1. Alabdulaziz H, Alghamdi S, Alharbi KS, Alrashdi HRM, Al-Mutairi JS, Aljuhani FH. Maternal emotional distress, caregiving burden, and service access among mothers of children with autism spectrum disorder: a qualitative study. Front Psychiatry. 2026; 17: 1971477.

INTRODUCTION: Mothers raising children with autism spectrum disorder (ASD) may experience substantial emotional distress and caregiving burden, whilst family support andaccess to services can shape how these demands are managed. Yet in-depthqualitative evidence on these public mental health dimensions remains limited inSaudi Arabia. This study explored mothers’ experiences of raising a child diagnosedwith ASD. METHODS: Using a qualitative descriptive design informed by a contextualistposition, the study recruited ten mothers through a specialist autism centre inMadinah and the surrounding community. Trained female researchers, all registered nurses, conducted semi-structured interviews in Arabic, each lastingapproximately 60 to 90 minutes. Recordings were transcribed verbatim inArabic; a professional translator produced English transcripts, which a secondbilingual researcher checked before reflexive thematic analysis. RESULTS AND DISCUSSION: Seven interrelated themes captured the mothers’ accounts: diagnosis as an emotional rupture; disruption of daily life by behavioural challenges; learning to understand the child across communication barriers; the cumulative toll of continuous care; adaptation through acceptance, patience, and faith; family support as a buffer or added burden; and compensating for uneven service experiences. Mothersdescribed substantial emotional and caregiving demands, but their experiences varied according to family support and access to services. One account of comprehensive state support provided an important counter-case to the morecommon experience of costly or fragmented provision. The findings position maternal emotional distress and caregiving burden as public mental health concerns shaped by family, social, and service contexts. They support a public mental health response that links maternal mental health promotion with accessible, coordinated, and family-centred care.

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2. Berenguer C, Fuentes-Sáez C, Baixauli I, Andrés MEP, Gómez-García S. Impact of augmented reality on narrative-related outcomes in children with Autism Spectrum Disorder: a within-subject design. Front Psychol. 2026; 17: 1926566.

INRODUCTION: Autism Spectrum Disorder (ASD) is commonly associated with impairments in social communication, narrative abilities, and socio-cognitive functioning. This study explored whether augmented reality (AR) could enhance narrative production, comprehension, use of mental state language, and reading-related behaviors in children with ASD. METHODS: Fifteen children with ASD without intellectual disability participated in a within-subjects design in which they completed story retelling tasks under two counterbalanced conditions: a traditional paper-based format and a tablet-based format. Narrative performance was assessed through measures of microstructure, including productivity, lexical diversity, and syntax, as well as macrostructure indicators such as recall of main ideas. Oral comprehension and reading-oriented behaviors were also examined. RESULTS: Results showed that the AR condition significantly improved socio-cognitive and behavioral outcomes. Children produced a higher number of mental state terms and demonstrated greater attention, persistence, and engagement during the tasks. These findings suggest that AR can function as an effective scaffold that facilitates the explicit representation of internal states while increasing attentional involvement. DISCUSSION: Consequently, AR technology may represent a promising tool for improving language assessment and fostering social-cognitive development in children with ASD.

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3. Chen F, Kneifati-Hayek J, Zelin C, Wu D, Nguyen QM, Ta CN, Liu C, Wang K, Chung WK, Weng C. Characterizing Autism Phenotype Onset in the Electronic Health Records to Enable Age-Specific Screening. Autism Res. 2026: e70378.

Autism exhibits substantial phenotypic heterogeneity, yet age-dependent variation in phenotypic profiles and onset timing remains poorly understood. We aimed to characterize stage-specific phenotypes and temporal onset patterns of autism using longitudinal electronic health records (EHRs). We analyzed EHR data from Columbia University Irving Medical Center. Autism cases were stratified by age at diagnosis. Phenotype enrichment analyses were performed using chi-square and Fisher’s exact tests to identify phenotypes overrepresented in autism cases compared with matched controls, and temporal patterns of phenotype onset were subsequently evaluated to identify stage-specific clinical signatures and provide insight into differences between early- and late-diagnosed individuals. Among 4818 cases and 1433 phenotypes, 195 and 155 were enriched in toddlerhood and adolescence groups. Early diagnosed individuals exhibited a higher prevalence of sensory-related conditions, greater exposure to maternal and perinatal complications than their matched controls (all ORs > 1; p < 0.01), and earlier onset of neurologic features, including coordination abnormalities and convulsions, compared with later-diagnosed individuals. The study provides a publicly accessible resource to enrich autism-related phenotypic profiles, uncovering notable phenotypic differences and variations in timing of phenotype onset between early-diagnosed and later-diagnosed individuals. These findings underscore phenotypic heterogeneity and highlight the need for age-sensitive screening strategies. To our knowledge, this is among the first studies to jointly characterize phenotypic profiles and their temporal onset patterns across developmental stages in autism using longitudinal EHR data. These findings offer novel insights into age-dependent clinical signatures, informing earlier and more precise screening strategies.

