.38). Furthermore, there were indications of a stronger association between autism in index individuals and dementia in mothers (HR = 1.51, 1.29-1.77) compared to dementia in fathers (HR = 1.30, 1.16-1.45). There was only a small difference in relatives of autistic individuals with and without intellectual disability. Our results provide evidence of familial co-aggregation between autism and different types of dementia, and a potential genetic link. Future research now needs to clarify the risk of dementia in autistic individuals.

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5. Charki A, Meklaoui FZ, Charki A, Ettouzani A. Examining the association between variation of ASD and cognitive and affective domains of mentalizing in verbal children with ASD. Appl Neuropsychol Child. 2025: 1-11.

Cognitive research in autism has often approached mentalizing abilities in global terms, and ultimately judged them to be impaired in Autism Spectrum Disorder (ASD). However, recent studies have demonstrated that these social-cognitive abilities constitute neurocognitive constructs, encompassing both cognitive and affective domains, which are selectively found to be lacking in clinical categories. This study investigates the variation in autistic symptoms in relation to the graduation in gravity of cognitive and affective domains of mentalizing in children with ASD, aged 8 to 12 years. Mentalizing domains are assessed by the false-belief paradigms and by the Reading the Mind in the Eyes tasks in a group of 50 children with ASD. The findings showed that the severity of the children’s autistic symptoms is inversely and strongly associated with their performance in first-(r = -0.762, p < .001) and second-order cognitive mentalizing (r = -0.674, p < .001), as well as affective mentalizing (r = -0.653, p < .001). However, the capacity for affective mentalizing was noticeably more impaired compared to those of cognitive mentalizing. The evidence confirms that the lower performance of children with ASD in mentalizing abilities is relatively dependent on the variation in their autistic symptoms and that the cognitive and affective domains of the latter are interrelated constructs.

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6. Chen IC, Hsu HC, Chen CL, Chang MH, Wei CS, Chuang CH. Interbrain synchrony attenuation during a peer cooperative task in young children with autistic traits -an EEG hyperscanning study. Neuroimage. 2025; 312: 121217.

Young children with autism spectrum disorder (ASD) traits frequently encounter difficulties in peer interaction. Assessing peer interaction performance is crucial but challenging within the clinical diagnostic paradigm of ASD. Hyperscanning, which simultaneously monitors brain activity in multiple individuals, has become a popular tool for assessing social interaction’s neural features. The present study aims to investigate the brain-to-brain connectivity between child-dyads engaged in a game-like collaborative peer interaction task via the hyperscanning electroencephalogram (EEG) approach. The final sample comprised 66 young children: 18 child dyads with typical development (TD), TD-TD, and 15 with ASD traits matched to TD, TD-ASD. The study indicated a depressed level of connectivity in the dyad group with ASD as the responder, with a notable decrease observed in the beta oscillation over the right parietal to left temporal coupling between subjects. A pattern that differed from that observed in the TD-TD group was identified with regard to full-band connectivity over the right-to-right temporal region. It was observed that the TD-TD group exhibited enhanced connectivity following the completion of the task, which was not the case for the TD-ASD group. Significant correlations were observed between scores on the ASD symptom rating scale and the selected significant interbrain connectivity index. The application of a hyperscanning EEG paradigm demonstrated that the participating children with autistic traits exhibited an attenuated and apparently distinct alteration pattern of interbrain connectivity in comparison to a control group. These findings highlight the value of physiologically based measures in informing etiological and interventional studies in neuropsychiatry.

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7. Crompton CJ, Foster SJ, Wilks CEH, Dodd M, Efthimiou TN, Ropar D, Sasson NJ, Lages M, Fletcher-Watson S. Information transfer within and between autistic and non-autistic people. Nat Hum Behav. 2025.

Autism is clinically defined by social communication deficits, suggesting that autistic people may be less effective at sharing information, particularly with one another. However, recent research indicates that neurotype mismatches, rather than autism itself, degrade information sharing. Here, using the diffusion chain method, we examined information transfer in autistic, non-autistic and mixed-neurotype chains (N = 311), replicating and extending a key study. We hypothesized that information transfer would deteriorate faster and rapport would be lower in mixed-neurotype compared with single-neurotype chains. Additionally, we examined whether informing participants of the diagnostic status of their chain and whether information was fictional or factual impacted performance and rapport. We found no difference in information transfer between single-neurotype and mixed-neurotype chains. Non-autistic chains indicated higher rapport, and disclosing diagnosis improved rapport. This result challenges assumptions about autistic communication deficits but contrasts with prior findings. Enhanced participant heterogeneity and methodological differences may explain these unexpected results. Protocol registration The Stage 1 protocol for this Registered Report was accepted in principle on 23 August 2022. The protocol, as accepted by the journal, can be found at https://osf.io/us9c7/ .

