1. Amraoui N, Dali-Sahi M, Salmi T, Kachekouche Y, Harek Y, Benguella-Benmansour M, Berrahoui S, Dib J, Benosman C, Dennouni-Medjati N. GPx1 rs1050450 Polymorphism Modulates Selenium Status and Glutathione Peroxidase 1 Activity in Children with Autism Spectrum Disorder: A Case-Control Study from Western Algeria. Biol Trace Elem Res. 2025.

Oxidative stress plays a central role in autism spectrum disorder (ASD). The rs1050450 (Pro198Leu) polymorphism of glutathione peroxidase 1 (GPx1), a selenium-dependent antioxidant enzyme, may modulate selenium status and enzymatic activity. This case-control study included 75 children in western Algeria (35 children with ASD, 40 controls). Plasma selenium was quantified by voltammetry, erythrocyte GPx1 activity by spectrophotometry, and rs1050450 genotyping by PCR-RFLP. Children with ASD exhibited significantly lower plasma selenium (49.13 ± 10.75 vs. 68.84 ± 9.48 µg/L; p < 0.001) and reduced GPx1 activity (86.73 ± 36.08 vs. 116.71 ± 35.83 U/g Hb; p < 0.05). Remarkably, the TT genotype was found exclusively in ASD children (40.0%; 14/35) with complete absence in controls (0/40), yielding χ(2) = 18.01 (p < 0.001). The T allele was more frequent in ASD (47.1% vs. 22.5%; p = 0.003, Fisher p = 0.002). The TT genotype correlated with the lowest GPx1 activity. Selenium-GPx1 correlations varied dramatically by genotype: negative in ASD with CC (r = - 0.555; p < 0.001) and CT (r = - 0.450; p < 0.05), positive in controls with CT (r = 0.852; p < 0.001). Parental consanguinity was more frequent in ASD (28.6% vs. 10.0%; OR = 3.60; p = 0.072). This North African cohort demonstrates hyposelenemia, reduced GPx1 activity, and exclusive TT genotype presence in ASD, suggesting converging genetic-biochemical disruptions of selenium-dependent redox homeostasis. These findings warrant validation in larger cohorts for personalized nutritional interventions.

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2. Babu A, Orge FH. Risk of Ocular Pathology in Rett Syndrome. J Pediatr Ophthalmol Strabismus. 2025: 1-5.

PURPOSE: To assess the risk of developing ocular alignment disorders, refractive errors, amblyopia, and nystagmus in patients with Rett syndrome. METHODS: This retrospective cohort study used de-identified patient data from the TriNetX US Collaborative network and compared a Rett syndrome and a control cohort. Propensity score matching was conducted to balance demographics and well-characterized comorbidities. Statistical analysis calculated risk ratios (RRs) and 95% confidence intervals (CIs), with significance defined by excluding CIs between 0.9 and 1.1. RESULTS: Patients with Rett syndrome had an increased risk of developing strabismus (RR: 3.39; CI: 2.47 to 4.65) and risk for the specific horizontal subtypes of esotropia (RR: 4.06; CI: 2.26 to 7.26) and exotropia (RR: 2.92; CI: 1.83 ro 4.68). Additionally, patients with Rett syndrome had an increased risk of developing amblyopia (RR: 1.90; CI: 1.28 to 2.82) and nystagmus (RR: 1.98; CI: 1.12 to 3.53). No differences in risk were found for astigmatism, myopia, and hyperopia development given Rett syndrome diagnosis. CONCLUSIONS: These findings demonstrate the importance of regularly monitoring ocular health in patients with Rett syndrome and a need for further investigation into the underlying mechanisms linking the disease with these specific ocular pathologies.

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3. Batterjee M. Association between breastfeeding and autism spectrum condition in Saudi Arabia: a case-control study. Int Breastfeed J. 2025; 20(1): 79.

BACKGROUND: Autism spectrum condition (ASC) is a neurodevelopmental disorder characterized by persistent difficulties in social communication and repetitive behaviors. Emerging evidence suggests that early nutrition, particularly reduced breastfeeding exposure, may be associated with an increased risk of ASC. However, this evidence is limited, especially in non-Western populations. METHODS: We conducted an unmatched case-control study in Saudi Arabia to investigate the association between breastfeeding practices and ASC. Data were collected through an online questionnaire from mothers of children with and without ASC. Cases were children with a confirmed ASC diagnosis, and controls were neurotypical children without a diagnosis of ASC. Breastfeeding exposure was categorized according to the World Health Organization definitions (from highest to lowest exposure) as follows: exclusive, predominant, partial, or no breastfeeding. Logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Between 1 October 2024 and 25 January 2025, a total of 283 participants (126 cases and 157 controls) were recruited. A dose-response relationship was observed, where decreased breastfeeding exposure was associated with progressively higher odds of ASC (OR for trend: 1.58; 95% CI 1.24, 2.01). In univariable analyses, using exclusive breastfeeding as the reference category, partial breastfeeding was associated with increased odds of ASC (OR: 2.49; 95% CI 1.40, 4.42). Similarly, children who were not breastfed had significantly higher chance of ASC than the reference category (OR: 3.46; 95% CI 1.47, 8.13). The strength of these associations was attenuated after multivariable adjustment but remained statistically significant (OR: 2.28; 95% CI 1.22, 4.25 for partial versus exclusive breastfeeding and OR: 2.86; 95% CI 1.12, 7.26 for no breastfeeding versus exclusive breastfeeding). CONCLUSIONS: Our findings suggest that reduced breastfeeding exposure is associated with increased odds of ASC. However, these results should be interpreted cautiously, considering the inherent limitation of case-control studies and the potential of reverse causality.

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4. Benevides TW, Pham HH, Andresen ML, Bahr MR, Corey T, Nicholson J, Faughnan K, Jaremski JE, Langer C, Siasoco V, Hernandez-Hons A, Shore SM. Engagement to Identify Health Priorities of People With Intellectual and/or Developmental Disability. OTJR (Thorofare N J). 2025: 15394492251385448.

