1. BSPD issues oral health guide to support parents and carers of autistic children. Br Dent J;2025 (Jul);239(1):13.

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2. Al Mogren M, Teniou A, Rhouati A, Thakur A, Alanazi S, Anasori B, Zourob M. Integration of Ti(3)C(2)T(x) MXene in the selection of DNA aptamers for FMRP for the diagnosis of fragile X syndrome. Int J Biol Macromol;2025 (Jul 12):145968.

Being the second cause of intellectual disability after Down syndrome, Fragile X Syndrome (FXS) is a X-linked heritable disease. It is caused by a mutation in FMR1 gene consisting of an expansion of CGG repeats causing the absence or reduced expression of Fragile mental retardation protein (FMRP). FXS diagnosis is thus based on molecular techniques studying the FMR1 gene alterations. However, studying the protein is crucial for a better understanding of the FMRP role in brain development and function. This work aims to select a ssDNA aptamer for the detection and quantification of FMRP in blood. SELEX (Systematic Evolution of Ligands by EXponential enrichment) process, with a total of eight rounds of selection, was used to generate three ssDNA sequences able to bind FMRP. Affinity studies were performed by exploring the ability of ssDNA to adsorb to the titanium carbide (Ti(3)C(2)T(x)) MXene. Dissociation constants were determined based on the capacity of MXene to quench the fluorophore labeling of the aptamers. The aptamer sequence FM1, with the best affinity K(d) = 25.35 nM, was employed for the design of a fluorescent assay, where Ti(3)C(2)T(x) MXene acts as an energy acceptor. Under the optimal conditions, the proposed strategy enabled the FMRP determination within the range of 0.01 to 1000 ng/mL and the low detection limit of 0.038 pg/mL. MXene-based aptamer selection could be an excellent alternative in SELEX to techniques used in traditional SELEX.

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3. Bertilsdotter Rosqvist H, Pearson A, Pavlopoulou G, Bottema-Beutel K. The social model in autism research. Autism;2025 (Jul 12):13623613251357648.

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4. Choi JW, Parenti M, Slupsky CM, Tancredi DJ, Schmidt RJ, Shin HM. Maternal serum and placental metabolomes in association with prenatal exposure to per- and polyfluoroalkyl substances and their relevance to child neurodevelopment in an ASD-enriched cohort. Environ Pollut;2025 (Jul 9);383:126811.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to altered neurodevelopment in children, but the contribution of maternal metabolic disruption to this relationship remains unclear. We investigated associations between prenatal PFAS exposure, maternal metabolism, and child neurodevelopment. We analyzed 172 mother-child pairs from the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Nine PFAS were measured in maternal serum collected during pregnancy. Metabolites were quantified in third-trimester serum and placental tissue using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. At age three, children were clinically classified as having autism spectrum disorder (ASD), typical development (TD), or non-typical development (non-TD), the latter including children with atypical developmental features who do not meet the criteria for ASD. Multiple linear regression assessed associations between individual PFAS and metabolites, and quantile-based g-computation evaluated PFAS mixture effects. Principal component analysis (PCA) summarized metabolomic profiles. One-way analysis of covariance (ANCOVA) and multinomial logistic regression examined associations between metabolites and child neurodevelopment. Correlation network analysis explored relationships among PFAS, serum, and placental metabolites. After multiple comparison correction, perfluorooctane sulfonate (PFOS) was significantly associated with serum 2-hydroxybutyrate (q < 0.10). Higher perfluorooctanoate (PFOA), PFOS, and PFAS mixture levels were associated with lower serum PC-2 scores. Higher serum PC-3 score, reflecting mitochondrial dysfunction, was associated with increased non-TD risk. Network analysis identified 2-hydroxybutyrate as a key serum metabolite potentially linked to PFAS and placental amino acids. Prenatal PFAS exposure was associated with maternal metabolic alterations; however, no clear linkage to child neurodevelopment were observed. These findings suggest the need to consider gene-environment interactions in studies of neurodevelopmental outcomes.

