1. Ahmad B, Dumbuya JS, Tang JX, Li W, Chen X, Lu J. Rett syndrome: Pathogenicity and regulation of MECP2 (human) and Mecp2 (mouse) genes and their protein products through various molecular mechanisms. Mutat Res Rev Mutat Res;2025 (Jul 17);796:108553.

Rett syndrome was first described over 50 years ago as an unusual clinical entity. Mutations in the X-linked MECP2 gene are the primary causes of Rett syndrome. The unstructured MeCP2 protein adopts various functional conformations, complicating its study. Researchers have investigated the pathogenicity and regulation of MECP2 through mechanisms such as apoptosis, mitophagy, the PI3K/AKT/mTOR pathway, BMP signaling, NF-kB, STAT3, and the Wnt/β-catenin pathway. These mechanisms have not been reviewed in such detail before. Summarizing these pathways is essential for facilitating further exploration by researchers; therefore, we have comprehensively summarized these pathways.

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2. Ährlund-Richter S, Harpe J, Fernandes G, Lam R, Sur M. Persistent Disruptions in Prefrontal Connectivity Despite Behavioral Rescue by Environmental Enrichment in a Mouse Model of Rett Syndrome. J Comp Neurol;2025 (Jul);533(7):e70073.

Rett syndrome, a neurodevelopmental disorder caused by loss-of-function mutations in the MECP2 gene, is characterized by severe motor, cognitive, and emotional impairments. Some of the deficits may result from changes in cortical connections, especially downstream projections of the prefrontal cortex (PFC), which may also be targets of restoration following rearing conditions such as environmental enrichment that alleviate specific symptoms. Here, using a heterozygous Mecp2(+/-) female mouse model closely analogous to human Rett syndrome, we investigated the impact of early environmental enrichment on behavioral deficits and PFC connectivity. Behavioral analyses revealed that enriched housing rescued fine motor deficits and reduced anxiety, with enrichment-housed Mecp2(+/-) mice performing comparably to wild-type (WT) controls in rotarod and open field assays. Anatomical mapping of top-down anterior cingulate cortex (ACA) projections demonstrated altered PFC connectivity in Mecp2(+/-) mice, with increased axonal density in the somatosensory cortex and decreased density in the motor cortex compared to WT controls. ACA axons revealed shifts in hemispheric distribution, particularly in the medial network regions, with Mecp2(+/-) mice exhibiting reduced ipsilateral dominance. These changes were unaffected by enriched housing, suggesting that structural abnormalities in PFC connectivity persist despite behavioral improvements. Enriched housing rescued brain-derived neurotrophic factor (BDNF) levels in the hippocampus but failed to restore BDNF levels in the PFC, consistent with the persistent deficits observed in prefrontal axonal projections. These findings highlight the focal nature of changes induced by reduction of MeCP2 and by exposure to environmental enrichment and suggest that environmental enrichment starting in adolescence can alleviate behavioral deficits in Mecp2(+/-) mice without reversing abnormalities in large-scale cortical connectivity.

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3. Akter H, Rahman MM, Mim RA, Rahaman A, Eshaque TB, Hossain SA, Ganguly A, Omar FB, Taniya MA, Hasan N, Islam A, Jamalalail B, Nassir N, Zehra B, Sarker S, Uddin KMF, Nabi A, Woodbury-Smith M, Uddin M. Genomic insights into Rett syndrome-like features in Bangladeshi participants. Genet Med Open;2025;3:103438.

PURPOSE: Rett syndrome (RTT) is a neurological disorder marked by the loss of developmental milestones. Classic RTT involves variants in the methyl-CpG-binding protein 2 (MECP2) gene. Our study examines the genetic basis of typical and atypical RTT, along with RTT-like phenotypes, using MECP2-targeted sequencing (TS) and exome sequencing (ES). METHODS: MECP2 sequencing was conducted on 27 Bangladeshi female participants with RTT features. ES was subsequently conducted on the 13 participants who tested negative for MECP2 variants. Data were processed using the Genome Analysis Toolkit and American College of Medical Genetics and Genomics-guided pathogenicity analysis was conducted with ANNOVAR and GenomeArc Horizon. Copy-number variation analysis was performed using CNVkit, and variants were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: Of the 27 participants, 51.9% (14/27) had pathogenic MECP2 variants, all exhibiting the classic RTT phenotype, yielding an 87.5% (14/16) diagnostic rate for classic RTT through TS. The identified variants included 3 missense, 3 nonsense, and 3 frameshift deletions. Among the 13 MECP2-negative participants who underwent ES, 69.2% (9/13) harbored pathogenic variants, whereas 23.1% (3/13) carried a variant of uncertain significance, and 7.7% (1/13) had no clinically relevant variants. ES analysis identified 6 candidate genes were associated with atypical RTT (CACNA1E) and RTT-like phenotypes (ARHGEF9, KMT2C, TBC1D23, PGAP3, and LEO1). The overall diagnostic yield for TS and ES was 85.2% (23/27). CONCLUSION: This genetic study of clinically diagnosed Bangladeshi RTT participants identifies new genes involved in the etiology of RTT-like phenotypes and expands the phenotypic spectrum of known genes linked to neurodevelopmental disorders.

