1. Chen W, Wang X, Zhu R, Gao W, Tao L, Yang R, Wei Q, Zhang Y, Gong Y, Zhong H, Huang L, Zhu X, Yang Y, Zhang L, Wan L, Yang G, Li Y, Jiao N, Wang J, Qin H, Zhu L. Integrative multi-omics reveals microbial genomic variants driving altered host-microbe interactions in autism spectrum disorder. Cell Rep Med. 2025: 102516.

Emerging evidence links the gut microbiome to autism spectrum disorder (ASD), yet the role of microbial genomic variation remains underexplored. We generated a large-scale metagenomic and metabolomic dataset from over 1,100 children, integrating public datasets, to characterize ASD-associated microbial changes. We identified 35 species, 213 genes, 28 pathways, and 99 metabolites, alongside 1,369 single-nucleotide variants, 233 insertions/deletions, and 195 structural variants with differential abundance. Profiling of microbial genomic variation revealed 33 species and 196 enzymes lacking abundance differences, yet exhibiting significant sequence variation. Integrated analysis of microbial variants and metabolites uncovered 357 neurological associations, with mediation analysis showing that several metabolites link microbial variants to the ASD phenotype. Importantly, diagnostic models incorporating microbial variant and/or metabolite features achieved superior performance and generalizability. Our findings highlight microbial genomic variation as a critical, previously overlooked dimension of ASD-associated dysbiosis, offering valuable insights for diagnosis and mechanistic studies.

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2. Duieb O, Rezqaoui A, Boumlah S, Ibouzine-Dine L, Mallouk H, Ed-Day S, Elhessni A, Mesfioui A. Environmental enrichment partially rescues neurodevelopmental milestone delays in the prenatal VPA rat model of autism spectrum disorders. Behav Brain Res. 2025; 500: 116003.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by early sensorimotor delays, which often precede core social deficits as well as restricted and repetitive behaviors. Environmental enrichment (EE) is a promising behavioral intervention for ASD; however, its potential to prevent these earliest neurodevelopmental disruptions remains unexplored. This study investigated whether sustained EE could prevent early milestone delays in a prenatal valproic acid (VPA) rat model of ASD. Female Wistar rats were housed in standard (SH) or EE conditions for eight weeks, beginning two weeks before conception and continuing through lactation. Dams received a single injection of VPA (500 mg/kg) or saline on gestational day 12.5. Offspring were assessed daily from postnatal day (PND) 1-21 for the acquisition of physical and sensorimotor milestones. EE significantly mitigated VPA-induced delays in a subset of key neurodevelopmental milestones. While EE did not fully normalize development to control levels, a composite neurodevelopmental score revealed that EE significantly attenuated the global impairment induced by VPA. These findings demonstrate that preconception-perinatal EE confers partial protection against functional neurodevelopmental deficits in a predictive ASD model, highlighting its potential as a preventive strategy targeting the earliest manifestations of neurodevelopmental disruption.

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3. Ford TJ, Jeon BT, Lee H, Kim WY. Autism-like behavior Increases with age and is predated by molecular changes in Arid1b haploinsufficient mice. Neuroscience. 2025.

Genetic studies have revealed that ARID1B haploinsufficiency leads to autism spectrum disorder (ASD). Given the dynamic development of the brain and behavior, understanding the critical developmental window that influences the onset and severity of ASD-like behavior linked to ARID1B haploinsufficiency is important. Using an Arid1b haploinsufficient mouse model of ASD, we investigated age-dependent ASD-like behaviors at postnatal days 30, 60, and 120. We found that while wild type mice exhibited maturation of social and anxiety-like behaviors over the developmental window, Arid1b haploinsufficient mice showed no progression in the maturation of these behaviors. We also examined oxytocin expression in various brain regions across different developmental stages. Oxytocin mRNA levels in different brain regions were downregulated in Arid1b haploinsufficient mice throughout development and remained reduced with age. Finally, we explored corticosterone expression in Arid1b haploinsufficient mice to determine whether the allostatic regulation between oxytocin and corticosterone is altered in the context of social threat. Both wild type and Arid1b haploinsufficient mice displayed elevated corticosterone levels after social threat. However, Arid1b haploinsufficient mice showed significantly higher corticosterone and lower oxytocin levels than controls, suggesting disrupted allostatic regulation between oxytocin and corticosterone in Arid1b haploinsufficient mice. Our results show that the Arid1b haploinsufficient condition impairs the maturation of social and anxiety-like behaviors associated with ASD, with molecular alterations preceding behavioral deficits in this condition.

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4. Kotowska-Bąbol M, Konowałek Ł, Szajewska H, Łukasik J. Effect of multispecies probiotics on autism symptoms: protocol for a randomized controlled trial (PROBAUT). Trials. 2025.