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5. Hu C, Li H, Cui J, Li Y, Zhang F, Li H, Luo X, Hao Y. Integrative analysis identifies IL-6/JUN/MMP-9 pathway destroyed blood-brain-barrier in autism mice via machine learning and bioinformatic analysis. Transl Psychiatry;2025 (Jul 11);15(1):239.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and restricted, repetitive behaviors. Growing evidence implicates neuroinflammation-induced blood-brain barrier (BBB) dysfunction as a key pathogenic mechanism in ASD, although the underlying molecular pathways remain poorly understood. This study aimed to identify critical genes linking BBB function and neuroinflammatory activation, with the ultimate goal of evaluating potential therapeutic targets. Through integrative analysis combining differential gene expression profiling with three machine learning algorithms – Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and RandomForest combined with eXtreme Gradient Boosting (XGBoost) – we identified four hub genes, with JUN emerging as a core regulator. JUN demonstrated strong associations with both BBB integrity and microglial activation in ASD pathogenesis. Using a maternal immune activation (MIA) mouse model of ASD, we observed significant downregulation of cortical tight junction proteins ZO-1 and occludin, confirmed through immunofluorescence and qPCR analysis. Bioinformatics analysis revealed a close correlation between JUN and IL-6/MMP-9 signaling in ASD-associated microglial activation. These findings were validated in vivo, with immunofluorescence and qPCR demonstrating elevated IL-6 and MMP-9 expression in ASD mice. Pharmacological intervention using ventricular JNK inhibitor administration effectively downregulated JUN and MMP-9 expression. In vitro studies using IL-6-stimulated BV-2 microglial cells replicated these findings, showing JNK inhibitor-mediated suppression of JUN and MMP-9 upregulation. These results collectively identify the IL-6/JUN/MMP-9 pathway as a specific mediator of barrier dysfunction in ASD, representing a promising target for personalized therapeutic interventions.

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6. Joshi S, Lnb S. An ensemble classifier for emotion classification from EEG and GSR signals for autism detection. Comput Methods Programs Biomed;2025 (Jun 19);270:108921.

Determining individuals’ psycho physiological states is essential in multiple fields, especially for integrating disabled individuals into social environments. Among these pursuits, the domain of autism detection emerges as an important area of concern. In this context, the importance of leveraging distinct physiological signals for emotion recognition becomes evident. Traditional methods relying largely on posture and facial expressions have shown limited success for achieving the desired accuracy in emotion recognition. To address these limitations, recent research has turned towards exploring a diverse array of physiological signals. Electroencephalogram (EEG) and Galvanic Skin Response (GSR) signals have come to the forefront due to their ability to offer more nuanced insights into the emotional states of individuals. However, very few works have been reported on the fusion of multimodal signals in this aspect. Therefore, this paper proposes an Ensemble Classifier for Emotion Classification from EEG and GSR Signals for Autism Detection (ECE-AD). This model called the Emotion Classification Ensemble for Autism Detection (ECE-AD) is intended to capture longer range dependencies and contextual information from data sequences for accurate emotion classification. It is built as a multiclass classifier and evaluated on a public dataset achieving 99.97 % detection accuracy, 99.31 % sensitivity, 99.99 % specificity and 0.9870 % precision. The ECE-AD showcases robustness suitable for clinical integration in emotion detection and enhancing the quality of care within healthcare settings.

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7. Kalingel Levi M, Granovsky Y, Weissman-Fogel I, Shalita TB, Hoffman T, Gal E. Development and Validation of the Pain Awareness Scale (PAS) for Autistic Adults: A Mixed-Methods Study. J Pain;2025 (Jul 9):105491.

This study aimed to develop and validate the Pain Awareness Scale (PAS), a novel self-report questionnaire designed to assess pain awareness in autistic adults. Using a mixed-methods approach, the PAS was developed through literature review, expert consultation, and cognitive interviews with nine autistic adults (5 females, mean age= 29.1, SD= 7.9). The questionnaire was then administered to 59 autistic (24 females, mean age=26.8, SD=7.4) and 73 neurotypical adults (19 females, mean age=27.8, SD=6.7). Principal Axis Factoring revealed four distinct subscales: Pain Recognition, Pain Characterization, Nonverbal Pain Communication, and Verbal Pain Communication. The PAS demonstrated good internal consistency across all subscales (Cronbach’s α=0.71-0.92) and strong construct validity, with autistic adults scoring significantly higher than neurotypical adults’ total score and on three out of four subscales (p < 0.001). Convergent Validity was supported by significant correlations between the PAS and the Toronto Alexithymia Scale-20 (TAS-20) total scores (ρ= 0.69, p< 0.01). The PAS offers a reliable and valid tool for assessing pain awareness difficulties in autistic adults. PERSPECTIVE: This article introduces the Pain Awareness Scale (PAS), a psychometrically validated measure of pain awareness in autistic adults. The PAS may enhance clinical assessment and deepen understanding of pain processing differences in autism, offering insight into underlying mechanisms relevant for both clinical and basic science research.