People with lived experiences are often excluded from development of solutions and decision-making related to health research and policy. To describe and demonstrate how high-quality engagement supports partner and project outcomes. The ultimate project outcome was to identify health priorities desired by people with intellectual and/or developmental disability (IDD) and the people who support achieving those priorities, including caregivers, clinicians, and payers/regulators. This capacity-building project implemented and evaluated methods of engagement of IDD self-advocates, caregivers/partners, clinicians, payers/regulators, and researchers. Our reliance on a variety of engagement approaches, but particularly graphic illustration and other visual engagement, yielded productive conversations to advance areas of priority. Partners felt satisfied with engagement and continued to participate at multiple points throughout the 2-year project. We identified nine illustrated priority health outcomes useful for research, practice, and policy change. Our engagement and priority-setting approach resulted in findings that partners found compelling personally and professionally. Identifying Health Priorities for People with Intellectual and Developmental Disabilities Through EngagementWhy is this an important issue? People with intellectual and/or developmental disabilities (IDDs) don’t always get good health care.What was the purpose of the project? This project had a big goal: to find out what health outcomes are most important to people with IDD. We first needed to create ways for many different partners to work together and share ideas.What did the project team do? We worked with different people, including adults with IDD, caregivers, clinicians, and those in charge of health insurance plans. Together, our team developed ways of working together. We used videos, drawings, and easy-to-understand language. We made sure everyone, including those with different communication needs, could take part. In total, 58 people shared their ideas about important health goals in meetings and online sessions.What were the results of this project? We learned that using drawings and other ways of showing ideas visually without words was helpful for many different groups of people. For people with IDD, having 1-on-1 meetings to prepare for larger group meetings was helpful. Videos sent before meetings to describe the agenda and discussion questions were helpful for both people with IDD and caregivers. We learned that people with IDD and other partners want research to address nine health priorities that affect positive outcomes of people with IDD.What do these findings add to what we know? We learned that using artist-created drawings and using other visual tools like Miro(®) were helpful for all people to work together.What are the potential weaknesses? We need to talk with more people about these health outcome priorities to be sure they are complete.How will these findings help people now or in the future? These ideas for helping many different partners work together are useful for other teams. The project outcome with illustrated priorities can help make these ideas more accessible to a wider audience. eng.

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5. Brook A. How the ASCENT model can help optimize exposure therapies for Autistic clients. Front Psychiatry. 2025; 16: 1569882.

Exposure therapies are very effective for alleviating anxiety, yet limited research has focused on optimizing their effectiveness for Autistic clients. This « Perspective » article describes how the ASCENT model can guide tailoring exposure therapies to be more effective and affirming for Autistic clients. This model proposes supporting clients in Autonomous and Affirming goal setting (A), adapting for differences in Sensory processing, Stimming, Structure, Special interests (S), Communication (C), and Executive functioning (E), practicing with Neurohumility (N), and being Trauma informed (T). Because the ASCENT model is based on traits of Autistic clients and effective ways of working with them, it can help guide tailoring a wide variety of anxiety treatments. This article provides examples of how the ASCENT model can be applied to increase the effectiveness of several different types of exposure therapies, as well as articulating when exposure is not appropriate and accommodation is necessary instead.

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6. Cai Y, Holmes J, Michelini G, Eley TC, Gathercole SE. Neurodevelopmental and Psychosocial Outcomes in Adolescence of Children with Early Diagnoses of ADHD, Autism, Dyscalculia and Dyslexia. Res Child Adolesc Psychopathol. 2025.

The study examined neurodevelopmental and psychosocial outcomes in adolescents aged 12 and 16 with childhood diagnoses of ADHD, autism, dyscalculia, or dyslexia. Participants were drawn from the Twins Early Development Study based on parent-reported diagnoses between ages 7 and 9 of ADHD (n = 54), autism (n = 50), dyscalculia (n = 282), and dyslexia (n = 695). A comparison group included 6,882 participants without neurodevelopmental diagnoses. Differences in ADHD and autistic traits, academic challenges, peer difficulties, and internalizing issues were explored between the comparison group and each neurodivergent group at ages 12 and 16. Across timepoints, neurodivergent groups showed distinct patterns of difficulties across domains relative to the comparison group. The ADHD group had higher levels of inattention and hyperactivity/impulsivity at 12 and 16, lower academic performance at 16, and elevated mental health challenges at 12. The autism group showed higher degrees of inattention, hyperactivity/impulsivity, autistic traits, and peer difficulties at 12 and 16. The dyscalculia group had challenges in all domains except for peer relationships at 12, with only mathematical underachievement persisting to 16. The dyslexia group showed difficulties in all domains at 12 with issues related to inattention, hyperactivity/impulsivity, academic achievement, and peer relationship persisting to 16. Whereas at age 12 the neurodivergent groups showed diagnosis-specific difficulties and broader neurodevelopmental and psychosocial challenges, by age 16 they were characterized by distinctive trajectories with persisting and resolved difficulties. These findings underscore the need for repeated, broad-based assessments to understand the changing needs of children with early neurodevelopmental diagnoses.

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7. Doulou F, Piolino P, Angeard N. Virtual reality programs targeting executive functions and social cognition evaluation and/or rehabilitation in children with ADHD or ASD-A narrative review. Front Psychol. 2025; 16: 1583052.

Various studies have underlined the possible effectiveness of innovative techniques, such as virtual reality (VR), during the assessment or the rehabilitation of cognition in clinical pediatric populations. This study aims to (a) review the VR environments designed to assess and/or enhance executive functions (EFs) and theory of mind (ToM) domains in children and adolescents with neurodevelopmental disorders and (b) evaluate the sensitivity and the efficacy of these VR tools. Following an overview of these studies (e.g., purpose and results), our study has two further goals: (1) to provide the methodological dimensions of each study (target skills/processes and clinical populations), and (2) to highlight the VR characteristics (e.g., sense of presence and immersive experience, the user’s point of view) implemented in the selected articles. A total of 75 studies published between 1996 and 2022 and fulfilling the selected criteria were found on database platforms such as PubMed or Science Direct. Our review demonstrates that VR could be useful as an assessment and training tool for cognitive and social impairments in pediatric clinical populations. However, the numerous clinical and VR designs highlight the need to develop a more systematic evaluation of VR programs to define what really works, especially in terms of generalization to more naturalistic settings.

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8. Duerden EG, Neufeld J, Crafa D. Social perception and cognition in autism. Sci Rep. 2025; 15(1): 38660.

Autism is a neurodevelopmental condition characterized by social communication differences and repetitive behaviors. Recently, autism research has shifted to reflect the need for individualized, ecologically valid models of social cognition difficulties. This Special Issue brings together innovative studies exploring how autistic individuals perceive and respond to social interactions, using a broad range of methodological approaches including psychophysical experiments, neuroimaging and behavioral measures. Emerging themes include differential processing in individuals on the spectrum in social cognition, social perception, eye contact, emotion regulation/arousal, and interpersonal synchrony. The collection also introduces novel translational approaches, such as using motion synchrony during diagnostic interviews and characterizing individual motor-sensory profiles. Together, the articles in the Special Issue reflect a paradigm shift in autism research from the previous more static views of social difficulties and moving toward a nuanced understanding of heterogeneity, compensation and adaptive potential. This body of work underscores the value of precision approaches to improve social cognition and lays the foundation for inclusive, strengths-based interventions.