INTRODUCTION: Autism spectrum disorder (ASD) affects millions of children worldwide, negatively impacting the daily functioning and quality of life of patients and their families. New therapeutic approaches for ASD are being investigated. Probiotics have shown promise in modulating gut microbiota and ameliorating ASD symptoms. We aim to evaluate the impact of a 12-week multispecies probiotic supplementation on the severity of core autism symptoms in children with ASD. METHODS AND ANALYSIS: This study is a randomized, double-blind, placebo-controlled clinical trial. One hundred and 10 children aged 7 to 15 years diagnosed with ASD will be randomly assigned in a 1:1 ratio to receive either a probiotic mixture or a placebo for 12 weeks. The probiotic mixture contains 5 × 10(9) colony-forming units per dose of Bacillus subtilis W20, Bifidobacterium infantis W17, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus rhamnosus W140, Lactococcus lactis W19, and Propionibacterium freudenreichii W200. The primary outcome will be the assessment of core autism symptoms using the Autism Symptom Rating Scales (ASRS). The secondary outcomes will include the quality of life, evaluations of sleep impairments, parental stress levels, gastrointestinal symptoms, and urinary p-cresol levels. These outcomes will be assessed twice: at baseline and after 12 weeks of intervention. ETHICS AND DISSEMINATION: The study has received approval from the Ethics Committee of the Medical University of Warsaw. Results will be submitted to a peer-reviewed journal and presented at national and international scientific meetings. TRIAL REGISTRATION: NCT06448767. Registered on 3 June 2024 Protocol version Version 2, 27 of October 2025.

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5. Sertié AL, Josino R, Goll VR, Nunes Goussain Filippo AL, Campos GDS, do Rego F, Siqueira ES, Farias de Alcântara N, Zachi EC, Passos-Bueno MR. Catatonia and regression in an autism spectrum disorder patient harbouring a BRSK2 frameshift mutation. J Med Genet. 2025.

Deleterious variants in the BRSK2 gene, which encodes a serine/threonine kinase crucial for neuronal polarisation and brain development, have recently been linked to the pathogenesis of autism spectrum disorder (ASD). However, comprehensive clinical descriptions of individuals with pathogenic BRSK2 variants remain limited, and the molecular and cellular consequences of these mutations are poorly understood. This case report provides a detailed clinical, cognitive and molecular characterisation of a male patient with ASD harbouring a de novo BRSK2 frameshift variant, who developed catatonia, developmental regression and cognitive decline during early adolescence. To assess the functional impact of the variant, induced pluripotent stem cells (iPSCs) and iPSC-derived neural organoids were generated from the patient. Molecular analyses revealed a significant reduction in BRSK2 transcript and protein levels. Sequencing of BRSK2 mRNA showed exclusive expression from the wild-type allele, consistent with degradation of the mutant transcript via nonsense-mediated decay. These findings broaden the mutational and phenotypic spectrum associated with BRSK2-related neurodevelopmental disorders and provide functional evidence supporting the pathogenicity of the identified variant. Furthermore, this report demonstrates the role of BRSK2 in complex neuropsychiatric features-such as catatonia and cognitive deterioration, which remain underreported in the existing literature-and emphasises the importance of longitudinal cognitive and behavioural monitoring in individuals with BRSK2 mutations.

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6. Towler JR, Kannan C, Soupioni C, Castle E, Fletcher-Miles H, Childs M, Donnelley S, Reinert-Joensen T, Brooks D, Tree JJ. Facial expression recognition in the broader autism phenotype: What does alexithymia have to do with it?. Cognition. 2025; 270: 106407.

Emotion recognition difficulties are widely reported in autism, but the « alexithymia hypothesis » proposes that such deficits are driven by co-occurring alexithymic traits rather than autism itself. We tested this hypothesis in a large sample of 556 adults spanning the broader autism phenotype, using self-reported autistic traits (Autism Quotient, AQ), alexithymia (Toronto Alexithymia Scale, TAS-20), and multiple face processing tasks. All participants completed an emotional expression discrimination task; Subsample 1 (N = 231) additionally completed an expression labelling task and Raven’s matrices, while Subsample 2 (N = 325) completed the Cambridge Face Memory Test. Across correlational, regression, partial correlation, and mediation analyses, autistic traits-particularly social-communicative difficulties-were the strongest and most consistent predictors of poorer emotion recognition. In contrast, the core alexithymia facets of difficulty identifying and describing feelings did not contribute unique variance once autistic traits were controlled. Importantly, externally oriented thinking (EOT) emerged as the only alexithymia facet with independent predictive value, consistently associated with reduced accuracy across both emotional and identity face recognition tasks. This suggests that EOT reflects a broader domain-general attentional style that deprioritises reflective engagement with socially salient information. Group-based analyses further confirmed that high autistic trait groups showed significant recognition impairments regardless of alexithymia levels. These findings challenge the alexithymia hypothesis and highlight autistic traits as primary drivers of emotion recognition difficulties, with EOT adding an additional, qualitatively distinct influence. The results call for revised multivariate models of face and emotion processing that integrate autistic traits, attentional orientations, cognitive ability, and gender.