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8. Li L, Huang Q, Hu J, Jin M, Zhuo Y, Ke W, He Q, Xiao Y, Zhang X, Wang W, Cheng TL, Tai Y, Guo F, Yu J, Yulong L, He J, Li B, Shu Y. Selective loss of Scn2a in ventral tegmental area dopaminergic neurons leads to dopamine system hypofunction and autistic-like behaviors. Neuron;2025 (Jul 7)

Dopamine hypothesis has been proposed as a mechanism of autism spectrum disorder (ASD), a neurodevelopmental disorder closely associated with genetic mutations. Loss-of-function mutation of SCN2A, which encodes the voltage-gated Na(+) channel Na(V)1.2, is a high risk factor for autism, but whether its pathogenesis is attributable to dopamine system dysfunction remains unclear. Here, we found that Scn2a is the predominant isoform and contributes largely to Na(+) currents along the somato-axonal axis of dopaminergic neurons (DANs) in mouse ventral tegmental area (VTA). Complete deletion of Scn2a in VTA DANs reduces their spiking activity and dopamine release, leading to hyperactivity, impaired sociability, and insufficient anxiety. Similar alterations were observed in Scn2a heterozygous mice. Importantly, acute treatment with levodopa alleviates non-motor behavior deficits. Together, the results reveal that Scn2a loss in VTA DANs alone causes autistic-like behaviors through a dopamine-hypofunction mechanism and also provide a possible pharmacotherapy through dopamine replacement for ASD with SCN2A mutations.

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9. Marsicano G, Garofalo S, Ronconi L, Bertini C. Autistic and schizotypal traits influence audiovisual temporal binding window malleability following alpha-band entrainment. Biol Psychol;2025 (Jul 12);199:109082.

The likelihood of integrating audiovisual (AV) information is reflected in the construct of temporal binding window (TBW), which accounts for the differing processing times across sensory regions. Wider TBWs within the autistic and schizotypal spectrums predict the degree of cognitive-perceptual and socio-communicative atypicalities. Alpha oscillations (8-13 Hz) represent an important neural mechanism for AV binding, and consequently alpha-band entrainment can shrink or expand TBWs. However, whether interindividual differences in autistic and schizotypal traits influence TBW modulations under entrainment is unexplored. Here, we used alpha-band sensory AV entrainment to explore how individual traits affect TBW malleability in neurotypical individuals (n = 113), administering rhythmic stimulations at slower (∼8.5 Hz) and faster alpha (∼12 Hz) frequencies before an AV simultaneity judgement task. Participants self-reported autistic and schizotypal traits, and a cluster analysis stratified individuals into three groups: high Cognitive-Perceptual Traits (CPT), high Socio-Affective Traits (SAT), Low Traits (LT). Results revealed that, across groups, upper alpha entrainment narrowed TBWs, enhancing AV temporal acuity. However, following lower alpha stimulation, only the CPT group exhibited wider TBWs, indicating a heightened responsiveness to entrainment stimulation, reflecting bottom-up atypical integration of sensory information into coherent models. Additionally, the typical leading sense asymmetry determining narrower TBWs for auditory-leading sequences was observed only in the LT group, suggesting that even sub-clinical cognitive-perceptual and socio-communicative atypicalities may disrupt basic aspects of cross-modal interactions. These findings suggest that socio-communicative and cognitive-perceptual anomalies associated with autistic and schizotypal traits influence low-level aspects of temporal binding across sensory modalities, including their malleability following alpha-band stimulation.

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10. Neufeld J, van Leeuwen TM, Kuja-Halkola R, Lundström S, Larsson H, Lichtenstein P, Bölte S, Mataix-Cols D, Taylor MJ. Genetic and environmental contributions to the link between synaesthesia and neurodevelopmental and psychiatric features: a twin study. Transl Psychiatry;2025 (Jul 12);15(1):240.

Synaesthesia is a sensory phenomenon where specific inputs such as written letters or tastes automatically trigger additional sensations (for instance colours). The phenomenon is more common in people on the autism spectrum compared to the general population and seems also to be associated with other neurodevelopmental and psychiatric conditions and features. We assessed the associations between self-reported synaesthesia and eight psychiatric / neurodevelopment features in 18-year-old twins and estimated the genetic and environmental contributions to these associations using classical twin modelling. All of the neurodevelopmental / psychiatric features (related to autism, ADHD, obsessive-compulsive disorder, anxiety, depression, psychotic-like experiences, eating disorders, and (hypo-)mania) correlated positively with self-reported synaesthesia. The strongest association was found with obsessive-compulsive features (r = 0.28). Genetic factors explained more than 50% of most these associations. Environmental factors that are not shared by twins (non-shared environment) influenced the associations to different degrees, while the influence of environmental factors that are shared by twins was estimated to be negligible. Rather than being specifically linked to autism, synaesthesia seems to be associated with a wider range of neurodevelopmental / psychiatric features, and especially obsessive-compulsive features. Genetic factors play a predominant role in most of these associations, suggesting that synaesthesia might share part of its genetic causes with several neurodevelopmental / psychiatric conditions.