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9. Dwivedi S, Rajput P, Akhtar A, Goli SH, Dusane A. Preclinical models for autism spectrum disorder: past, present, and future. Neuroscience. 2025; 591: 186-204.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders linked to neurobehavioral abnormalities in children. Despite substantial research suggesting the role of environmental and genetic variables in ASD development, the etiology and pathophysiology of autism still need exploration. To unveil the pathophysiology, genetics, and therapeutics of autism, many preclinical animal models are employed, with rodent models being most trusted. In the last two decades’ various non-rodent animal models and in vitro models for autism have been proposed, which are quick, economic, and trustworthy to investigate. However, there are concerns about mimicking behavioral and molecular features of autism. In this review, we have compiled the preclinical models that can help us comprehend the phenotypic and molecular characteristics of autism. The review discusses the reliability of available models along with their advantages and disadvantages. The inference from the review will provide insight to the researchers into all possible preclinical models for autism and select the best one to improve the translational value in ASD research.

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10. Fabio RA, Semino M, Perina M. Enhancing cognitive-motor recovery in Rett syndrome: effects of integrated intervention on neuropsychological and motor outcome. Front Psychol. 2025; 16: 1679593.

Cognitive-motor integration plays a crucial role in the rehabilitation of individuals with complex disabilities, where dissociated impairments in cognition and movement often hinder global functioning. In this study, we investigated the efficacy of an integrated neurorehabilitation program targeting both neuropsychological and motor domains in patients with Rett Syndrome. Baseline assessments included measures of attention, memory, and temporal sequencing, as well as gross, fine, and graphomotor abilities, evaluated using relevant GAIRS subscales (Global Assessment and Intervention Rating Scale). Nineteen patients were enrolled in an experimental group receiving specialized cognitive-motor training three times a week for two consecutive 5-week periods. A control group of 15 patients participated in standard educational activities without specific cognitive-motor intervention. Performance was evaluated at three time points: T0 (baseline), T1 (after 5 weeks), and T2 (after an additional 5 weeks). Results indicated significant improvements in both neuropsychological and motor functions in the experimental group, with gains observed at both T1 and T2. Notably, a strong and significant correlation emerged between improvements in motor and cognitive measures, underscoring the interdependence of these domains in neurodevelopmental conditions such as Rett Syndrome. These findings support the implementation of integrated cognitive-motor protocols in neurorehabilitation and highlight the value of synchronized interventions to foster global functioning in individuals with complex neurodevelopmental profiles.

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11. Fereshetyan K, Danielyan M, Yenkoyan K. Stage-Dependent Disruptions in Neurogenesis and Neurotrophins’ Production Following Prenatal and Postnatal Valproic Acid Exposure: Implications for Autism Spectrum Disorders. Cell Mol Neurobiol. 2025; 45(1): 95.

Autism spectrum disorders (ASD) are neurodevelopmental conditions involving impaired neuronal processes such as connectivity, synaptogenesis, and migration. Prenatal exposure to valproic acid (VPA), an anticonvulsant and mood stabilizer, is linked to increased ASD risk, with timing as a key factor. However, the molecular mechanisms of VPA-induced neurodevelopmental disruptions remain unclear. Building on our previous study, which characterized VPA-induced prenatal and postnatal ASD models with impaired social behavior, repetitive patterns, and altered brain connectivity, this study examines molecular changes in neurogenic brain regions. We analyzed the prefrontal cortex, hippocampus, and subventricular zone at key developmental time points (postnatal days 14 and 21), assessing neurotrophins (BDNF, Nt-3, IGF-β, GDNF) and markers of cell migration (DCX), differentiation (NeuN, GFAP), and synaptogenesis (synaptophysin). Our findings show that both prenatal and postnatal VPA exposure disrupt neurogenesis, with prenatal effects being more severe and persistent. Prenatal VPA significantly reduced BDNF in the subventricular zone and DCX in the olfactory bulb, suggesting impaired migration, while morphological analysis revealed thickening of ventricular lateral wall and disrupted cellular organization. Postnatal exposure led to transient neurotrophin changes, including delayed IGF-β production and an abnormal rise of BDNF levels. Elevated GFAP and reduced NeuN or synaptophysin in the prefrontal cortex, alongside increased neuronal markers in the hippocampus, suggest region-specific neuroglial imbalances. These findings highlight the stage-dependent vulnerability of the developing brain to VPA exposure, revealing distinct mechanisms of disruption in prenatal and postnatal administration. They underscore the need to minimize exposure risks during late gestation and early postnatal periods, which are crucial for neurodevelopment.

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12. Gordon M, Aounallah A, Russell A. Lighting the way: the LANTERN system for children’s autism referrals to enhance triage effectiveness and navigate frontline timely support. BMJ Paediatr Open. 2025; 9(1).

OBJECTIVES: To evaluate the implementation and outcomes of the Layered Assessment of Neurodevelopmental Needs, Evaluation of Referrals and Navigation of support (LANTERN) triage system developed to improve referral quality, reduce unnecessary delays and enhance support for children referred for autism diagnostic assessment. DESIGN: Service improvement informed by action-based methodology and clinical audit, employing descriptive analysis of administrative and outcome data. SETTING: A UK National Health Service community paediatric service covering 59 000 children aged 4-16. PARTICIPANTS: All referrals to the neurodevelopmental pathway for autism assessment from April 2019 to March 2025. INTERVENTION: The LANTERN system incorporates senior diagnostician-led triage, expanded evidence review and detailed guidance for families and referrers. MAIN OUTCOME MEASURES: Referral volume and acceptance rates, rates per 1000 population, patient experience via friends and family test and cost-effectiveness. RESULTS: Referral rates fell 25% over 5 years, and acceptance rates dropped from 79.6% (2019-2020) to 61% (2024-2025), compared with 92% in the wider region. LANTERN achieved a local referral rate of 4 per 1000 versus 33 system-wide. ‘Good’ or ‘very good’ family satisfaction rose from 35% to 95%. The system incurred an annual cost of £58 695 but avoided £96 025 in assessments not indicated, yielding a net saving of ~£37 330. CONCLUSIONS: The LANTERN system reduced assessments not indicated while improving family satisfaction and support for children, families and referrers. A senior-led, evidence-informed triage can enhance quality and efficiency in the autism diagnostic pathway.