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8. Dias C, Sousa T, Cruz A, Costa D, Mouga S, Castelhano J, Pires G, Castelo-Branco M. A role for preparatory midfrontal theta in autism as revealed by a high executive load brain-computer interface reverse spelling task. Sci Rep. 2025; 15(1): 16671.

Midfrontal theta oscillations have been linked to executive function, yet their role in autism-where this function is often compromised-remains unclear. We hypothesized that preparatory increases in theta power may help normalize performance in autism. To test this, we used a challenging interactive executive function task designed to impose a high working memory load and require constant error monitoring. An electroencephalogram (EEG)-based brain-computer interface (BCI) was used to maximize cognitive load and engagement. Neural activity from autistic and non-autistic adults was compared while participants were asked to mentally reverse pseudowords (engaging working memory) and write them using the BCI, which provided real-time performance feedback (maximizing error monitoring). The study focused on theta power modulation during the preparatory (pre-response) and feedback (post-response) periods but also explored the role of posterior alpha oscillations. Results showed similar task performance between groups, but distinct recruitment of brain resources, particularly during the preparatory period. The finding of an increased preparatory theta in autism favors the hypothesis of compensatory recruitment of cognitive control and attentional mechanisms to achieve accurate results.

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9. Gonzales S, Zhao JZ, Choi NY, Acharya P, Jeong S, Wang X, Lee MY. SOX7: Autism associated gene identified by analysis of multi-Omics data. PLoS One. 2025; 20(5): e0320096.

Genome-wide association studies and next generation sequencing data analyses based on DNA information have identified thousands of mutations associated with autism spectrum disorder (ASD). However, more than 99% of identified mutations are non-coding. Thus, it is unclear which of these mutations might be functional and thus potentially causal variants. Transcriptomic profiling using total RNA-sequencing has been one of the most utilized approaches to link protein levels to genetic information at the molecular level. The transcriptome captures molecular genomic complexity that the DNA sequence solely does not. Some mutations alter a gene’s DNA sequence but do not necessarily change expression and/or protein function. To date, few common variants reliably associated with the diagnosis status of ASD despite consistently high estimates of heritability. In addition, reliable biomarkers used to diagnose ASD or molecular mechanisms to define the severity of ASD do not exist. Therefore, it is necessary to integrate DNA and RNA testing together to identify true causal genes and propose useful biomarkers for ASD. We performed gene-based association studies with adaptive test using genome-wide association studies’ (GWAS) summary statistics with two large GWAS datasets (ASD 2019 data: 18,382 ASD cases and 27,969 controls [discovery data]; ASD 2017 data: 6,197 ASD cases and 7,377 controls [replication data]) which were obtained from the Psychiatric Genomics Consortium (PGC). In addition, we investigated differential expression between ASD cases and controls for genes identified in gene-based GWAS with two RNA-seq datasets (GSE211154: 20 cases and 19 controls; GSE30573: 3 cases and 3 controls). We identified 5 genes significantly associated with ASD in ASD 2019 data (KIZ-AS1, p = 8.67 × 10-10; KIZ, p = 1.16 × 10-9; XRN2, p = 7.73 × 10-9; SOX7, p = 2.22 × 10-7; LOC101929229 also known as PINX1-DT, p = 2.14 × 10-6). Among these 5 genes, gene SOX7 (p = 0.00087) and LOC101929229 (p = 0.009) were replicated in ASD 2017 data. KIZ-AS1 (p = 0.059) and KIZ (p = 0.06) were close to the boundary of replication in ASD 2017 data. Genes SOX7 (p = 0.036 in all samples; p = 0.044 in white samples) indicated significant expression differences between cases and controls in the GSE211154 RNA-seq data. Furthermore, gene SOX7 was upregulated in cases than in controls in the GSE30573 RNA-seq data (p = 0.0017; Benjamini-Hochberg adjusted p = 0.0085). SOX7 encodes a member of the SOX (SRY-related HMG-box) family of transcription factors pivotally contributing to determining of the cell fate and identity in many lineages. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins leading to autism. Gene SOX7 in the transcription factor family could be associated with ASD. This finding may provide new diagnostic and therapeutic strategies for ASD.

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10. Hinten AE, Schluter PJ, van Deurs J, van Noorden L, McLay L. Outcomes of participating in the Let’s Play programme on 0-5-year-old autistic children’s engagement and caregivers’ stress: study protocol for a parallel randomised controlled trial. BMJ Open. 2025; 15(5): e081030.