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4. Hamlin T, Anderson C, Lantz JF, Franck J, le Roux Ohm H, Landry DW. Applying Lifestyle Medicine to Improve Health Outcomes in People With Intellectual and Developmental Disabilities. Am J Lifestyle Med. 2026: 15598276261486805.

Individuals with intellectual and developmental disabilities (I/DD) and autism spectrum disorder experience disproportionately high rates of chronic disease, often exacerbated by systemic care barriers. Despite these concerns, interventions for this population rarely target overall health and wellness and often rely on practices that can contribute to poor health outcomes. This retrospective review includes data collected at The Center for Discovery, a residential care program for people with severe and complex disabilities. This analysis evaluates health outcomes among 295 adults with I/DD, including autism, who received a comprehensive lifestyle medicine intervention. Prevalence rates of chronic conditions among those receiving the intervention were compared to national and New York State disability benchmarks. Results suggest an association with substantially lower prevalence of key conditions, including obesity, diabetes, and hypertension, with a median risk ratio of 0.325 (range: 0.23-0.76) compared to U.S. population benchmarks. These findings suggest that participation in an integrated lifestyle medicine model, SynergE6® Healthspan Model, could be associated with lower chronic disease prevalence among adults with I/DD. Because this was a retrospective observational study using external benchmark comparisons, prospective controlled studies are needed to determine whether these associations are causal.

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5. Heald BS, McKinney WS, Schmitt L, Dominick KC, Lacher RK, Piloto S, Gross C, Erickson CA. Association between FMR1 mRNA levels and clinical phenotypes in Fragile X syndrome. Res Sq. 2026.

Background Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene on chromosome X that leads to hypermethylation and reduces or completely silences the expression of FMR1 mRNA and its protein product, Fragile X Messenger Ribonucleoprotein (FMRP). Since the clinical manifestations of FXS can be variable, there is interest in identifying molecular markers that reflect phenotypic severity. The extent of CGG repeat expansion and resulting hypermethylation varies substantially between patients, suggesting that FMR1 gene silencing differs between individuals with FXS and could contribute to the phenotypic variability. Previous studies have identified FMR1 mRNA as a highly reproducible, sensitive and quantitative measure of gene activity. This study builds on these previous studies and assesses the relationship between FMR1 mRNA and clinical outcomes in FXS. Methods We recruited 300 study participants, including males and females across the following diagnostic groups: FXS, fragile X premutation carriers (PMCs), typically developing controls (TDC), and (non-FXS) developmental disability controls (DD). Peripheral blood samples were used for quantifying both FMR1 mRNA and FMRP (from a Luminex-based assay). IQ and adaptive behavior were evaluated with the Stanford-Binet 5 and Vineland-3 tests, respectively. Analyses examined group- and sex-level associations between FMR1 mRNA and FMRP, IQ, adaptive behavior, and age across diagnostic groups. Results FMR1 mRNA was substantially reduced in participants with FXS, particularly males, consistent with expected gene silencing. Within the FXS group, higher FMR1 mRNA levels were associated with higher IQ and better adaptive behavior. These associations were not observed in the TDC or DD comparison groups, suggesting that the relationship is specific to FXS pathology rather than developmental impairment more broadly. FMR1 mRNA also correlated positively with FMRP in FXS, supporting its validity as a molecular marker. Age-related increases in FMR1 mRNA were also observed in females with FXS. Conclusions Our findings that FMR1 mRNA correlates with both FMRP levels and clinical outcomes in participants with FXS support its utility as a clinically meaningful molecular marker of phenotypic severity. As an accessible surrogate of disease severity, FMR1 mRNA may help improve prognostic assessment and support more individualized treatment planning in FXS.

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6. Jung S, Richter JD. Dysregulation of FMR1 Splicing in Human Fragile X Syndrome. bioRxiv. 2026.