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13. Grosvenor LP, Gunderson EP, Qian Y, Alexeeff S, Ames JL, Weiss LA, Sahagun E, Ashwood P, Yolken R, Zhu Y, Van de Water J, Croen LA. Prenatal Glucose Intolerance and Child Neurodevelopmental Disorders. JAMA Netw Open. 2025; 8(11): e2541657.

IMPORTANCE: Gestational diabetes has been associated with risk of neurodevelopmental disorders (NDD). An improved understanding of this association can inform prevention strategies and elucidate underlying mechanisms. OBJECTIVE: To determine associations between prenatal glucose intolerance and NDD and examine differences by gestational timing and child sex. DESIGN, SETTING, AND PARTICIPANTS: This population-based case-control study examined data from electronic health records from mother-child pairs in an integrated health system in northern California. Children born January 1, 2011, to December 31, 2018, and their mothers were eligible; children were followed up for outcomes through 2023. Data were analyzed from February 2024 to March 2025. EXPOSURES: Gestational diabetes was determined from routine prenatal test results and categorized as diagnosed early (less than 24 weeks), standard (24 to 28 weeks), or late (more than 28 weeks) in gestation. Prenatal subclinical impaired glucose tolerance (IGT) was defined by elevated glucose screening tests and neither GDM diagnosis nor treatment. MAIN OUTCOMES AND MEASURES: Autism spectrum disorder (ASD) and developmental delay were determined from medical records. Adjusted odds ratios (aOR) for associations between prenatal exposures and NDD were estimated using multivariable logistic regression models, adjusted for child sex, birth year, maternal age, race and ethnicity, education, parity, gestational age at prenatal care entry, and prepregnancy body mass index. Effect modification was evaluated by GDM diagnosis timing and sex. RESULTS: A total of 4546 mother-child pairs (median [IQR]) age of diagnosis: ASD, 3.0 [2.0-5.0] years; developmental delay, 2.0 [1.0-3.0] years; 2697 male children [59.3%]) were included in the study, of which 403 mothers (8.9%) had GDM and 64 (1.4%) had IGT; 683 children [15.0%] had ASD, 2054 [45.2%] had developmental delay, and 1809 [39.8%] were controls. GDM was not associated with increased odds of ASD (aOR, 1.15 [95% CI, 0.83-1.60]) or developmental delay (aOR, 1.24 [95% CI, 0.98-1.57]) overall. In sex-stratified analyses, GDM was associated with increased odds of ASD only among females (females: aOR, 2.05 [95% CI, 1.15-3.56]; males: aOR, 0.93 [95% CI, 0.62-1.37]; P for interaction = .04). When assessed by timing, early GDM was associated with increased odds of ASD among females (aOR, 3.23 [95% CI, 1.11-8.91]) but not among males (aOR, 0.78 [95% CI, 0.38-1.56]; P for interaction = .02). There were no associations between standard or late GDM and ASD in either sex. Prenatal IGT was associated with increased odds of developmental delay among females only (females: aOR, 3.25 [95% CI, 1.34-8.68]; males: aOR, 1.07 [95% CI, 0.50-2.39]; P for interaction = .08). CONCLUSIONS AND RELEVANCE: In this case-control study, GDM was associated with NDD in a gestational timing- and sex-specific manner. IGT associations with NDD were also sex-specific, adding to a body of research demonstrating influences of prenatal IGT on child outcomes.

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14. Gülbetekin E, Yıldırım Z. Digital Training Program with Mothers of Toddlers on Weaning, Toilet Training and Autism Knowledge: A Randomized Controlled Trial. J Community Health Nurs. 2025: 1-12.

PURPOSE: In recent years, research has emphasized the need to increase mothers’ awareness of important issues, particularly toilet training, breastfeeding termination training, and autism. The aim of this study is to increase the awareness levels of mothers through a training program on sensitive issues in the 18-36 months group, such as toilet training, autism and breastfeeding termination. DESIGN AND METHODS: The study was conducted as a randomized controlled trial. The study population consisted of 90 mothers with children aged 18 to 33 months living in a province in eastern Turkey between September 2024 and February 2025. A « Personal Information Form, » the « Toilet Training Knowledge Attitude Scale, » the « Autism Awareness Scale Mother Form, » the « Weaning Scale » and the « Informed Voluntary Consent Form » were used to collect the data. Animation-supported digital education prepared by the researchers was applied to the mothers in the experimental group for a duration of six weeks. FINDINGS: The difference between the knowledge levels of the experimental and control groups in terms of toilet training, autism awareness and breastfeeding termination after the training was found to be statistically significant (p < 0.05). The pre-post score difference between the experimental group and the control group was significantly higher in all groups. CONCLUSIONS: The animation-supported digital education given to the mothers in the experimental group was found to have a positive effect on their toilet training, autism awareness and breastfeeding termination knowledge levels. CLINICAL RELEVANCE: Nurses working and specializing in pediatrics and public health should explore ways to use technology-based training.

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15. Hamad IZ, Subhi HT, Abdul FR. Gut Pathogens and Cytokine Profiles in Autism: A Multi-Biosample Analysis. Apmis. 2025; 133(11): e70085.

To explore immune, microbial, and gene expression alterations in children with autism spectrum disorder (ASD), assessing their potential as diagnostic markers. Thirty participants, 20 with ASD (15 male, 5 female) and 10 healthy controls, underwent collection of saliva, blood, and stool. Serum cytokines (IL-1β, IL-6, IL-17A, TNF-α) were quantified via ELISA. RT-qPCR assessed corresponding gene expression in blood and saliva. Stool cultures yielded bacterial isolates identified by 16S rRNA sequencing methods. Diagnostic accuracy of cytokines was evaluated using ROC curves. Familial history revealed Down syndrome in 25% of ASD families. Stool cultures produced 31 isolates, predominantly Escherichia (23 E. coli, 5 E. fergusonii, including enterohemorrhagic strains). ASD patients exhibited significantly higher serum cytokine levels (mean ± SE, pg/mL): IL-1β 2275.9 versus 429.3; IL-6109.9 versus 47.6; IL-17A 1457.7 versus 963.6; TNF-α 367.2 versus 148.8 (p < 0.01). Cytokines were strongly intercorrelated, and ROC analysis showed excellent diagnostic potential. Gene expression mirrored serum findings, while salivary cytokine expression varied. Cytokine expression correlated closely with serum protein levels. ASD in this Iraqi cohort is characterized by strong pro-inflammatory signatures and microbial dysbiosis, with IL-6 and TNF-α emerging as potential biomarkers. These markers warrant further investigation for early diagnosis and targeted interventions.