INTRODUCTION: Vast empirical evidence highlights the importance of early identification, diagnosis and support for autistic children. Caregivers of autistic children often experience high levels of psychological distress; hence there is a need for parallel child and caregiver support. Autism New Zealand’s Let’s Play programme is a caregiver-mediated, community-based programme based on the principles of developmental and relational interventions (henceforth, developmental). Developmental interventions are evidence-based supports designed to enhance children’s learning within the context of developmentally appropriate, naturalistic settings (eg, everyday routines, play). We aim to evaluate the effects of the Let’s Play programme on autistic children’s engagement and caregiver stress. METHODS AND ANALYSIS: This study will be a single-blind (rater) randomised controlled trial with two parallel arms: immediate programme access (intervention) versus a waitlist control. Participants will be 64 caregivers of children aged 0-5 years with diagnosed or suspected autism, allowing for 20% attrition, based on power calculations. The Let’s Play programme will be delivered over 9 weeks using a combination of small group workshops and in-home coaching. Primary outcome variables include child engagement and caregiver stress. Caregivers will complete measures at three time points (baseline, immediately post-programme and at the 6-month follow-up), and effectiveness will be analysed using generalised estimating equation models and intention-to-treat and per protocol analyses. ETHICS AND DISSEMINATION: This trial was approved by Aotearoa New Zealand Ministry of Health’s Health and Disability Ethics Committee (2022 FULL 13041). Findings will be communicated nationally and internationally via conferences, journal publications and stakeholder groups (eg, service providers for autistic children). Results will be shared regardless of magnitude or direction of effect. TRIAL REGISTRATION NUMBER: ACTRN12622001139763.

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11. Huang WL, Leventhal B, Lin CC, Chien YL. Health anxiety and somatic symptoms in adults on the autism spectrum. Psychiatry Res. 2025; 350: 116550.

BACKGROUND: Somatic symptoms and health anxiety impact quality of life. Whether somatic symptoms and health anxiety correlate with autistic traits, anxiety/depression, sensory and personality characteristics has yet to be systematically investigated among autistic people. This study aimed to investigate somatic symptoms and health anxiety in autistic, and their clinical correlates. METHODS: This study recruited 221 autistic adults (aged 28.1±8.5), 514 somatic symptom disorder (SSD), 194 anxiety or depressive disorders (affective disorder group, AFD), and 555 non-autistic controls. All participants completed the Health Anxiety Questionnaire and Patient Health Questionnaire-15 scales to assess health anxiety and somatic symptoms. RESULTS: Autistic adults showed greater somatic symptoms and health anxiety than non-autistic controls. The level was similar to the AFD but lower than the SSD groups. Harm avoidance and low registration were associated with health anxiety and somatic symptoms in autism, while attention to details was positively associated with the needs of reassurance. Health-related anxiety was related to both depression and anxiety, and most domains on quality of life, with excessive health-related worries associated with greater anxiety and lower environmental life quality. CONCLUSION: Findings suggest significant somatic symptoms and health anxiety in autistic adults that warrants clinical attention.

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12. Jibon MDK, Islam MA, Hosen ME, Faruqe MO, Zaman R, Acharjee UK, Sikdar B, Tiruneh YK, Khalekuzzaman M, Jawi M, Zaki MEA. In-silico analysis of deleterious non-synonymous SNPs in the human AVPR1a gene linked to autism. BMC Genomics. 2025; 26(1): 492.

Single nucleotide polymorphisms are the most prevalent type of DNA variation occurring at a single nucleotide within the genomic sequence. The AVPR1a gene exhibits genetic polymorphism and is linked to neurological and developmental problems, including autism spectrum disorder. Due to the difficulties of studying all non-synonymous single nucleotide polymorphisms (nsSNPs) of the AVPR1a gene in the general population, our goal is to use a computational approach to identify the most detrimental nsSNPs of the AVPR1a gene. We employed several bioinformatics tools, such as SNPnexus, PROVEAN, PANTHER, PhD-SNP, SNP & GO, and I-Mutant2.0, to detect the 23 most detrimental mutants (R85H, D202N, E54G, H92P, D148Y, C203G, V297M, D148V, S182N, Q108L, R149C, G212V, M145T, G212S, Y140S, F207V, Q108H, W219G, R284W, L93F, P156R, F136C, P107L). Later, we used other bioinformatics tools to perform domain and conservation analysis. We analyzed the consequences of high‑risk nsSNPs on active sites, post-translational modification (PTM) sites, and their functional effects on protein stability. 3D modeling, structure validation, protein-ligand binding affinity prediction, and Protein-protein docking were conducted to verify the presence of five significant substitutions (R284W, Y140S, P107L, R149C, and F207V) and explore the modifications induced due to these mutants. These non-synonymous single nucleotide polymorphisms can potentially be the focus of future investigations into various illnesses caused by AVPR1a malfunction. Employing in-silico methodologies to evaluate AVPR1a gene variants will facilitate the coordination of extensive investigations and the formulation of specific therapeutic approaches for diseases associated with these variations.