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11. Park JC, Sim MA, Lee C, Park HE, Lee J, Choi SY, Byun S, Ko H, Lee H, Kim SW, Noh J, Park G, Lee S, Kim TK, Im SH. Gut microbiota and brain-resident CD4(+) T cells shape behavioral outcomes in autism spectrum disorder. Nat Commun;2025 (Jul 11);16(1):6422.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations in social, repetitive, and anxiety-like behaviors. While emerging evidence suggest a gut-brain etiology in ASD, the underlying mechanisms remain unclear. To dissect this axis, we developed a germ-free BTBR mouse model for ASD. The absence of gut microbiota in male mice ameliorates ASD-associated behaviors and reduces populations of inflammatory brain-resident T cells. Additionally, CD4(+) T cell depletion mitigates neuroinflammation and ASD behaviors, suggesting a gut-immune-brain axis. We identify several microbial and metabolic regulators of ASD, particularly those relevant to the glutamate/GABA ratio and 3-hydroxyglutaric acid. Using an in silico metabolite prediction model, we propose Limosilactobacillus reuteri IMB015 (IMB015) to be a probiotic candidate. Administration of IMB015 reduces the glutamate/GABA ratio and neuroinflammation, resulting in improved behaviors. Here we report a gut-immune-brain axis in which the gut microbiota and its metabolites can modulate brain-resident immune cells and ASD-associated behaviors.

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12. Shaban AM, Ameen O, Omar M, El Derbaly SA, Omara HR, Bayomi AI, Latif AAA, Elakabawy ZI, Khodir SA. Treadmill training protects valproic acid-induced autistic features via cerebellar AMPK/PPAR-γ dependent pathway and improves mitochondrial activity in mice. Sci Rep;2025 (Jul 12);15(1):25248.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired sociality and stereotypic behavior. Endurance training could modulate mitochondrial dysfunction sharing in the pathophysiology of ASD. We investigated the neuroprotective effects of training on VPA-induced ASD in mice. Forty mice were divided into control, Training, VPA, and VPA + Training groups. Mice were subjected to neurobehavioral tests. Assessment of the protein content of serum CRP, irisin, meteorin-like protein (metrnl), cerebellar inflammatory markers, serotonin, and BDNF was done by ELISA. MDA and catalase were also investigated using a colorimetric technique. Cerebellar citrate synthase (CS) enzyme activity was also measured. Cerebellar AMPK, PPAR-ɣ, and metrnl gene expressions were assessed via RT-PCR. Cerebellar immunohistochemical studies of GFAP, Bax, and PPAR-γ markers were conducted. Statistical methods were used in the data analysis, including one-way ANOVA, and t-tests. The VPA group showed significant impairments in social interaction, and cognition in neurobehavioral tests (P = 0.000). A significant increase of CRP, MDA, and inflammatory markers associated with a significant reduction in irisin, metrnl, catalase, CS, serotonin, and BDNF (P = 0.000) was noticed. Besides, cerebellar AMPK and PPAR-γ gene expressions were down-regulated. Significant cerebellar degenerative changes were also observed (P = 0.000). Training dramatically reversed VPA-induced neurobehavioral, biochemical, and cerebellar degenerative changes. Endurance training has anti-inflammatory, anti-apoptotic, and antioxidant properties. Adipo-myokines release, enhanced mitochondrial activity, and activation of AMPK and PPAR-γ pathways could be involved mechanisms. Training programs are a promising strategy for addressing the social and neurobehavioral impairments linked to ASD, according to the muscle-brain interplay.

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13. Valkanas H, McFadden K, Mignacca I, Qi X, Jordan M, Bayoumi I, Li P. Impact of the COVID-19 era on preventative primary care for children 0-5 years old: a scoping review. BMC Prim Care;2025 (Jul 11);26(1):221.