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16. Huang Y, Huang Z, Wang Z, Tang W, Zhang X. The imperative for multigenerational genetic screening: A case report of fragile X-associated tremor/ataxia syndrome (FXTAS). Medicine (Baltimore). 2025; 104(42): e45411.

RATIONALE: Fragile X-associated tremor/ataxia syndrome (FXTAS), presenting with cognitive impairment as the initial symptom, is rare. This report emphasizes the need to consider FXTAS diagnosis in cases of early onset cognitive impairment in an aging population. PATIENT CONCERNS: A 57-year-old male with FXTAS was initially misdiagnosed with neuronal intranuclear inclusion disease, whose first manifestation was cognitive impairment. Testing showed a verbal IQ of 74, a performance IQ of 73, and a full scale of IQ 71, and a Clinical Memory Quotient of 74. Furthermore, his Mini-Mental State Examination score of 23 reflected a decline in short-term memory. Following reevaluation of imaging, identified T2-fluid attenuation inversion recovery hyperintensity at the cerebellar peduncles, and further investigation of the family history revealing a 7-year-old grandson with fragile X syndrome (FXS), repeat genetic testing of the patient demonstrated 121 CGG repeats in the FMR1 gene, confirming the diagnosis of FXTAS. DIAGNOSES: FXTAS. INTERVENTIONS: The patient was treated with donepezil and simvastatin daily and alcohol consumption was restricted. OUTCOMES: After 1 year, the patient showed partial improvements in memory, with his Mini-Mental State Examination score rising to 27, allowing him to resume employment as a community security guard. LESSONS: Due to the highly variable clinical presentation of FXS within families, clinicians should always consider fragile X testing and detailed family history when middle-aged and elderly males exhibit unexplained cognitive impairment or tremors. With the acceleration of aging in society, this case underscores the importance of multigenerational genetic screening for maternal grandparents, particularly males, in FXS families and prioritizing follow-up monitoring.

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17. Ingadottir TR, Jonsdottir H, Jarrett MA, Hannesdottir DK. Youth with ADHD, autism or comorbid ADHD and autism in Iceland: Comparisons of attentional and cognitive profiles and the effects of anxiety on cognitive performance. Res Dev Disabil. 2025; 167: 105142.

BACKGROUND: Attentional and cognitive profiles of youth diagnosed with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or co-occurring ADHD and ASD were examined in a large, nationwide clinical sample in Iceland. The impact of anxiety disorders on cognitive performance in this neurodiverse sample was also examined. METHODS: Clinical medical records at a government-run assessment center serving youth from all of Iceland comprised the study sample of 872 youth aged 7-18 years. All participants had been diagnosed with ADHD, ASD, or ADHD+ASD without intellectual impairment; of these, 239 youth were also diagnosed with co-occurring anxiety. All participants completed the Wechsler´s Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Conners Continuous Performance Test 3rd Edition (CPT-3) as part of their diagnostic process. RESULTS: Results indicated that children with ADHD+ASD performed better on the Perceptual Reasoning Index (PRI) on the WISC-IV compared with children with ADHD but showed no difference compared to the ASD only group. On the CPT, differences emerged for children with ADHD, who showed more variability in their performance compared with children with ASD or ADHD+ASD. Children with neurodevelopmental disorders (ADHD and/or ASD) and a co-occurring anxiety disorder performed worse on the Verbal Comprehension Index (VCI) on the WISC-IV. Still, they performed better on the CPT compared with children with neurodevelopmental disorders without anxiety. CONCLUSION: The findings reveal patterns of cognitive performance for children with ASD and/or ADHD with co-occurring anxiety disorders that need to be considered for appropriate accommodation in clinical, teaching and testing approaches for neurodiverse children.

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18. Kopańska M, Ochojska D, Sarzyńska I, Trojniak J, Szczygielski J. Exploratory quantitative EEG characteristics in children with autism spectrum disorder. Front Psychiatry. 2025; 16: 1689000.

INTRODUCTION: Autism Spectrum Disorders (ASD) are currently one of the most common childhood conditions. It is estimated that they affect approximately 1 in 31 children. Early and rapid diagnosis can increase a child’s chances of reaching full developmental, social, and educational potential despite their condition. METHODS: Our study aimed to describe a brainwave pattern in children with mild autism spectrum disorder (Level-1 according to DSM-5) based on quantitative electroencephalography (QEEG) analysis. The QEEG study is one of the valuable electrophysiological methods used in neurology and psychiatry, becoming more and more popular for diagnosing ASD. Our study included 48 children aged 7-10 years. Based on previous clinical examinations, 24 of them were diagnosed with mild ASD (mASD). Quantitative electroencephalography for Delta, Theta, Alpha, sensorimotor rhythm (SMR), Beta1, and Beta2 waves was performed using electrodes placed at thirteen recording points (frontal: FzF3F4, central: CzC3C4, parietal: P3PzP4, temporal: T3T4, and occipital: O1O2 points) with eyes open and closed. RESULTS: A comparison of the results between the mASD group and control group revealed significantly higher amplitude values for all Delta, Theta, Alpha, SMR, Beta1, and Beta2 wave measurements in the mASD population. Furthermore, the overrepresentation of Beta2-waves could be discerned in mASD children, as compared to their non-ASD-affected peers. DISCUSSION: The described pattern may help screen for mASD or confirm the diagnosis in the pediatric population of mASD-suspected patients. Additionally, it is worth noting that the results obtained demonstrate the importance of QEEG in detecting different patterns of brain activity in children with ASD, which plays a significant role in better understanding the heterogeneity of this disorder.

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19. Lacalamita A, Pantaleo E, Monaco A, Bellantuono L, Fania A, La Rocca M, Maggipinto T, Tangaro S, Amoroso N, Bellotti R. A joint complex network and machine learning approach for the identification of discriminative gene communities in autistic brain. PLoS One. 2025; 20(11): e0334181.