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13. Kılıç KD, Çakar B, Uyanıkgil Y, Koenhemsi L, Güneş B, Eroğlu E, Erbaş O. Therapeutic effect of bismuth subsalicylate in a propionic acid-induced autism model. Naunyn Schmiedebergs Arch Pharmacol. 2025.

Inflammation-induced oxidative stress in macrophages and microglia is associated with excessive production of reactive oxygen species, initiating a damaging cycle of neuroinflammation and cellular injury. These processes are significant contributors to the pathophysiology of autism spectrum disorders, which involve neuronal dysfunction, cell loss, and behavioral impairments. Under conditions of oxidative stress, activated microglia release pro-inflammatory mediators, further intensifying neuronal damage. Bismuth subsalicylate (BSS), a compound with well-documented anti-inflammatory and antioxidant properties, has shown potential in mitigating such neurodegenerative processes. This study aimed to evaluate the effects of BSS in reducing neuroinflammation and oxidative stress in a propionic acid (PPA)-induced autism model, alongside its impact on behavioral outcomes. The study utilized 30 male Wistar albino rats, with PPA administered intraperitoneally at 250 mg/kg/day for 5 days to induce an autism-like phenotype. Rats were divided into three groups: Group 1 (Normal control, n = 10); Group 2 (PPA + saline, PPAS, n = 10); and Group 3 (PPA + BSS, PPAB, n = 10). Treatments were administered for 15 days. Behavioral performance was assessed through three-chamber sociability, open field, and passive avoidance learning tests, followed by biochemical and histological evaluations of brain tissues. Biochemical analysis revealed a significant increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin-17 levels in the PPAS group, indicating heightened oxidative stress and inflammation. Treatment notably reduced these markers, suggesting its efficacy in mitigating oxidative damage and inflammatory responses. Immunohistochemical results demonstrated reduced glial activation and enhanced neuronal preservation in the hippocampal and cerebellar regions of treated rats. Additionally, behavioral impairments in social interaction, exploration, and memory were significantly improved with BSS therapy. These results suggest that BSS may confer neuroprotective effects through attenuation of oxidative stress and neuroinflammation, potentially contributing to improved neuronal function and behavioral performance in a PPA-induced autism model.

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14. Lecciso F, Martis C, Levante A. The Use of Griffiths III in the Appraisal of the Developmental Profile in Autism: A Systematic Search and Review. Brain Sci. 2025; 15(5).

BACKGROUND: Griffiths III is a child-friendly and play-oriented direct gold-standard measure of a 0-6-year-old child’s developmental profile. It is a measure that helps practitioners in detecting the weaknesses in children who have an increased likelihood or a diagnosis of neurodevelopmental disorders, e.g., autism. OBJECTIVES: Following the PICO protocol, two research questions addressed the current systematic search and review (Prospero registration: CRD42024554286): What is(are) the main developmental domain(s) evaluated by Griffiths III impaired in autism? (RQ1); Using Griffiths III, what is(are) the main developmental domain(s) improved after an autism-specific early intervention? (RQ2). METHODS: Six studies have been reviewed: three case-control studies, a case report study, and two studies examining the effectiveness of early autism-specific interventions. According to the study design, the methodological quality was evaluated using three standardised protocols: STROBE; JBI; CEC. RESULTS: The results highlighted that the Language and Communication and Personal-Social-Emotional domains are the most impaired in autistic children and in those with an increased likelihood (RQ1). The results outlined that early target intervention enhanced the same domains (RQ2). CONCLUSIONS: In conclusion, the findings highlight the importance of screening not only for autism traits but also for impairments in language, communication, and socio-emotional skills. The future direction of the results is discussed.