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4. Bar I, Eden S, Golan O. Is the Association Between Emotion Recognition and Social Functioning Mediated by Cognitive Empathy and Emotional Language? An Examination of School-Aged Autistic Children. Autism Res;2025 (Jul 17)

Children with autism spectrum disorder (ASD) face substantial challenges in understanding emotions, including difficulty in recognizing emotions through nonverbal cues, interpreting others’ affective and mental states, and developing emotional vocabulary. Research suggests that the association between emotion recognition and social functioning is mediated by emotional language and cognitive empathy. However, this relationship remains underexplored in autistic children. Addressing this gap was the primary goal of this study, which comprised 116 autistic children (17 females), aged 7-10 (M = 8.26, SD = 0.76). Participants completed a comprehensive assessment battery, comprising multi-modal emotion recognition, cognitive empathy, and emotional language tasks. Social functioning was evaluated through naturalistic observations during free play, supplemented by a parent-reported standardized measure. Path analysis results revealed that after controlling for age, cognitive abilities, and autism severity, the relationship between emotion recognition and social functioning was mediated by cognitive empathy. Additionally, emotional language emerged as a contributing factor, enhancing cognitive empathy and further supporting its role in social functioning. These findings present an indirect path between emotion recognition and social functioning through emotional language and cognitive empathy, highlighting the importance of targeting these components in interventions aimed at promoting social communication and adaptive social skills in autistic children.

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5. Defresne P. Considering autism diagnosis through the lens of social cognition can lead to mistakes. Neurosci Biobehav Rev;2025 (Jul 14):106286.

Although « social deficits » are a core feature of autism, this article highlights several conceptual and practical issues regarding the reliability and reproducibility of autism diagnoses based on social cognition evaluation. We argue that autism is not merely a social issue -at least not exclusively- nor is it a variable assemblage of independent social and non-social traits. Rather, it should be understood as a distinct way of organizing cognitive priorities, characterized by heightened attention to perceptual and mechanistic features, sometimes at the expense of semantic and socially oriented aspects. In autism, social signs are highly sensitive but not necessarily specific. For these reasons, we support Mottron’s proposal to redefine the concept of autism by recognizing a universal prototype based on the presence of positive and specific clinical signs.

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6. English MC, Poulsen RE, Maybery MT, McAlpine D, Sowman PF, Pellicano E. Psychometric evaluation of the Comprehensive Autistic Trait Inventory in autistic and non-autistic adults. Autism;2025 (Jul 16):13623613251347740.