Autism is a genetically and clinically very heterogeneous group of disorders. Gene co-expression network analysis can help unravel its complex genetic architecture through the identification of communities of genes that are dysregulated. Using a publicly available brain microarray dataset (experiment GSE28475), we performed a gene co-expression analysis based on Leiden community detection to identify stable communities of genes and used them within a robust machine learning framework with feature selection. We reached an accuracy as high as [Formula: see text] in discriminating between autism and control subjects and validated our results on an independent microarray experiment obtaining an accuracy of [Formula: see text]. Furthermore, we found two communities of 43 and 44 genes that were enriched for genetically associated variants and reached an accuracy of [Formula: see text] and [Formula: see text] on the independent set, respectively. An eXplainable Artificial Intelligence analysis on these two causal communities confirmed the pivotal role of autism specific variants thus independently validating our analysis. Further analysis on the restricted number of genes in the identified communities may reveal essential mechanisms responsible for autism spectrum disorder.

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20. Lin S, Qi Y, Xie H, Sun X, Wang W, Jiang K. De novo frameshift mutation in SYNGAP1 resulting in autosomal dominant mental retardation type 5 and autism spectrum disorder: a case report. Front Pediatr. 2025; 13: 1671464.

BACKGROUND: Autosomal Dominant Intellectual Disability Type 5 (MRD5) is caused by heterozygous mutations in the SYNGAP1 gene. This gene, located on chromosome 6q21, encodes a synaptic Ras/Rap GTPase-activating protein that regulates Ras/Rap signaling and AMPA receptor trafficking, impacting synaptic plasticity and neuronal homeostasis. According to studies by Chen et al. and Kim et al., the SYNGAP1 gene is localized to dendritic spines of pyramidal neurons in the rodent neocortex. CASE SUMMARY: We report a 2-year-10-month-old girl presenting with global developmental delay (GDD) and autistic behaviors, characterized by unsteady gait, inability to stand on one foot, significantly impaired expressive language (maximally three-word phrases), poor response to name, reduced eye contact, and absent joint attention, despite normal hearing. Standardized assessments revealed severe impairments: Gesell Developmental Quotient (DQ) = 36, Childhood Autism Rating Scale (CARS) score = 42 (indicating severe autism), and Autism Diagnostic Observation Schedule (ADOS-2) Module 1 score = 16. Whole-exome sequencing identified a de novo heterozygous frameshift mutation in the SYNGAP1 c.1230delC p. (Ser410ArgfsTer30), classified as pathogenic per ACMG guidelines. Electroencephalography (EEG) revealed no abnormalities, and brain magnetic resonance imaging (MRI) showed no structural lesions. The patient was diagnosed with MRD5 and Autism Spectrum Disorder (ASD). CONCLUSION: We present a case of SYNGAP1-related MRD5 characterized by significant global developmental delay and autism spectrum disorder, featuring a novel c.1230delC frameshift variant that has not been reported before. This discovery expands clinicians’ knowledge of the mutation spectrum and phenotypic variability linked to SYNGAP1, enhancing understanding of genotype-phenotype relationships in SYNGAP1-related conditions.

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21. Park SK, Cho JH, Lee H, Kim SH. Patterns of social participation among people with developmental disabilities and associated factors in South Korea. Res Dev Disabil. 2025; 167: 105138.

BACKGROUND: Despite growing interest in expanding the scope of social participation from passive to active, few studies have empirically examined participation patterns among people with developmental disabilities (DD), particularly in South Korea. OBJECTIVE: This study aimed to (1) identify latent classes of social participation among individuals with DD and (2) examine demographic, physiological, and psychosocial characteristics associated with each class. METHODS: We analyzed data from the 2020 Survey of Work and Life with Developmental Disabilities in South Korea (N = 3000). Latent Class Analysis (LCA), using 14 indicators of social participation, identified subgroups. Subsequently, multinomial logistic regression examined the associations between class membership and demographic, physiological, and psychosocial characteristics. RESULTS: The LCA identified four social participation classes: (1) active involvement (21.8 %), characterized by high functioning and diverse social engagement; (2) moderately active involvement (11.6 %), with relatively high engagement in cultural and leisure activities despite lower ADL/IADL functioning and self-determination; (3) passive involvement (40.1 %), with low social participation despite fewer daily functioning difficulties; and (4) social exclusion (26.5 %), marked by major difficulties in both daily and social activities. Multinomial regression analysis showed that the active or moderately active involvement classes were more likely to report individuals aged 10-30, with a college education, high smartphone proficiency, good health, mild disabilities, and high family support than the social exclusion class. Interestingly, the moderately active involvement class was more likely to be teens and at risk of discrimination compared to the social exclusion class, while the passive involvement class was more likely to be over 40 compared to the other three classes. CONCLUSIONS: These findings highlight the importance of considering the unique characteristics of each class in effectively promoting active social participation among individuals with DD.

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22. Rajagopalan K, Rashid N, Doshi D, Gopal D. Predictors of aspiration, lower respiratory tract infection, and respiratory failure among individuals with Rett Syndrome: analysis of real-world claims data in the United States. Front Pediatr. 2025; 13: 1681103.

BACKGROUND: Rett (RTT) syndrome, a rare, neurodevelopmental disorder affects multiple organ-systems (i.e., gastrointestinal, respiratory), with diverse clinical manifestations. While gastrointestinal manifestations are well-known, respiratory manifestations [i.e., aspiration, lower respiratory tract infection (LRTI), and respiratory failure (RF)] and associated predictors are not well-studied. This real-world data analysis evaluated the predictors of aspiration, LRTI, and RF among RTT individuals in the United States. METHODS: A retrospective database analysis using IQVIA’s Anonymized Patient Level database from 08/01/2020 to 03/31/2023 was conducted to identify newly diagnosed RTT individuals with ≥1 RTT diagnostic claim (ICD-10-CM: F84.2) between 02/01/2021 and 03/31/2022. Index date was the first RTT diagnostic claim. Eligible sample included individuals with 6-months pre-index and 12-months post-index follow-up, as well as no pre-index cerebrovascular disease or brain trauma diagnosis. Predictors of aspiration, LRTI, and RF were separately evaluated using exploratory backward selection models followed by confirmatory multivariable logistic regressions and reported using odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Of the 1,994 with RTT, 7.27% (n = 145), 9.48% (n = 189), and 10.08% (n = 201) experienced post-index aspiration, LRTI, and RF, respectively. Significant predictors for aspiration were cough [3.39 (1.82-6.29)], dysphagia [3.04 (1.86-4.99)], LRTI [2.34 (1.22-4.51)], and neurological disorders (i.e., epilepsy/convulsions) [1.77 (1.18-2.66)]; LRTI were respiratory disorders [4.06 (2.63-6.27)], RF [3.02 (1.65-5.53)], neurological disorders [1.57 (1.07-2.29)], infections [1.69 (1.04-2.80)], and gastrointestinal disorders [1.57 (1.04-2.37)]; RF were LRTI [4.70 (2.58-8.58)], respiratory disorders [3.38 (2.23-5.13)], dysphagia [2.73 (1.73-4.31)], gastrointestinal disorders [2.09 (1.40-3.10)], musculoskeletal disorders [1.86 (1.01-3.40)], and neurological disorders [1.69 (1.16-2.45)]. Confirmartory models showed similar results. CONCLUSION: Baseline neurological and respiratory disorders were common predictors of aspiration, LRTI, or RF. Additional predictors included gastrointestinal disorders for LRTI and RF; and musculoskeletal disorders for RF only. These real-world findings can help inform evidence based clinical decision-making for management of RTT.