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15. Liu Y, Sun Y, Chen A, Chen J, Zhu T, Wang S, Qiao W, Zhou D, Zhang X, Chen S, Shi Y, Yang Y, Wang J, Wu L, Fan L. Involvement of disulfidptosis in the pathophysiology of autism spectrum disorder. Life Sci. 2025; 369: 123531.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder, with oxidative stress recognized as a key pathogenic mechanisms. Oxidative stress disrupts intracellular dynamic- thiol/disulfide homeostasis (DTDH), potentially leading to disulfidptosis, a newly identified cell death mechanism. While studies suggest a link between DTDH and ASD, direct evidence implicating disulfidptosis in ASD pathogenesis remains limited. In this study, Mendelian randomization analysis revealed a significant causal association between disulfidptosis-related sulfhydryl oxidase 1 and 2 and ASD (OR1 = 0.883, OR2 = 0.924, p < 0.05). A positive correlation between protein disulfide-isomerase and cognitive performance (OR = 1.021, p < 0.01) further supported the role of disulfidptosis in ASD. Seven disulfidptosis-related genes (TIMP1, STAT3, VWA1, ADA, IL5, PF4, and TXNDC12) were identified and linked to immune cell alterations. A TF-miRNA-mRNA regulatory network and a predictive model (AUC = 0.759) were constructed and external validation datasets (AUC = 0.811). Immune infiltration analysis demonstrated altered expression of naive B cells and three other types of immune cells in ASD children. Animal experiments further validated the differential expression of key genes, highlighting their relevance to ASD pathogenesis. Animal experiments found that BTBR mice exhibit glucose starvation and NADPH depletion, with the specific indicator Slc7a11 being highly expressed. Silencing Slc7a11 can improve core ASD impairments in BTBR mice. CONCLUSION: This study establishes the first mechanistic link between disulfidptosis and ASD, identifies seven key genes and their regulatory network, and develops a predictive model with clinical utility. Animal experiments further confirmed the strong association between disulfidpotosis and ASD phenotypes. These findings offer novel therapeutic targets for modulating oxidative stress in ASD.

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16. Montiel-Nava C, Navarro C, Abouchard J, Ramirez AC, Villareal V, Calderon R, Kantor SP, Neeley V, Allegre A, Pagán AF, Montenegro MC. Time to Listen: Engaging Latino Autistic Adults and Parents as Partners in Advancing Autism Research. J Autism Dev Disord. 2025.

The limited representation of Latino autistic individuals and their families in research studies limits our understanding of how autism presents and is experienced across diverse communities, emphasizing a need for more inclusive research methodologies and participant recruitment strategies. Our project aimed to explore how participatory research methods can be effectively implemented to develop culturally valid measurement tools and research protocols that accurately capture the experiences of bilingual/bicultural Latino autistic individuals and their families. This study used a phenomenological framework design guided by community-based Participatory research and the social model of disability principles. Two trained researchers conducted three focus groups with Latino parents of autistic children (n = 25) and two with Latino autistic adults (n = 8), and data was analyzed utilizing thematic analysis. We used a consultative model in which a community advisory board provided input throughout the project. Effective research engagement in border Latino communities is contingent on three key factors: fostering cultural and linguistic alignment, building and maintaining institutional trust, and thoughtfully incorporating community symbols. Together, these elements highlight a roadmap for researchers to build sustainable partnerships rooted in respect, equity, and cultural competence. Culturally informed research procedures, led by a culturally sensitive team of Latino researchers and Latino autism community members working as equal partners, can enhance engagement and ensure relevant, valid research studies and priorities. Using a CBPR framework and an intersectionality lens advances equitable representation in autism research and promotes culturally informed responses to the needs of diverse autistic communities.

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17. Mossa A, Dierdorff L, Lukin J, Garcia-Forn M, Wang W, Mamashli F, Park Y, Fiorenzani C, Akpinar Z, Kamps J, Tatzelt J, Wu Z, De Rubeis S. Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X. Nat Commun. 2025; 16(1): 4512.

DDX3X is an X-linked RNA helicase that escapes X chromosome inactivation and is expressed at higher levels in female brains. Mutations in DDX3X are associated with intellectual disability (ID) and autism spectrum disorder (ASD) and are predominantly identified in females (DDX3X syndrome). Using cellular and mouse models, we show that Ddx3x mediates sexual dimorphisms in brain development at a molecular, cellular, and behavioral level. During cortical neuronal development, Ddx3x sustains a female-biased signature of enhanced ribosomal biogenesis and mRNA metabolism. Compared to male neurons, female neurons display larger nucleoli, higher expression of a set of ribosomal proteins, and a higher cytoplasm-to-nucleus ratio of ribosomal RNA. All these sex dimorphisms are obliterated by Ddx3x loss. Ddx3x regulates dendritic arborization complexity in a sex- and dose-dependent manner in both female and male neurons. Ddx3x modulates the development of dendritic spines but only in female neurons. Further, ablating Ddx3x conditionally in forebrain neurons is sufficient to yield sex-specific changes in developmental outcomes and motor function. Together, these findings pose Ddx3x as a mediator of sexual differentiation during neurodevelopment and open new avenues to understand sex differences in health and disease.