Measures of autistic traits are only useful – for pre-diagnostic screening, exploring individual differences, and gaining personal insight – if they efficiently and accurately assess autism as currently conceptualised while maintaining psychometric validity across different demographic groups. We recruited 1322 autistic and 1279 non-autistic adults who varied in autism status (non-autistic, diagnosed autistic, self-identifying autistic) and gender (cisgender men, cisgender women, gender diverse) to assess the psychometric properties of the Comprehensive Autistic Trait Inventory, a recently developed measure of autistic traits that examines six trait domains using 42 self-report statements. Factor fit for the six subscales was appropriate, as was total-scale and subscale reliability. Importantly, measurement invariance was demonstrated based on both autism status and gender, indicating that Comprehensive Autistic Trait Inventory scores of these group members can be directly compared. Autistic traits were highly similar between diagnosed and self-identifying autistic adults, while gender-diverse participants showed more autistic traits than their cisgender counterparts. A total-scale discrimination threshold of 147.5 calculated was suggested which corresponded to sensitivity and specificity of 77.20 and 87.41, respectively. Our analysis indicates that the Comprehensive Autistic Trait Inventory is a practical measure of autistic traits in non-autistic and autistic participants that is useful for researchers and clinicians and for affirming self-identity.Lay abstractThe Comprehensive Autistic Trait Inventory (CATI) is a free questionnaire designed to measure autistic traits in both autistic and non-autistic adults. The CATI includes 42 items focusing on six areas: Social Interactions, Communication, Social Camouflage, Self-Regulating Behaviours, Cognitive Flexibility, and Sensory Sensitivity. Here, we set out to determine whether the CATI can accurately measure autistic traits in both autistic (both diagnosed and self-identifying) and non-autistic people, as well as people of different genders. We also wanted to explore the extent to which trait scores differed between these groups of individuals. Our study recruited over 2600 participants, including 1322 autistic and 1279 non-autistic adults. Our findings suggest that the CATI works the way it was designed to. It is a reliable and accurate tool for measuring autistic traits, can distinguish between autistic and non-autistic people, and appears appropriate for people of different genders. Notably, we found that people who self-identify as autistic have similar trait scores to those with a clinical diagnosis of autism and that gender-diverse people scored higher on autistic traits compared to cisgender people. Our data suggest that the CATI is a useful tool for measuring autistic traits in autistic and non-autistic people and for understanding the way that autistic people vary from one another. It should be helpful for researchers and clinicians, and support a public understanding of autism.

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7. G S, I NK. Effectiveness of Reflex Integration Approach on Asymmetric Tonic Neck Reflex in a Child With Developmental Delay-A Case Study. Physiother Res Int;2025 (Jul);30(3):e70086.

BACKGROUND: Developmental delays in children pose significant challenges, necessitating effective intervention strategies to promote optimal development. Reflex integration therapy, which involves structured movement exercises to encourage reflex maturation, has emerged as a promising approach to address developmental delays, yet its efficacy remains underexplored in clinical settings. AIM: This study aimed to evaluate the effectiveness of reflex integration therapy in a one-year-and-six-month-old female child diagnosed with developmental delay, focusing on integrating the asymmetric tonic neck reflex (ATNR) and enhancing gross motor function. CASE DESCRIPTION: The subject, Baby Dhanvi, presented with persistent ATNR and failure to achieve age-appropriate milestones despite her age. Treatment interventions included reflex integration therapy, exercises targeting motor skills, vestibular stimulation, and verbal and visual stimulation. The therapy sessions spanned a period of 20 days, with assessments conducted pre- and post-treatment. RESULTS: After 20 days of therapy, significant improvements were observed in ATNR integration, as measured by the Sally Goddard Reflex Rating Scale. Additionally, Baby Dhanvi exhibited moderate enhancement in gross motor function, leading to the attainment of previously unmet milestones, as evidenced by the Trivandrum Development Screening Chart. CONCLUSION: This case study provides compelling evidence supporting the efficacy of reflex integration therapy in addressing developmental delay, particularly in integrating ATNR and enhancing gross motor function. The findings underscore the potential of reflex integration approaches in clinical settings, emphasizing the importance of further research and application to optimize outcomes for children with developmental delays.

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8. Gadban A, Gunapala KM, Taylor V, Benvenisty N. Therapeutic strategies for fragile X syndrome and implications for other gene-silencing disorders. Nat Genet;2025 (Jul 17)

Gene-silencing disorders, of which fragile X syndrome (FXS) is the most prevalent, are diseases caused by a blockade of gene transcription, usually due to DNA hypermethylation. FXS is a common form of inherited intellectual disability and autism. Unlike most hereditary diseases driven by mutations within the protein-coding region of a gene, FXS is caused by a trinucleotide expansion in the 5′-untranslated region of the FMR1 gene, leading to hypermethylation and transcriptional silencing. Modeling FXS with human pluripotent stem cells offers a clinically relevant platform to study disease mechanisms and explore potential therapies through reactivating FMR1 expression by genetic and epigenetic means or through drug screening. This Perspective reviews the various cellular models and therapeutic strategies proposed over the past decade, highlighting their potential to advance the treatment of FXS. We also discuss the benefits and challenges of gene activation therapies, drawing comparisons with other gene-silencing disorders, including imprinting diseases and X-linked disorders.

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9. Hagerman RJ, Hagerman PJ. The Spectrum of Fragile X Disorders. N Engl J Med;2025 (Jul 17);393(3):281-288.