Fragile X Syndrome (FXS) is a neuro-developmental disorder caused by a CGG expansion in FMR1 , leading to transcriptional silencing and loss of the encoded protein FMRP. Surprisingly, ∼70% of FXS individuals express FMR1 , but the RNA is mis-spliced to isoform FMR1-217 , composed of exon 1 spliced to a pseudo-exon in intron 1 and cannot produce FMRP. Splice-switching ASOs rescue proper FMR1 splicing and restore FMRP. FMR1-217 mis-splicing increases with CGG repeat length and is negatively correlated with patient IQ. FMR1-217 is associated with ribosome footprints, indicating it is translated into a polypeptide that may impair cognition. R-loops form at the FMR1 locus and extend into the pseudo-exon, but splice-switching ASOs reduce FMR1-217 and elevate FMRP independently of R-loop formation. DRB-based transcription analysis identified impaired Pol II elongation at the 5′ region of FMR1 in FXS cells, indicated by accumulation of hypophosphorylated Pol II at the transcription start site. Consistent with this, camptothecin-induced Pol II stalling increased FMR1-217 pseudo-exon inclusion. The splicing factors PTBP1 and PTBP2 regulate FMR1-217 splicing in a differentiation stage-dependent manner. Together, these findings indicate that FMR1-217 mis-splicing in FXS is associated with CGG repeat expansion, R-loop formation, impaired co-transcriptional Pol II elongation and context-dependent regulation by PTBP1/PTBP2.

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7. Kakiuchi T, Yamamoto K, Imamura I, Hashiguchi K, Kawakubo H, Yamaguchi D, Fujioka Y, Okuda M. Gut Microbiota Composition in Helicobacter pylori-Positive Adolescents With Autism Spectrum Disorder: An Exploratory Compositional Analysis. Apmis. 2026; 134(10): e70271.

Alterations in the gut microbiota have been implicated in autism spectrum disorder (ASD), but reported microbial profiles remain inconsistent, potentially because of heterogeneity in factors affecting gut microbial composition. Because Helicobacter pylori infection is associated with alterations in the gut microbiota, we investigated whether ASD was associated with gut microbial composition in a cohort of H. pylori-positive adolescents. This cross-sectional study included seven adolescents with ASD and 80 controls before H. pylori eradication therapy. Gut microbiota was analyzed using 16S rRNA gene sequencing, with alpha diversity, centered log-ratio-transformed genus-level abundance, and overall community composition based on Aitchison distance evaluated between groups. No significant differences were observed in alpha diversity or overall microbial community composition. At the genus level, 82 genera met the prevalence criterion for individual testing, and no association remained significant after false-discovery-rate correction. The effect estimate for Roseburia was not statistically significant in either unadjusted or adjusted analyses. These findings do not support marked differences in overall gut microbiota composition associated with ASD within this H. pylori-positive cohort; however, the small ASD sample and substantial age imbalance limit the precision and interpretation of the findings.

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8. Khanday S, Darmaki AA, Malahifci R, Alvavi R, Ahmed S, Nasr DS. Gut microbiota and the gut-brain axis in autism spectrum disorder and attention-deficit/hyperactivity disorder: A scoping review of shared and disorder-specific mechanistic pathways. AIMS Microbiol. 2026; 12(3): 548-63.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are among the most prevalent neurodevelopmental conditions worldwide, yet the biological mechanisms driving their onset and phenotypic variability remain incompletely understood. The gut-brain axis (GBA), a bidirectional network linking intestinal microbial communities to central nervous system function through endocrine, immune, neural, and metabolic pathways, has emerged as a candidate mechanism through which environmental factors interact with genetic susceptibility to shape neurodevelopmental outcomes. OBJECTIVE: To systematically map the peer-reviewed evidence on gut microbiome-related mechanistic pathways in ASD and ADHD, we delineated features common to both disorders and identified areas of divergence and knowledge gaps requiring further investigation. METHODS: A scoping review was performed following the PRISMA Extension for the Scoping Reviews (PRISMA-ScR) framework. PubMed, Scopus, and Google Scholar were searched for peer-reviewed studies published January 2018 through March 2025. Studies addressing gut microbiome composition, GBA signaling, or microbiome-directed interventions in ASD or ADHD were eligible for inclusion. Extracted data were synthesized using inductive thematic analysis via Covidence software. RESULTS: Forty-five studies satisfied the eligibility criteria. Inductive analysis produced five mechanistic themes: Endocrine dysregulation and microbial metabolite signaling; neuronal signaling and neurotransmitter modulation; immune activation and neuroinflammation; gene-microbiota-environment interactions; and microbiota-targeted interventions. Studies on both disorders demonstrated modifications involving taxa with short-chain-fatty-acid-producing capacity; however, findings were varied and did not prove a common reduction in butyrate production. ASD was marked by pronounced dysregulation of the serotonergic system and tryptophan-kynurenine pathway and increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness. On the other hand, the results in ADHD were majorly cross-sectional or preliminary, and the widely-m recognized dopaminergic dysfunction in ADHD has not been associated to specific microbiota alterations to date. CONCLUSIONS: Evidence demonstrates the GBA as a useful research conceptual for investigating ASD and ADHD, although the strength of mechanistic evidence differs substantially between the two disorders. Translating these insights into therapeutic strategies will require longitudinal, multi-omic research designs capable of establishing causality and enabling patient stratification for precision microbiome-based interventions.