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18. Neville-Jones R, Garvin T, Enticott PG, Fuller-Tyszkiewicz M, Kirkovski M. Neurocognitive Profiles in Parents of Autistic Children and Parents of Children with Anorexia Nervosa. J Autism Dev Disord. 2025.

There is growing evidence to suggest an overlap between autism spectrum disorder (autism) and anorexia nervosa (AN), both of which are known to be highly heritable conditions. The aim of this study was to explore overlapping behavioural and clinical characteristics, and neurocognitive profiles related to the autism dyad of symptoms among parents. Parents of autistic children, parents of children with AN, and parents of typically developing children completed a battery of behavioural questionnaires and neurocognitive tasks related to social cognition and cognitive flexibility. Parents of autistic children reported significantly more difficulties on imaginative abilities compared to the other two parent groups. Parents of children with AN had superior performance on cognitive flexibility tasks. As expected, and in support of an overlap between the two conditions, increased eating disorder psychopathology was associated with poorer performance on neurocognitive tasks related to the autism dyad. Understanding the overlap between AN and autism has important implications for accurate development of risk profiles, diagnosis, as well as treatment. This is critical as those with overlapping traits of autism and AN have poorer treatment outcomes and are at higher risk of the damaging physical health consequences of AN.

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19. Pokhrel P, Joshi S, Fatima L. Artificial intelligence in autism spectrum disorder: A path to early detection and improved outcomes. Asian J Psychiatr. 2025; 109: 104530.

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20. Postogna FM, Roggero OM, Biella F, Frasca A. Interpreting the rich dialogue between astrocytes and neurons: An overview in Rett syndrome. Brain Res Bull. 2025; 227: 111386.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females, with an incidence of 1 in 10,000 live births. It is caused mainly by de novo mutations in the X-linked MECP2 gene, which encodes methyl-CpG binding protein 2 (Mecp2), a key epigenetic regulator. MECP2 mutations have profound impacts on neurons, which exhibit morphological, synaptic and functional impairments. However, more recent evidence highlights a crucial role of astrocytes in RTT pathogenesis. Indeed, RTT astrocytes exhibit structural and functional impairments, failing to support neuronal growth and function through non-cell autonomous mechanisms. Studies reveal that MECP2 deficient astrocytes secrete abnormal factors that impair neuronal growth and synaptic function. Furthermore, they show dysregulated calcium signalling, disrupted glutamate and potassium homeostasis, and increased inflammatory responses, all of which contribute to neuronal dysfunction. Understanding these neuron-astrocyte interactions may offer novel therapeutic targets for RTT. In the review we aim at presenting the current knowledge of astrocyte-neuron crosstalk in RTT, describing the different mechanisms highlighted so far through which MECP2 mutant astrocytes impair neurons. Finally, we discuss existing and prospective methodological approaches for investigating cell-to-cell communication in RTT.

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21. Raj A, Ratnaik R, Sengar SS, Fredo ARJ. Characterizing ASD Subtypes Using Morphological Features from sMRI with Unsupervised Learning. Stud Health Technol Inform. 2025; 327: 1403-7.

In this study, we attempted to identify the subtypes of autism spectrum disorder (ASD) with the help of anatomical alterations found in structural magnetic resonance imaging (sMRI) data of the ASD brain and machine learning tools. Initially, the sMRI data was preprocessed using the FreeSurfer toolbox. Further, the brain regions were segmented into 148 regions of interest using the Destrieux atlas. Features such as volume, thickness, surface area, and mean curvature were extracted for each brain region. We performed principal component analysis independently on the volume, thickness, surface area, and mean curvature features and identified the top 10 features. Further, we applied k-means clustering on these top 10 features and validated the number of clusters using Elbow and Silhouette method. Our study identified two clusters in the dataset which significantly shows the existence of two subtypes in ASD. We identified the features such as volume of scaled lh_G_front middle, thickness of scaled rh_S_temporal transverse, area of scaled lh_S_temporal sup, and mean curvature of scaled lh_G_precentral as the significant features discriminating the two clusters with statistically significant p-value (p<0.05). Thus, our proposed method is effective for the identification of ASD subtypes and can also be useful for the screening of other similar neurological disorders.

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22. Randolph JK, Benigno J, Markollari MZ, Cheak-Zamora N. Reflections of Autistic Adults on Employment Preparation Programs: A Qualitative Analysis. J Occup Rehabil. 2025.