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10. Han GQ, Kat SC, Wang H, Yang YL, Ma ZH, Yin TN, Sun YJ, Tang XZ, Gong XY, Wang D, Li L, Sun BX, Zhao LY, Su X, Chen JL, Chen X, Wang HL, Li XY, Liu HL, Li X, Yan CG, Liu J. Alterations in whole-brain white matter fiber networks in individuals with autism spectrum disorder after social skills training. Brain Res Bull;2025 (Jul 14);229:111466.

Social skills training (SST) has demonstrated efficacy in improving social deficits in individuals with autism spectrum disorder (ASD), but the underlying neural mechanisms remain unclear. This study investigated alterations in whole-brain white matter network topology after SST in ASD individuals and explored potential correlation with improvements in social interaction deficits. 38 ASD patients aged 12 – 30 years were recruited, including 19 who completed magnetic resonance imaging (MRI) scans and social responsiveness scale (SRS) assessments at both baseline and the endpoint of a 14-week SST (training group) and 19 age-, sex-, and IQ-matched patients who underwent MRI scans and SRS assessment at the same time points but did not receive SST (control group). White matter connectivity matrices were constructed using diffusion tensor imaging (DTI), and graph theory analysis was used to assess global and nodal network properties. Paired t-tests and independent-samples t-tests were used for within- and between-group comparisons, respectively. Pearson’s partial correlation was used to examine associations between network changes and SRS scores changes. After SST, four edges showed significant changes in white matter connectivity (FDR-corrected), with three increased and one decreased in the training group. Changes in nodal betweenness were also observed. While SRS scores significantly decreased in the training group, no significant correlations were found between neuroimaging changes and behavioral improvements, possibly due to the limited sample size. These findings suggest that SST may reshape white matter network, offering insights into its neural mechanisms and informing novel ASD intervention strategies.

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11. Kim YK, Park PG. Impact of early life antibiotic exposure on the preschool developmental status: a nationwide population-based study. BMJ Paediatr Open;2025 (Jul 16);9(1)

OBJECTIVE: Growing concerns exist about the potential adverse effects of early antibiotic exposure on neurodevelopmental outcomes. However, large-scale studies exploring these implications in early childhood are rare. DESIGN: A nationwide, population-based retrospective cohort study using data from the Korean National Health Insurance System and the National Health Screening Program for Infants and Children (NHSPIC) between 2015 and 2022. PATIENTS: A total of 1 848 841 children who participated in the NHSPIC at both 4-6 months and 54-60 months of age were included. INTERVENTIONS: Antibiotic exposure under 90 days old. MAIN OUTCOME MEASURES: Developmental delays in preschool-aged children assessed by the Korean Developmental Screening Test at 54-60 month of age. RESULTS: Among the 1 848 841 children assessed, 23% experienced antibiotic exposure within the first 3 months of life. Early use of antibiotics was linked to a slightly elevated risk of developmental delays at a median age of 4.94 years (OR 1.03, 95% CI 1.00 to 1.17), particularly affecting gross motor (OR 1.08, 95% CI 1.04 to 1.13), fine motor (OR 1.09, 95% CI 1.05 to 1.13), cognition (OR 1.08, 95% CI 1.04 to 1.13) and communication (OR 1.08, 95% CI 1.04 to 1.12). A dose-response relationship was also observed, with longer durations of antibiotic exposure associated with an increased risk of developmental delays. CONCLUSIONS: Exposure to antibiotics in infants under 90 days old may be associated with a modest increase in the risk of global developmental delays, especially in motor skills, cognitive functions and communication abilities. Careful consideration is necessary when prescribing antibiotics to this age group.

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12. Leonova O, Baykov E, Krutko A. What Cervical MRI Findings Can Tell About ACDF Outcomes and Risks of ASD. Clin Spine Surg;2025 (Jul 17)