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23. Schmarder KM, Axelrod DB, Agarwal R, Sangoi JA, Jaisle EM, Mulet K, Sabates LR, Laird AR, Musser ED. Practices of Self-Advocacy and Their Implications From the Perspectives of Transition-Age, Young Adults With Intellectual and/or Developmental Disabilities. J Autism Dev Disord. 2025.

PURPOSE: The purpose of the study is to characterize the practices of self-advocacy, as well as their impact on family life, among transition-age adults with intellectual and/or developmental disabilities (IDD; i.e., autism, intellectual disability) enrolled in an inclusive post-secondary education (IPSE) program. Researchers centered young adult voices, which in academic discourse have been traditionally marginalized in favor of centering voices of parents. METHODS: Focus groups with participants (n = 29) elicited perspectives on programmatic elements, practices of self-advocacy, and student-parent relationships. RESULTS: Findings highlighted student perspectives that: (1) caring for yourself and speaking up/standing up for yourself are both practices of self-advocacy; (2) understanding their own roles and context, self-confidence, and the openness of the person they were self-advocating to may serve as facilitators or barriers to self-advocacy; (3) parents have a role in introducing and reinforcing self-advocacy skills for young adults; and (4) relationships with their families changed during involvement in the IPSE program, with some reporting use of self-advocacy skills as a point of conflict with their parents. CONCLUSION: Young adults with IDD report unique practices of self-advocacy such that they include caring for oneself as self-advocacy. Centering their voices may help inform how to best support their transition to independence and facilitate self-advocacy on small (e.g., with family and peers) and large (e.g., with organizations and policy) scales.

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24. Shimono K, Kashida N, Nishigori K, Iwasaki T, Mizui R, Yamamuro K, Ishida R, Toritsuka M, Takeda T, Tanakoshi H, Nagata H, Iwata N, Makinodan M. Comparative study of ERP habituation to tones and fearful vocalizations in autism spectrum disorders: a translational biomarker for sensory hypersensitivity. Mol Psychiatry. 2025.

Sensory issues are common in autism spectrum disorders (ASD) and can significantly affect daily living. The phenomena of gating and habituation of event-related potentials (ERPs) to repetitive stimuli have been suggested as potential biomarkers reflecting atypical sensory processing in ASD. Sensory hypersensitivity and anxiety are closely related in ASD, and habituation to emotionally evocative stimuli may serve as a more sensitive biomarker for sensory hypersensitivity symptoms. However, previous studies have primarily used tonal stimuli, and there has been little investigation into whether habituation to emotionally evocative sounds is impaired in ASD patients. In this study, we compared the degree of habituation of the P1-N1 peak-to-peak amplitude in response to repeated tones and fearful vocalizations between control and ASD groups. Contrary to expectations, no significant difference was observed for fearful vocalizations between the groups, while ASD patients showed significantly reduced habituation to tonal sounds in the left parieto-occipital region. Furthermore, we found a significant correlation between the degree of habituation to tonal sounds in the left parieto-occipital region and sensory hypersensitivity symptoms in ASD patients, and similar abnormalities in BTBR mice, an animal model of ASD. These results suggest that habituation to tonal sounds, rather than emotionally evocative stimuli, may serve as a translational biomarker reflecting sensory hypersensitivity symptoms.

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25. Solgi CA, Debnath S, Chandran S. Exploring the Association of Parenting Styles on Behavioral Outcomes in Children with Autism Spectrum Disorder: A Cross-sectional Study. Indian J Psychol Med. 2025: 02537176251385242.

BACKGROUND: Parenting styles shape behavioral outcomes in children with autism spectrum disorder (ASD), yet their influence in low-resource settings, such as India, remains underexplored. This study investigates how parenting styles (authoritative, authoritarian, and permissive) correlate with behavioral outcomes in children with ASD in India, and examines demographic influences. METHODS: A cross-sectional study was conducted with 82 parents of children with ASD (aged 3-17 years) at a tertiary care hospital. Parenting styles (authoritative, authoritarian, and permissive) were assessed using the Parenting Styles and Dimensions Questionnaire (PSDQ), and behavioral problems were measured with the Strengths and Difficulties Questionnaire (SDQ). Descriptive statistics, Pearson correlation, analysis of variance (ANOVA), and t-tests were applied. RESULTS: Authoritative parenting predominated (mean score: 57.33 ± 9.55), linked to fewer behavioral challenges, while authoritarian (r = 0.37, p < .001) and permissive (r = 0.34, p = .002) styles were associated with increased difficulties, notably hyperactivity (6.66 ± 1.67) and peer problems (5.09 ± 1.83). Higher parental education favored authoritative practices (p = .007), whereas prolonged treatment duration worsened behaviors (p = .003). CONCLUSION: Authoritative parenting mitigates behavioral challenges in children with ASD, unlike authoritarian and permissive styles, which exacerbate difficulties. These findings underscore the need for culturally tailored interventions such as workshops addressing stigma, resource scarcity, and language barriers to promote adaptive caregiving in India. Policymakers should integrate parental education into ASD care to enhance family well-being.

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26. Song Y, Shen B, Pang Y, Dong L. Relationships between physical activity and quality of life in parent-child dyads with ASD. Front Psychol. 2025; 16: 1669728.