BACKGROUND: Restrictions to routine preventative primary care well child visits (WCV) during COVID-19 may have affected a variety of outcomes for young children including growth, development, and the identification and management of developmental delays. To better understand the effect of the pandemic on these outcomes, we conducted a scoping review of studies published between March 2020 and April 2024. The objectives of this scoping review were to determine the impact of the COVID-19 era on WCV attendance and developmental outcomes in children 0-5 years old. RESULTS: 23 articles met inclusion criteria. Most studies were conducted in the U.S. The overall COVID-19 era WCV rate was lower compared to pre-COVID visit rates. Higher rates of missed WCVs and reduced access were reported for racialized children and those from families with lower socioeconomic status. Studies measuring developmental outcomes found associations between children born during the pandemic and increased rates of expressive language delays, decreased personal-social skills, increased delays in achieving verbal, motor, and overall cognitive performance milestones, increased externalizing behaviours, and decreased prosocial behaviour. No study examined the impact of WCV attendance rates on developmental outcomes. CONCLUSIONS: During the COVID-19 pandemic, infants, toddlers, and young children attended fewer preventative primary care visits and pandemic-born children were more likely to show signs of developmental delay. This review highlights the need for further research to better understand the longitudinal impact of reduced access to preventative primary care and child health outcomes, including the early detection of, and referral for, developmental delays.

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14. Zarate-Lopez D, García-Carrillo R, Castro-Sánchez L, Galvez-Contreras AY, Gonzalez-Perez O. Spironolactone Partially Reverses Autism-Like Behaviors Linked to ErbB4 and mTOR Phosphorylation in the Mouse Prefrontal Cortex and Striatum. Arch Med Res;2025 (Jul 10);56(7):103254.

BACKGROUND AND AIMS: Autism spectrum disorder (ASD) is a condition resulting from a combination of genetic and environmental influences that lead to atypical brain development, particularly in regions such as the striatum and prefrontal cortex. There is increasing evidence linking the epidermal growth factor (EGF) and its receptor (EGFR or ErbB1) to the etiopathogenesis of ASD. However, ErbB4, another ErbB member, has also been implicated in this process. To investigate whether dysregulation of ErbB4 and its downstream mTOR signaling pathway in the striatum and prefrontal cortex contributes to stereotypical behaviors and social deficits in an autism-like rodent model. METHODS: We analyzed the phosphorylation levels of ErbB4and mTOR in the prefrontal cortex and striatum of 31 d old mice that were prenatally exposed to valproate (VPA; 500 mg/kg) or the control vehicle (0.9 % NaCl). Social and stereotypic behaviors were assessed using the three-chamber social test and the marble burying test, respectively. Then, the VPA groups were treated with 50 mg/kg of spironolactone, a selective ErbB4 antagonist. RESULTS: Prenatal exposure to VPA induced deficits in social interaction and an increase in repetitive behaviors. These behaviors coexist with dysregulation of the ErbB4 phosphorylation and modifications in the mTOR signaling pathway in both brain regions. Treatment with spironolactone reduced repetitive behaviors, which was consistent with reduced ErbB4 phosphorylation and mTOR signaling. CONCLUSIONS: These results support the idea that ErbB4 has abnormal expression and activity levels in the striatum and prefrontal cortex. Antagonizing ErbB4 with spironolactone improves repetitive behavioral patterns associated with ASD.

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15. Zhang Y, Zhao X, Gao C, Shi S, Chen M, Guo B, Hu S, Mei D, Duan X, Wang X. Deficiency of calretinin in prefrontal cortex causes behavioral deficits relevant to autism spectrum disorder in mice. Mol Brain;2025 (Jul 12);18(1):61.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms including deficits in social interaction, repetitive and stereotyped behaviors, along with higher levels of anxiety and cognitive impairments. Previous studies demonstrate pronounced reduced density of calretinin (CR)-expressing GABAergic interneurons in both ASD patients and animal models. The object of the current study was to determine the role of CR in ASD-relevant behavioral aberrations. Herein, the mRNA and protein levels of CR in the prefrontal cortex (PFC) of mouse model of ASD based on prenatal exposure to valproic acid (VPA) were determined by qRT-PCR and Western blot analysis, respectively. Moreover, the behavioral abnormalities in naive mice with CR deficiency mediated by recombinant adeno-associated virus (rAAV) were evaluated in a comprehensive testing battery including social interaction, marble burying, self-grooming, open-field, elevated plus maze and novel object recognition tests. Furthermore, the action potential changes caused by CR deficiency were examined in neurons within the PFC in naive mouse. The results show that the mRNA and protein levels of PFC CR of VPA-induced mouse ASD model were reduced. Concomitantly, mice with CR knockdown displayed ASD-like behavioral aberrations, such as social impairments, elevated stereotypes, anxiety and memory defects. Intriguingly, patch-clamp recordings revealed that CR knockdown provoked decreased neuronal excitability by increasing action potential discharge frequencies together with decreased action potential threshold and rheobase. Our findings support a notion that CR knockdown might contribute to ASD-like phenotypes, with the pathogenesis most likely stemming from increased neuronal excitability.

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