STUDY DESIGN: A retrospective analysis of data on patients with cervical degenerative disc disease who underwent single-level anterior cervical discectomy and fusion (ACDF). OBJECTIVE: To determine the association between preoperative cervical MRI parameters and surgical outcomes, and their role in the adjacent segment disease (ASD). SUMMARY OF BACKGROUND DATA: There is no evidence on what preoperative findings are related to ACDF outcomes, and the progression of postoperative degenerative changes at the adjacent levels has not been found yet. METHODS: The patients’ demographic data, cervical MRI findings at all cervical levels and clinical data were collected preoperatively and postoperatively. A comparative analysis of MRIs of the levels adjacent and nondjacent to ACDF was performed to find out whether or not they were undergoing accelerated degeneration. A regression analysis was carried out for the identification of predictors of fusion rates and implant subsidence. RESULTS: The study included 121 patients at visit 1 and 83 at visit 2. The median follow-up duration was 26.5 [18.9; 33.1] months. Complete fusions were observed in 85.5% of the patients (71/83), and implant subsidence was observed in 40% of the patients (33/83). Neither failed fusions nor implant subsidence were significant to clinical data (P>0.05). Significant changes in the Modic changes ratio of type 1 to type 2 were observed 1 or 2 segments above ACDF (P>0.05), along with an increase in the endplate damage there (P<0.001). Endplate defects grade are a strong and independent predictor of implant subsidence at the same level (OR=1.3-12.94, P<0.05). CONCLUSIONS: At the levels adjacent to and above the ACDF segment, there is a change in the Modic change type-to-type ratio and an increase in the endplate damage. However, these changes in MRI parameters cannot be regarded as evidence for accelerated segment degeneration due to ACDF. Endplate defects revealed on preoperative MRI scans are predictors of implant subsidence at the same level.

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13. Meng S, Huang W, Peng B, Zhao X, Feng Q, Liu W, Liu W, Wang L, Ge L, Lin R, Zeng S, Sheng T. Caries influences the composition of oral microorganisms in male children with ASD. Microb Pathog;2025 (Jul 14):107904.

BACKGROUND: Autism Spectrum Disorders (ASD) is a prevalent neurodevelopmental disorder, with growing evidence suggesting that certain oral microorganisms may worsen ASD symptoms. Caries is closely linked to the nervous system and influences the composition of oral microorganisms. Therefore, when studying the oral microbial composition in ASD, the effects of caries must be excluded to accurately identify potential oral causative agents of ASD. METHODS: A case-control study was conducted with 30 children diagnosed with ASD and 34 typically developing (TD) control children, both with and without caries, from Guangzhou city. Participants were categorized into four groups: ASD without caries (ASD-N), ASD with caries (ASD-C), TD without caries (TD-N), and TD with caries (TD-C). Plaque and saliva samples were collected from all participants and analyzed using 16S rRNA high-throughput sequencing to evaluate changes in oral microbial composition and diversity in children with ASD under varying caries conditions. RESULTS: The alpha diversity of plaque and saliva microorganisms was generally lower, and beta diversity differed significantly between children with ASD and control groups. At the phylum level, the two most dominant phyla were Bacillota and Actinomycetota. At the genus level, the predominant genera were Streptococcus and Porphyromonas. LEfSe analysis revealed that certain taxa, such as Ruminococcaceae bacterium UCG-005 and Lactobacillus mucilaginosus in dental plaque, and Actinobacillus in saliva, were significantly more abundant in caries-free ASD children compared to caries-free controls(P < 0.001). Furthermore, Prevotella, Carnobacterium and Suttonella in plaque, along with Peptostreptococcus in saliva, were more prevalent in caries-free ASD children compared to caries-affected controls (P < 0.001). CONCLUSION: Caries impacts the diversity and composition of oral microorganisms in children with ASD. The dominant genera, Streptococcus and Porphyromonas , are linked to both caries and the development of ASD. Certain biomarkers in children with caries were associated with caries, whereas others in caries-free ASD children were linked to ASD itself. These findings offer new insights into identifying the true oral pathogens related to ASD.

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14. Nance MG, Chang WR, Aldridge C, Burnsed J, Pelphrey K, Zanelli S, Puglia MH. From Breath to Brain: NICU Respiratory Interventions and Bedside Brain Signal Entropy Predict Later Autism Risk. medRxiv;2025 (Jul 8)

Premature infants often experience hypoxia and require prolonged ventilation, which can trigger systemic inflammation, damage the developing brain, and increase the risk of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Early intervention is key for ensuring optimal outcomes for those with ASD; thus emphasizing the critical importance of accurately identifying infants at risk as early as possible. Here, infants underwent electroencephalography during social (held) and nonsocial (not held) resting state conditions to assess brain signal variability, saliva collection to determine inflammation, calculation of a novel Prognostic Respiratory Intensity Scoring Metric (PRISM) to assess the burden of respiratory support, and ASD testing in toddlerhood. Higher PRISM scores were associated with increased brain signal entropy during the nonsocial resting state. However, this association was not observed in the social resting state condition – particularly for male babies. Interestingly in female infants, we saw that the relationship between brain signal entropy and PRISM scores were potentially mediated by cytokines. Notably, the interaction between nonsocial resting state brain signal entropy, sex, and PRISM scores predicted risk of developing ASD with 88% accuracy. These non-invasive measures can identify infants at the highest risk for an ASD diagnosis before discharge.