PURPOSE: Autistic adults face significant barriers to employment. While caregiver and provider perspectives have informed transition programming to address these barriers, limited research has gathered insights directly from autistic adults. This study aimed to explore the experiences of autistic adults who completed an employment preparation program to identify the unmet needs and evaluate the impact on employment outcomes. METHODS: Semi-structured interviews were conducted with 16 autistic adults and consisted of 26 core questions, allowing for an exploratory line of questioning. This method was chosen to address the gap in the literature regarding autistic adults’ direct experiences and needs. The interviews were analyzed using inductive thematic analysis, prioritizing participants’ words and experiences revealing novel insights into transition services. Demographic information and closed-ended questions were analyzed using descriptive statistics. RESULTS: Participants expressed overall satisfaction with the programs, and most were currently employed, attributing their job obtainment to the transition program. Thematic analysis revealed four primary themes: (1) Job Skills; (2) Job Experience and Coaching; (3) Peer Relationships; and (4) Goal Setting. Participants reported benefits such as improved job obtainment skills, on-the-job experience, peer socialization, and practice setting goals. However, challenges were identified, including difficulties in maintaining relationships with peers and concerns about excessive involvement by job coaches. CONCLUSION: The findings highlight the benefits and limitations of employment preparation programs for autistic adults. The insights gained can inform the development of future programs and the training of personnel aiming to enhance the effectiveness of services for autistic adults seeking employment.

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23. Rashid N, Darer JD, Ruetsch C, Yang X. Aspiration, respiratory complications, and associated healthcare resource utilization among individuals with Rett syndrome. Orphanet J Rare Dis. 2025; 20(1): 232.

BACKGROUND: Individuals with Rett syndrome (RTT) are at high risk for aspiration and also experience high rates of lower respiratory tract infections (LRTI) and respiratory failure (RF). METHODS: A retrospective comparative cohort analysis was performed among 89 individuals with RTT with and without evidence of aspiration, using EHR structured and abstracted clinical notes data. Individuals with known or suspected aspiration (per clinical documentation) (cases) were compared to controls on aspiration risk factors, RF, LRTI, and hospitalization. RESULTS: Of eligible individuals, 25 (28.1%) were aspiration cases. The cumulative rate of RF among RTT individuals with and without aspiration was 60.0% and 6.3%, respectively. Aspiration cases were more likely to have risk factors compared to controls during the 6-month baseline including epilepsy (54.5% vs. 4.5%), dysphagia (40.9% vs. 0%), GERD (31.8% vs. 0.0%), scoliosis (31.8% vs. 4.5%), and vomiting (18.2% vs. 0.0%). Aspiration cases were more likely to have LRTI (50% vs. 5.0%) and ≥ 1 inpatient admissions than non-aspiration controls (75.0% vs. 35.0%) (all p < 0.05). CONCLUSIONS: Individuals with RTT with known or suspected aspiration are at increased risk of LRTI, RF, and inpatient admissions. Providers should monitor aspiration and institute preventative measures among individuals with aspiration risk factors even in the absence of aspiration symptoms.

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24. Sugiyama M, Mori M. Sex differences in the relationship between autistic traits and face-change discrimination sensitivity in the general population: a psychophysical investigation. Cogn Process. 2025.

The findings on the effect of autistic traits on face recognition performance vary across previous studies. Even though people with higher autistic traits have difficulties identifying faces, the extent to which they have difficulties is unknown. Moreover, even though Autism Spectrum Disorder has sex differences in prevalence and symptoms, a limited number of studies consider sex differences in face recognition. The present study examined the relationship between face-change discrimination sensitivity and autistic traits considering sex differences. The participants included 82 females and 88 males in the general population. Face change blindness task using psychophysical method was used to evaluate the degree of sensitivity to faces in each participant. A psychometric function computed the Point of Subjective Equality (PSE) as the morphing level required to discriminate between faces. The Autism Spectrum Quotient (AQ) was also administered to participants. The results revealed a negative relationship between the total score of the AQ and the PSE in females but not males. This study suggests that sex differences should be considered when examining the relationship between autistic traits and other-face perception.

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25. Uljarević M, Chetcuti L, Loth E, Whitehouse A, Krueger R. Shaping the future of autism care: the need for a precision medicine approach. World Psychiatry. 2025; 24(2): 280-2.

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26. Warrick JE, Attili D, van Eeuwen T, Hoffmann-Weitsman SE, Forsyth NC, Barmada SJ, Kearse MG. An autism spectrum disorder mutation in Topoisomerase 3β causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain. bioRxiv. 2025.