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9. McKenna F, Hemmerling KJ, Nandi S, Molholm S, Zhu DC. Multimodal MRI Clustering Reveals an Elevated Free-Water Biotype in Autism with Increased Social Symptoms. bioRxiv. 2026.

BACKGROUND: Autism spectrum disorder (ASD) is neurobiologically heterogeneous, and group comparisons may mask effects confined to subgroups. We tested whether distinct biotypes exist within ASD using unsupervised clustering of multimodal MRI. METHODS: We analyzed 149 participants with ASD and 129 typically developing (TD) controls from the Autism Brain Imaging Data Exchange II (6 sites; age 5 to 64 years). Site-harmonized features comprised free water (FW), tissue anisotropy and diffusivity, diffusion tensor image analysis along the perivascular space (DTI-ALPS), cerebrospinal fluid (CSF) volumes and exploratory resting-state regional homogeneity. ASD participants were clustered with k-means using global (7 features) and regional (17 features) sets, with robustness tested by permutation and two further algorithms. TD participants were projected post hoc to test specificity. A composite imaging score was related to Social Responsiveness Scale (SRS) subscales, symptom severity and IQ using partial correlations with false discovery rate correction. RESULTS: Clustering identified an elevated free-water (EFW) biotype comprising approximately 10% of ASD participants, defined by markedly increased FW (d = +4.91 versus remaining ASD participants), reduced tissue anisotropy, reduced DTI-ALPS and enlarged ventricles. It was recovered across feature sets and algorithms (permutation p < .0001) and departed from TD norms, unlike the remaining ASD participants. The composite score correlated with social-perceptual and communicative SRS subscales, most strongly social awareness (r = +0.253, q = .026), but not with symptom severity or IQ. FW related to social motivation in children and adolescents (r = +0.287, q = .037) but not adults. LIMITATIONS: Each person was scanned once, so we cannot tell whether these brain differences cause social difficulties or how they change with age. The subgroup was small, clinical data were incomplete, the sample was mostly male with a wide age range, and the findings await confirmation in an independent group. Free water can reflect inflammation, swelling or tissue loss, so its biological meaning remains uncertain. CONCLUSIONS: We identify an ASD subgroup defined by extracellular fluid excess and altered white matter that is associated with greater social difficulties. If replicated, this signature may help stratify individuals with ASD in mechanistic studies and clinical trials.

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10. Procacci NM, Debnath S, Das R, Bhraonain EN, Cobine CA, Gould TW. Neurogenic colonic motility patterns and gut transit disrupted in a mouse model of Rett Syndrome. bioRxiv. 2026.

Gastrointestinal dysfunction is a prominent feature of neurodevelopmental disorders and contributes significantly to visceral discomfort, but the specific etiology is unclear. In particular, it is unknown which cell types within central, autonomic or enteric nervous systems, gut muscle, epithelium or immune system are the principal drivers of gut dysfunction. We report that the Mecp2 mouse model of Rett syndrome, a neurodevelopmental disorder with profound gut dysmotility, exhibits impaired whole gut transit times and constipation in vivo as well as striking alterations to propagating neurogenic contractions in ex vivo colons. Selective elimination of Mecp2 in neurons, but not glia or smooth muscle, recapitulates these dysmotility phenotypes. Bulk RNA sequencing of colonic external muscle, containing the myenteric compartment of the enteric nervous system, showed significant expression changes in specific neurochemical signaling pathways. Pharmacological modulation of one, the M1 acetylcholine receptor, modified the aberrant neurogenic contractile phenotype in mutant mice and reproduced it in wild-type mice. These results identify disruptions to neuronal muscarinic signaling in the enteric nervous system in a mouse model of Rett syndrome and provide an experimental strategy to identify translationally relevant cellular and molecular pathways underlying gastrointestinal dysmotility in neurodevelopmental disorders.