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15. Panjabud P, Kanlayaprasit S, Thongkorn S, Songsritaya K, Lertpeerapan P, Kasitipradit K, Jantheang T, Sarobol S, Saeliw T, Hu VW, Imai T, Sarachana T. Prenatal exposure to bisphenol A disrupts RNA splicing in the prefrontal cortex and promotes behaviors related to autism in offspring. Sci Rep;2025 (Jul 17);15(1):25996.

Prenatal exposure to bisphenol A (BPA), a common endocrine disruptor, has been increasingly implicated in neurodevelopmental disorders, including autism spectrum disorder. This study explores the molecular mechanisms by which prenatal BPA exposure affects alternative RNA splicing in the prefrontal cortex and investigates the potential link between alternative RNA splicing and autism-related behaviors in rat offspring. Using RNA sequencing and high-resolution melting real-time PCR, we identified differentially alternative splicing events associated with autism candidate genes. Gene ontology and pathway analyses revealed significant enrichment of differentially alternative splicing genes and neurological pathways relevant to autism. BPA appears to act through autism-related transcription factors, affecting RNA-binding proteins. Altered expressions of these RNA-binding proteins influenced alternative RNA splicing events within key autism-related genes, implicating them in disrupted synaptogenesis. Behavioral analyses of offspring exposed to BPA revealed autism-associated traits, including hyperactivity, anxiety, and aggression, which correlated with the observed sex-specific alternative RNA splicing patterns. These findings suggest that BPA-induced alterations of transcription factors and RNA-binding proteins affect alternative RNA splicing and synaptic development, potentially contributing to autism pathophysiology. This research underscores the role of environmental factors in autism etiology and highlights the importance of awareness and preventive measures against prenatal BPA exposure.

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16. Perzolli S, Bertamini G, Venuti P, Bentenuto A. Parental stress, mental health, and child traits in Italian mothers and fathers of autistic children. Front Psychol;2025;16:1593255.

INTRODUCTION: Several studies have investigated differences between mothers’ and fathers’ stress and mental health in the context of autistic children parenting. However, fewer have examined differences in parent-reported perceptions of their children’s behaviors, symptom severity, and their associations with parental variables. This study aimed to compare parental stress (Parental Stress Index-Short From), mental health (Symptom Checklist-90), and parent-reported perceptions of child behaviors (Child Behavior Checklist-CBCL) and symptom severity (Social Responsiveness Scale-SRS). In Italian mothers and fathers of autistic children while exploring how parental wellbeing relates to both parent-reported and clinically assessed child characteristics. METHODS: A total of 102 parents (51 mothers and 51 fathers) of autistic children aged 4-19 years completed questionnaires assessing stress, mental health, children’s behavioral traits and symptom severity. Standardized clinical tests directly measured children’s cognitive functioning (IQ) and symptom severity. Group differences between mothers and fathers were analyzed using inferential tests, while Linear Mixed Models were employed to examine the effect of parent, parental stress and mental health on parent-reported perceptions of children’s behaviors and symptom severity, as well as clinically measured children’s cognitive functioning and symptoms severity. RESULTS: Mothers and fathers reported similar stress levels but mothers showed higher levels of mental health symptoms and perceived their children as having more severe internalizing and externalizing behaviors and more severe symptomatology compared to fathers. Parental mental health was significantly associated with parent-reported child internalizing behaviors, while parental stress was linked to externalizing behaviors and parent-reported autism severity. No effects emerged for child cognitive functioning, and the model on clinician-rated autism severity failed to converge. DISCUSSION: These findings emphasize the interconnected nature of parental wellbeing, parent-reported child characteristics, and clinically assessed child traits. Recognizing these links may inform more effective, targeted support strategies for families raising autistic children.