INTRODUCTION: Autism spectrum disorder (ASD) is characterized by core and associated symptoms that adversely affect the quality of life (QOL) of both children with ASD and their parents. Although physical activity (PA) has been shown to promote QOL and well-being, limited research has examined these associations within parent-child dyads in families affected by ASD. METHODS: This cross-sectional study recruited 85 parent-child dyads from two autism rehabilitation centers in Central China. Children had a mean age of 5.25 years, and 75.3% of parents were aged between 31 and 40 years. Partial Pearson correlation analyses were conducted to examine associations between children’s and parents’ PA levels and multiple domains of QOL, controlling for child age, sex, and symptom severity. RESULTS: Significant reciprocal associations were observed between the PA levels of children with ASD and their parents. Specifically, children’s light-intensity physical activity (LPA) was positively associated with parents’ LPA (r = 0.351, p < 0.01) and with the psychological (r = 0.23, p < 0.05) and environmental (r = 0.26, p < 0.05) domains of parental QOL. No direct correlations were identified between parental PA and children's QOL. DISCUSSION: These findings underscore the potential of LPA as a feasible and accessible form of joint activity that may support QOL within families of children with ASD. Framed through reciprocal determinism, the results highlight the interconnected roles of children's PA (behavior), parents' psychological well-being (personal factor), and the family context (environment). Further longitudinal and intervention studies are warranted to confirm these relationships and inform family-centered PA interventions.

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27. Warrick JE, Attili D, van Eeuwen T, Pastore B, Hoffmann-Weitsman SE, Forsyth NC, Tang W, Barmada SJ, Kearse MG. An autism spectrum disorder mutation in Topoisomerase 3β causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain. Nucleic Acids Res. 2025; 53(20).

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

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28. Wong IHW, Ng SM, Lam AMW, Chan SSM, Ng SH, Leung J, Lee KCL, Wong ACC, Wu Y, Chan FKL, Ng SC, Wong OWH. The Distinctive Clinical Profiles of Children With Autism Suffering From Different Subtypes of Rome IV Functional Gastrointestinal Disorders. Autism Res. 2025.

Functional gastrointestinal disorders (FGIDs) are prevalent in children with autism and can interact with the neuropsychiatric symptoms bidirectionally. Moreover, FGIDs may affect feeding to jeopardize nutritional intake. Existing research often overlooks the heterogeneity of FGIDs. Understanding the clinical correlates of individual FGID subtypes may clarify the underlying gut-brain interactions to guide management. This study compared the core autistic symptoms, co-occurring psychopathologies, feeding behavior and dietary intake among 737 Chinese children with autism (mean age = 7.76 years; 642 males and 95 females) who either experienced no FGID or experienced one of the three subtypes of ROME-IV FGID. FGIDs were present in 19.8% of participants and MANCOVA revealed distinct clinical profiles across FGID subtypes. Functional abdominal pain disorders (FAPD) were associated with more severe neuropsychiatric symptoms, including restricted and repetitive behavior, anxiety, sensory hyperresponsiveness, externalizing behavior, and feeding patterns of emotional under-eating, slowness in eating, and increased satiety response. Functional defecation disorders (FDD) were characterized by food fussiness, slowness in eating, increased satiety response, and decreased intake of water, protein and fiber. With a small sample size of six, functional nausea and vomiting disorders (FNVD) were associated with emotional overeating. These findings suggest FGID subtypes involve distinct gut-brain interactions. Sensory dysregulation may underlie the link between FAPD and neuropsychiatric symptoms, while food fussiness in FDD may contribute to constipation via reduced fiber and water intake. The management of FGIDs in autism should be tailored to specific subtypes and their clinical correlates.

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29. Yoon S, Lee S, Kwon H, Kim HS, Joo JH, Hong S, Kim SY, Jang S, Lee H, Choi HS, Cho A, Jeong S, Suh-Yun Joh C, Oh H, Choi EH, Choi M, Ahn K, Kim HJ, Kim KP, Chae JH. Biallelic BRF2 mutations disrupt redox homeostasis as etiological factors in syndromic immunodeficiency and developmental disorders. Mol Ther. 2025; 33(11): 5661-80.

TFIIB-related factor 2 (BRF2) is a critical component in the recruitment of RNA polymerase III (RNA Pol III) to type III promoters containing a TATA box. These promoters regulate the expression of key elements such as U6 spliceosomal RNA, the tRNA processing enzyme RNase P, and selenocysteine tRNA. Despite the essential role of BRF2, the genetic disorders associated with BRF2 mutations and their molecular pathogenesis remain poorly defined. In this study, we identified and characterized novel biallelic BRF2 variants with impaired RNA Pol III activity in a familial case presenting with multisystem anomalies, malignancy, and primary immunodeficiency. Whole-exome sequencing revealed compound heterozygous BRF2 variants predicted to disrupt interaction with the TATA box-binding protein. Subsequent gene expression profiling of the patient’s whole blood cells using single-cell RNA sequencing was conducted. Clinically, the patient exhibited recurrent infections and hypogammaglobulinemia in early childhood, which improved over time but was followed by the development of low-grade B cell lymphoma during adolescence, necessitating chemotherapy. Functional analyses in human cells expressing the BRF2 variants demonstrated defective BRF2-dependent RNA Pol III transcription of redox-regulating genes, specifically GPX1 and GPX4. These findings establish a pathogenic link between BRF2 dysfunction and disrupted redox homeostasis, offering mechanistic insights into the hemato-immunological and developmental abnormalities observed in affected individuals and highlighting potential implications for clinical management.

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30. Zhang D, Zhou M, Qiu Y, Xu H, Liu H, Liu Y, Xie L. Cross-generational mechanisms of maternal gut microbiota in modulating offspring autism spectrum disorder risk: from the gut-brain axis to translational challenges in precision interventions. Front Aging Neurosci. 2025; 17: 1642240.

Autism Spectrum Disorder (ASD) manifests as a group of neurodevelopmental disorders with high clinical and genetic heterogeneity, characterized by core features including social communication deficits, repetitive behaviors, and restricted interests. Current research primarily focuses on genetic variations, immune dysregulation, synaptic dysfunction, and gene-environment interactions. Nowadays, accumulating evidence indicates that maternal gut microbiota dysbiosis, induced by high-fat diets, antibiotic overuse, and urbanization, significantly correlates with abnormal fetal neurodevelopment and increased ASD risk. This review systematically delineates three transplacental mechanisms whereby maternal dysbiosis regulates fetal neurodevelopment: Metabolite-mediated pathways, Immune pathway activation, and Epigenetic reprogramming. Meanwhile, the key translational challenges are highlighted. At last, metagenomics-metabolomics-fetal neuroimaging, Development of microbiota metabolite-treated brain organoids, and Artificial Intelligence-driven (AI-driven) probiotic screening were proposed as research directions in future.

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