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7. Wang X, Zeng C, Wu Z, Lu M, Wang X, Xiu Y, Wang Q, Wang S, Chen X, Shen Y, Li H, Su Y, Chen P, Chen H, Sheng N, Mo W, Yi C, Yang Q, Verkhratsky A, Niu J, Xiao L. Chromatin remodeling factor BAF155 coordinates oligodendroglial-neuronal communications linked to regional myelination and autism-like behavioral deficits in mice. Nat Commun. 2025.

Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with synaptic deficits. Oligodendrocyte precursor cells (OPCs) are the only type of glial cells that establish direct synaptic connections with neurons within the central nervous system (CNS). However, the mechanism that results in the delicate construction of OPC-neuron synaptic connections remain poorly understood. Here we show in a mouse model that BAF155, a chromatin remodeling factor, is highly expressed in committed OPCs. BAF155 influences the OPC differentiation and myelination by coordinating the expression of multiple synapse-related genes that mediate OPC-neuron synaptic communication. The varying chromatin regulatory roles of BAF155 across brain regions give rise to local myelin deficits, contributing to the diverse clinical manifestations observed in individuals with ASD. Collectively, these results deepen our insight into OPC-neuron interactions under pathophysiological conditions and uncover a mechanism that integrates synaptic and ASD susceptibility genes, implying that abnormal OPC-neuron synaptogenesis could be an early instigator of ASD.

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8. Xin Y, Yang Y, Qian Q, Xia T, Zhang W, Dai T, Li R, Liu Z, Zhang C. A pilot study of the plasma and urinary neurotransmitters in Chinese children with autism spectrum disorder. BMC Psychiatry. 2025.

BACKGROUND: Recent studies have indicated that there are imbalances in neurotransmitter levels in children with autism spectrum disorder (ASD). Alterations in peripheral blood and urinary neurotransmitter levels may serve as biomarkers for ASD. METHODS: This study aims to explore the relationship between neurotransmitter levels and the severity of ASD. Totally, forty sex-, age-, and ethnically matched typically developing (TD) children were recruited to compare the neurotransmitter levels with ASD aged over 3 years. Differences in plasma and urinary neurotransmitter levels between TD children and children with ASD were compared using the Mann-Whitney U test. For the indicators that showed significant differences, further multivariate regression analysis was conducted to assess the association between individual neurotransmitters and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Calibrated Severity Score (CSS). Finally, a restricted cubic spline (RCS) model was applied to explore the dose-response relationship between neurotransmitter concentrations and ADOS-2 CSS. RESULTS: Plasma levels of dopamine (DA), normetanephrine (NMN), 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (γ-GABA) levels in ASD were significantly higher than those in TD children while plasma levels of norepinephrine (NE), tyrosine (Tyr) were significantly lower. Urinary levels of NMN were significantly lower, while epinephrine (E), NE, vanillylmandelic acid (VMA), homovanillic acid (HVA) were significantly higher in children with ASD compared to TD. After adjusting for confounders of age, sex and BMI, plasma GABA was negatively associated with ADOS-2 CSS, while urinary NE and NMN were positively associated with ADOS severity scores (P ＜ 0.05). Multiple regression analysis indicated that plasma GABA and urinary NE and NMN levels explained 26.9%, 24.8% and 15.8% of the variability in ADOS-2 CSS for ASD. The RCS analysis results were largely consistent with the linear regression analysis results. Plasma GABA and urinary NE, and NMN exhibited a linear correlation with ADOS-2 CSS. Plasma NE and Tyr showed a U-shaped curve relationship with the ADOS-2 CSS (P<  0.05). CONCLUSIONS: A significant negative correlation was observed between plasma GABA neurotransmitter concentrations and ASD severity. In contrast, NE and NMN levels in urine showed significantly positive correlations with ASD severity. Both excessively low and excessively high plasma NE and Tyr levels may be associated with more severe autism symptoms, suggesting a disruption in peripheral neurotransmitter levels in children with ASD. Future studies with larger sample sizes are required for prediction and validation. The peripheral neurotransmitters may serve as potential auxiliary biomarkers for assessing the severity of autism.

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