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17. Ren Y, Mlodnicka A, Calub CA, Hertz-Picciotto I, Schweitzer JB. Predicting later ADHD presentation types from early childhood autism and intellectual disability. Eur Child Adolesc Psychiatry;2025 (Jul 17)

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) and autism are both neurodevelopmental disorders associated with functional impairment in social, academic, and occupational domains. METHODS: This longitudinal study, a follow-up to the CHARGE Study (ReCHARGE), evaluated diagnosis of ADHD and its presentation type (Inattentive, Combined-Hyperactive/Impulsive), in a cohort of 8 to 20 year-olds from four developmental categories recruited at ages 2-5 years: Autism, developmental delay without autism (DD), other early concerns (OEC) or typical development (TD, controls from the general population) (n = 645). ADHD diagnosis was based on parent clinical interviews (DISC or MINI), observational methods and multiple rating scales. Multivariate Poisson log regression models were fit to estimate associations of early childhood neurodevelopment with later ADHD diagnoses. Adjusted confounding variables included child’s age, sex, parental ADHD, socioeconomic indicators, and maternal prenatal conditions. RESULTS: Of 645 participants, 213 (33.0%) met criteria for ADHD. Early childhood diagnosis was the strongest predictor. For Hyperactive/Impulsive or Combined presentation, relative risks (RRs [95% CI]) were 5.4 [3.0, 9.4] for autism, 4.4 [2.3, 8.4] for DD, and 3.1 [1.5, 6.1] for OEC. For Inattentive presentation, RRs were 2.6 [1.6, 4.2] for autism, 1.4 [0.7, 2.9] for DD, and 2.6 [1.4, 4.2] for OEC. For any ADHD presentation, RRs were 3.1 [2.2, 4.4] for autism, 2.4 [1.6, 3.6] for DD, and 2.4 [1.6, 3.6] for OEC. CONCLUSIONS: This study reinforces the need for evaluation of ADHD and its presentation type in autistic children and other developmental delays, as these youth are at high risk for ADHD. Clinicians should assess the presence of ADHD-related challenges across development and service needs in individuals with autism and/or DD due to their high ADHD risk.

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18. Serrano-Tomás MI, Contreras-Romero P, Parellada M, Chaves-Cordero J, Zamora J, Hengst M, Pozo P, Del Campo R, Guzmán-Salas S. Recognition of the microbial metabolite p-cresol in autism spectrum disorder: systematic review and meta-analysis. Front Mol Neurosci;2025;18:1576388.

INTRODUCTION: In recent years, research has focused on the gut-brain axis and its microbial metabolites as potential etiological or physiopathological agents of autism spectrum disorders (ASDs). Elevated levels of the organic compound para-cresol (p-cresol) have been reported in various populations of children with ASD, suggesting that it could be validated as a possible ASD biomarker related to microbiota. The aim of this study was to perform a systematic review of p-cresol in ASD along with a meta-analysis to elucidate the scientific evidence of its potential as a biomarker. METHODS: A search was performed in the PubMed, Web of Science and Scopus databases in May 2024. The Axis critical appraisal tool was used to evaluate the methodological quality of the studies included in the review. Three independent reviewers examined the identified records and performed data extraction. RESULTS: The systematic review yielded 15 articles, of which only 6 were ultimately used for the meta-analysis. Urinary p-cresol levels were significantly higher in those with ASD than in healthy controls, whereas no significant differences were observed in feces. CONCLUSION: This meta-analysis validates that in ASD an increased level of p-cresol is detected in urine, which could represent a marker of microbiota evolution assessment in the pathogenesis of the disease. However, further research is needed to determine whether there is a causal relationship between the role of this metabolite and the pathophysiology of ASD and to validate its clinical utility.

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19. Song W, Zuo B, Jiang C, Zhang Z. Brain Activity Within Prefrontal Cortex: A Resting-State fNIRS Comparative Study in High-Functioning Autism Preschoolers and Typically Developed Peers. J Biophotonics;2025 (Jul 16):e202500527.

We applied functional near-infrared spectroscopy (fNIRS) technology to detect brain function within the prefrontal cortex in 23 typically developing (TD) preschool children and 48 children with high-functioning autism (HFA), aiming to observe the differences in brain function within the prefrontal cortex between the two groups. We found that the activation degree of channels 6-7-11 corresponding to the activation area of the right prefrontal lobe in the HFA group, is significantly higher than that in the Typical Development TD group. Moreover, the number and intensity of brain functional connectivity in the HFA group are significantly lower than those in the TD group. The active areas of the brain network in the HFA group are not as concentrated as those in the TD group. This demonstrates that fNIRS detection can serve as a potential biomarker for brain activity within the prefrontal cortex of preschool children with HFA.