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11. Qing Z, Yin Z, Chen B, Rao Z, Yin D, Li D, Lu Y, Shi M, Li S, Xu Y, Cheng K, An W, Yuan C, Dai Q. Biological hierarchy from genotype to phenotype in syndromic and non-syndromic autism spectrum disorder. Front Neurosci. 2026; 20: 1964684.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition whose pathophysiology is thought to arise from complex interactions among genetic variation, molecular and cellular perturbations, and neural circuit dysfunction. Although the distinction between syndromic and non-syndromic ASD was introduced as a pragmatic clinical classification, these clinically defined subgroups may exhibit overlapping yet distinct patterns of genetic liability and molecular dysregulation while also exhibiting mechanistic convergence. This narrative review examines the molecular mechanisms underlying synaptic development, structure, and function, with particular emphasis on the roles of chromatin remodeling and epigenetic regulation in neurodevelopment. It further considers how molecular and cellular alterations may contribute to impaired functional integration at the neural circuit level. By comparing the shared and unique genes and pathways associated with syndromic and non-syndromic ASD, the review identifies potential points of mechanistic convergence across multiple levels of biological organization. To integrate these findings, the review proposes a three-layer hierarchical framework that links gene function (Layer 1), core biological pathways (Layer 2), and clinical phenotypes (Layer 3). By mapping ASD-associated genes onto a functional continuum ranging from local synaptic effectors to global regulators of chromatin and gene expression, this framework illustrates how subtype-enriched genetic factors may give rise to both shared and unique molecular, cellular, and circuit-level alterations. The proposed framework may help identify common and subtype-enriched biological mechanisms, inform biomarker discovery, and provide a conceptual basis for mechanism-informed ASD research and biologically grounded clinical stratification.

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12. Shi T, Zhan X, Kuang Z, Lai H, Zeng L, Wang B, Peng X, Li X. Effects of exergames on children and adolescents with autism spectrum disorder: a scoping review. Child Neuropsychol. 2026: 1-35.

Exergaming, a form of sports entertainment game that integrates human‑computer interaction, motion sensing, virtual reality, and other high‑tech technologies, has been employed in the rehabilitation of children and adolescents with autism spectrum disorder due to its safety and low cost. However, the specific efficacy of implementing exergaming currently lacks systematic synthesis. This study, based on the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY), conducts a scoping review of intervention protocols, effectiveness, and health benefits of exergaming applied to children and adolescents with autism spectrum disorder, and synthesizes the characteristics of practical outcomes. Following the PRISMA-ScR guidelines, experimental studies on exergaming interventions for children and adolescents with ASD (aged 0-18 years) were retrieved from PubMed, Web of Science, EBSCO, EMBASE, and CINAHL databases, covering the period from 2010 to 2025. Health outcomes of the included studies were coded and analyzed based on the ICF-CY framework. A total of 28 studies (involving 12 countries and 789 participants) were included. Exergaming intervention protocols were characterized by diversity and individualization, showing improvements in multiple indicators among children and adolescents with ASD. A total intervention duration of less than 4 h was sufficient to produce beneficial effects, with sports simulation games being the most effective type of exergaming. Among the 77 outcome indicators, 52 are focused on body functions, 18 on activities and participation, and 7 on environmental factors. Exergaming is an effective non-pharmacological treatment. Future research should delve deeper into the dose-response relationship between intervention frequency and outcomes.

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13. Wirtjes JW, Willbrand EH, Weiner KS. The superior temporal asymmetrical pit remains asymmetric in autism spectrum disorder. bioRxiv. 2026.

Neuroimaging studies identify the superior temporal sulcus (STS) as an anatomical and functional target in autism spectrum disorder (ASD). Yet, the STS is a heterogeneous structure containing unique subregions, such as the superior temporal asymmetrical pit (STAP), which is a recently identified human-specific landmark. To date, no study has compared the STAP between ASD individuals and neurotypical controls (NTs) in a large sample. Here, we analyzed the mean intra-hemispheric sulcal depth and inter-hemispheric laterality of the STAP, as well as the anterior and posterior portions of the STS (aSTS, pSTS), in 100 NTs and 100 ASD male individuals (ages 5-18) using a discovery-replication design. Across samples, the STAP and pSTS showed rightward asymmetry, while the aSTS showed leftward asymmetry within groups. All features of the STAP, aSTS, or pSTS did not differ significantly between groups. However, pSTS laterality related to individual differences in social cognition, which was further supported by a meta-analysis across over 200 studies showing that neurocognitive functional differences associated with social cognition and ASD are restricted to portions of the STS outside of the STAP. Together, these findings provide fine-grained insight into prior studies showing coarse morphological differences of the STS between individuals with ASD and NTs, as well as open up new questions and new neuroanatomical targets of the heterogeneous STS in future studies of brain structure, brain function, and cognition in ASD, as well as other neurodevelopmental disorders targeting the superior temporal cortex.

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