The loss and mutation of Topoisomerase 3β (TOP3B), the only known eukaryotic topoisomerase with the ability to catalyze RNA strand passage reactions, is linked to schizophrenia, autism, and intellectual disability. Uniquely, TOP3B primarily localizes to the cytoplasm and has been shown to regulate translation and stability of a subset of mRNA transcripts. Three neurological disease-linked de novo TOP3B point mutations outside of the active site have been identified but their impact on TOP3B activity in cells remains poorly understood. Upon establishing a new Neuro2A cell-based TOP3B activity assay, we provide genetic and biochemical evidence that the autism-linked C666R mutation causes accumulation of unresolved TOP3B•mRNA covalent intermediates by directly disrupting metal coordination via an atypical D1C3-type metal binding motif within the zinc finger domain. Furthermore, we show that primary neurons are sensitive to high levels of TOP3B•mRNA covalent intermediates and that such adducts are capable of causing ribosome collisions. Together, these data identify a previously underappreciated role of the zinc finger domain and how non-active site disease-linked mutations affect TOP3B activity.

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27. Wu Z, Wu C, Chen X, Qian Q, Yao Z. Bidirectional Relationship Between Atopic Dermatitis and Psychiatric Comorbidities in Individuals of European Ancestry: A Mendelian Randomization Study. Acta Derm Venereol. 2025; 105: adv43133.

Atopic dermatitis is a chronic inflammatory skin disorder that significantly impacts quality of life and is often associated with psychiatric comorbidities. How-ever, the causal relationship between atopic dermatitis and psychiatric disorders remains unclear. This study employed bidirectional 2-sample Mendelian randomization to investigate the potential causal relationships between atopic dermatitis and 8 psychiatric conditions: depression, anxiety, autism spectrum disorder, attention deficit hyperactivity disorder, suicidality, bipolar disorder, obsessive-compulsive disorder, and schizophrenia. Genetic instruments were derived from large-scale genome-wide association studies of European ancestry. Forward Mendelian randomization analysis indicated that atopic dermatitis causally increases the risk of anxiety (inverse variance weighting p = 0.016; odds ratio = 1.110, 95% confidence interval: 1.019-1.208). Reverse Mendelian randomization analysis revealed a significant causal effect of bipolar disorder on increasing the risk of atopic dermatitis (inverse variance weighting p = 0.005; odds ratio = 1.062, 95% confidence interval: 1.018-1.107). No significant causal relationships were found for other psychiatric conditions. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy. These results highlight the need for integrated dermatological and psychiatric care, emphasizing early mental health screening for atopic dermatitis patients and dermatological evaluation for individuals with bipolar disorder. Future research should explore underlying biological mechanisms and validate findings across diverse populations.

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28. Yuen WY, Lim TSH, Karthik SV, Lim YY, Teo EM, Chan YH, Shen L, Mulay KV. Rising Rates of Obesity Amongst Children on the Autism Spectrum During the COVID-19 Pandemic. Nutrients. 2025; 17(10).

Background: The COVID-19 pandemic has been associated with rising obesity rates. Autistic children have a higher risk of obesity than neurotypical children. Our study aims to describe the changes in overweight/obesity rates in autistic children during the pandemic, and to identify contributing factors. Methods: This is a retrospective case record review of patients with a clinical diagnosis of autism, who were seen at a developmental-behavioral pediatrics clinic in a tertiary academic hospital, between 1 January 2019 and 24 October 2021. We compared the average monthly rates of overweight/obese status pre- and during the pandemic. We collected data on the patients’ and parents’ demographics, duration of screen time per day, degree of difficulties related to autism symptoms and cognition. We analyzed factors associated with being overweight/obese during the pandemic. Results: 1330 patient visits were included. The mean age was 45.4 months; 78% were male; 52% were Chinese. The average monthly rate of overweight/obese status increased by 1.8% during the pandemic (17.9% pre-pandemic; 19.7% during pandemic). Factors associated with being overweight/obese during the pandemic included: Malay ethnicity (OR 2.321, p < 0.01), developmental delay (OR 2.80, p < 0.01), and lower parental education level (father OR 1.73, p = 0.01; mother OR 1.63, p = 0.03). On multivariate analysis, only Malay ethnicity (OR 2.95, p = 0.01) was significant. Conclusions: Our study demonstrates a rising overweight/obesity rate amongst children with autism spectrum disorder during the pandemic. It also identified higher-risk patient profiles (Malay race, developmental delay, lower parental education). We hope this will facilitate the implementation of preventative health measures specifically supporting the high-risk children.

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