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20. Stump SM, Bohlen JF, Phan B, Maher BJ. Characterization of astrocyte density in the Pitt-Hopkins Syndrome mouse model of ASD. bioRxiv;2025 (Jul 12)

Transcription factor 4 (TCF4) is a proneural basic helix-loop-helix transcription factor that plays a critical role in brain development and is associated with a variety of psychiatric disorders including autism spectrum disorder (ASD), major depressive disorder, and schizophrenia. Autosomal dominant mutations in TCF4 result in a profound neurodevelopmental disorder called Pitt-Hopkins Syndrome (PTHS). Germline TCF4 loss-of-function (LOF) studies using human and mouse models have identified dysregulation in neural cell proliferation, genesis, and specification which lead to disruption in neuronal, astroglial and oligodendroglial lineages. In this study, we focused on the role of TCF4 in the genesis of the astrocyte lineage, specifically in the context of modeling PTHS. We show that germline heterozygous mutations in Tcf4 had no effect on the expression of astrocyte marker genes in primary astrocyte cultures and whole brain lysates. Immunohistochemical (IHC) analysis of pan- and subclass-specific astrocyte markers showed Tcf4 mutation had no effect on the proportions of astrocytes in the dorsal cortex and corpus callosum. Lastly, we tracked ventrally-derived astrocytes using an Nkx2.1 reporter mouse and observed that germline Tcf4 LOF did not result in misallocation of ventrally-derived astrocytes into the dorsal cortex, a phenotype previously observed when both Tcf4 alleles were conditionally deleted in the Nkx2.1 lineage. These data indicate that germline heterozygous TCF4 LOF, which models PTHS, does not appear to affect the astrocyte lineage at the cell population level.

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21. Turnage DM, Conner NE. Profound Autism Prevalence and Impact on Parental Caregiver Quality of Life. J Psychosoc Nurs Ment Health Serv;2025 (Jul 17):1-7.

PURPOSE: The current study aimed to examine the effects of profound autism on caregiver quality of life (QOL). METHOD: This cross-sectional study involved parental caregivers of children aged 3 to 21 years with autism spectrum disorder living in Florida. Data were collected through surveys assessing caregiver QOL across physical, psychological, and environmental domains. Linear regression analyses examined the relationship between profound autism and caregiver QOL. RESULTS: The prevalence of profound autism in the sample was 22.4%. Regression analyses revealed that profound autism significantly predicted lower QOL in physical (F = 5.07, p = 0.007), psychological (F = 5.92, p = 0.003), and environmental (F = 11.01, p < 0.001) domains. Parental caregivers of children with profound autism reported substantially decreased QOL compared to those with children at other levels of autism severity. CONCLUSION: Findings indicate that profound autism is a prevalent condition and significant risk factor for reduced caregiver QOL across multiple domains. The negative impacts on physical, psychological, and environmental well-being highlight the need for targeted support services for families with children who have profound autism. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].

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22. Zhong HJ, Pan ZY, Wei YF, Yu Q, Wu L, Wei H, He XX. Tongue-coating microbiota as a predictive biomarker of washed microbiota transplantation efficacy in pediatric autism: integration with clinical features. J Transl Med;2025 (Jul 16);23(1):799.

BACKGROUND: Alterations in both oral and gut microbiota have been identified in children with autism spectrum disorder (ASD), but the interaction between these microbiota and their potential to predict outcomes of fecal microbiota transplantation (FMT) remain poorly understood. METHODS: This study investigated the structure and function of the tongue-coating microbiota in children with ASD and explored its correlation with ASD symptoms and gut microbiota. Germ-free ASD mice, colonized with healthy gut microbiota, and children with ASD treated with washed microbiota transplantation (WMT) were assessed for changes in autism symptoms and microbiota composition. Predictive models were also developed based on pre-treatment tongue-coating microbiota and clinical features to forecast WMT outcomes. RESULTS: Significant alterations were detected in the tongue-coating microbiota of children with ASD, with several bacterial species showing associations with ASD symptoms and gut microbiota composition. Following WMT, both mice and children exhibited substantial improvements in autism-related behaviors, alongside marked shifts in their gut and tongue-coating microbiota. A significant decrease in Haemophilus in the tongue-coating microbiota, which positively correlated with ASD severity, was observed. Additionally, a reduction in chemoheterotrophic and fermentation functions in the tongue-coating microbiota was identified. Predictive models utilizing pre-treatment tongue-coating microbiota and clinical data demonstrated comparable accuracy to those based on gut microbiota for forecasting WMT outcomes. CONCLUSIONS: These findings highlight a significant interaction between gut and tongue-coating microbiota in ASD, which may play a pivotal role in treatment outcomes. Predictive models integrating pre-treatment microbiota and clinical features could improve precision treatment strategies for children with ASD undergoing WMT.

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