1. Batista DM, Oliveira ARP, Nogueira LRD, Silva L, Nascimento RND, Cardoso AM, Goulart EV, Ferreira MGS. Experiences of mothering children with autism spectrum disorder. Rev Gaucha Enferm. 2026; 47: e20250216.

OBJECTIVE: to investigate the challenges faced and the strategies adopted by mothers of children with autism spectrum disorder in the experience of mothering. METHOD: a descriptive study, with a qualitative approach, was supported by the Sensitive Creative Method, using the « Tree of Knowledge » dynamic. It was conducted in July 2024 in a room at the State University of Pará. Thirteen mothers of children with the disorder participated. The data were subjected to French Discourse Analysis. RESULTS: the process of caring for a neuroatypical child begins with maternal perception of the first signs of atypicality, triggering a lonely and painful search for explanations. The difficulties faced involve the lack of preparation of health professionals, the high cost and slowness of diagnosis, as well as feelings such as guilt, denial and despair. However, over time, mothers develop internal strategies (patience, love, faith, resilience and knowledge) and external strategies (support network, therapies, medications) that strengthen the exercise of motherhood. FINAL CONSIDERATIONS: the impacts of the disorder result in the redefinition of the mothering process. It is necessary to give visibility to the demands of these mothers, promote spaces for qualified listening and to train health professionals, essential to promote quality of life for mothers, children and the dynamics of maternal care.

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2. Chen S, Qiu Z, Peng Q, Liu L, Wu Y, Li Y, Zhang C, Yang X, Ma P. A potential risk of plastic and plasticizer pollution: a molecular toxicological study on DIDP-exacerbated autism-like behaviors in juvenile mice. Toxicol Res (Camb). 2026; 15(1): tfaf168.

Plastic pollution and childhood health are two significant public health issues worldwide. However, there is a lack of corresponding toxicological studies to confirm this association, and the molecular pathological mechanism behind it remains unknown. Here, we utilized DIDP as a proxy to examine the association. A mouse model of autism-like behaviors was successfully constructed using the early social deprivation (ESD) approach. Social deficits were evaluated through the three-chamber social preference test, while cognitive impairments were assessed using the Morris water maze test. Various metrics, including oxidative stress (ROS, GSH, MDA, and 8-OHdG), inflammatory response (IL-6/TNF-α), and pathological impairments in brain tissue, were examined. Additionally, we explored the mediation of oxidative stress signaling pathways as molecular pathological mechanisms and investigated the preventive and therapeutic effects of vitamin E (VitE) on social disorders. The results indicate that mice exposed to the plasticizer DIDP exhibited oxidative stress, pathological damage, and inflammatory responses in the hippocampal region of the brain. Additionally, behavioral tests revealed that these mice displayed social deficits and cognitive impairments. However, upon administration of VitE, the mice exhibited significant improvement in social deficits and cognition impairments. The study finds that exposure to the plasticizer DIDP exacerbates autism in mice, possibly through the molecular pathological mechanisms of oxidative stress and inflammation in brain tissue. Furthermore, VitE is found to have a noteworthy protective effect against the worsening of autism caused by exposure to the plasticizer DIDP.

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3. Day M, Scargill K, Poole D, Kellar I, Young TA, Bölte S, Clarke S, Lodge KM, Woods A, Freeth M. Feasibility of the ICF CoreSets for Autism Strengths and Needs Assessment in NHS diagnostic services in England: protocol for a randomised pilot trial. BMJ Open. 2026; 16(3): e103303.

INTRODUCTION: There are approximately 700 000 autistic people in the UK, and autism is increasingly being diagnosed in adulthood. Diagnosis on its own does not provide adequate information to plan post-diagnostic support for autistic people, and clinicians often plan support without the use of validated standardised tools which may exacerbate inequities in care. This study will evaluate a novel strengths and needs assessment, based on the WHO’s International Classification of Functioning, Disability and Health CoreSet for Autism, for use in adult diagnostic services immediately on receipt of an autism diagnosis. Potential issues, including the length of the assessment, timing of delivery and selection bias, will be explored as part of the trial process evaluation. METHODS AND ANALYSIS: A two-arm, multisite, randomised pilot trial design will be used to evaluate the ICF CoreSets for Autism Strengths and Needs Assessment in three diagnostic services in England. A total of 72 newly diagnosed autistic adults will be recruited across the three sites over a 6-month period and randomised into an assessment group (strengths and needs assessment plus standard care) and a treatment as usual group (standard care only). The assessment group will receive a summary report of their strengths and needs on completion of the assessment. Both groups will complete measures of mental health and quality of life at baseline and 3 months follow-up (Patient Health Questionnaire-9, Generalised Anxiety Disorder questionnaire-7, Recovering Quality of Life questionnaire-10, EuroQoL-5D). Acceptability and feasibility will be measured for the strengths and needs assessment and for trial procedures using standardised measures, progression criteria and qualitative data from clinician focus groups and interviews with a subsample of autistic participants. The study design and procedures are being co-produced with an autistic advisor/patient and public involvement lead and with a steering group of autistic adults. ETHICS AND DISSEMINATION: This study was reviewed by the East Midlands-Nottingham 2 Research Ethics Committee and was given Health Research Authority approval on 18 March 2025 (REC reference:25/EM/0041). The results will be disseminated via reports to the funder (NIHR), a peer-reviewed journal paper and academic conferences. We will email a summary report of findings to study participants and will invite participants to an information dissemination event at the end of the study. Links to reports and a lay summary will be provided on the research group’s website: https://sharl.sites.sheffield.ac.uk/home TRIAL REGISTRATION NUMBER: ISRCTN10283350.

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4. Hausler S, Sargeant K, George E. Understanding health services and puberty for autistic adolescents and those with disability: A scoping review to inform occupational therapy practice. Aust Occup Ther J. 2026; 73(2): e70079.

INTRODUCTION: Puberty is a transitional period presenting challenges for autistic adolescents, adolescents with disabilities and their families. There are opportunities for occupational therapy to provide support to this cohort as adolescents navigate the complexity of puberty transition. However, there is a lack of published evidence and knowledge translation to guide practice. It is important to scope the literature to gain understanding of the pubertal experiences of autistic adolescents, adolescents with a disability, their families and services accessed for support. The aim of this scoping review was to determine the current role and practice of health professionals supporting autistic adolescents and/or adolescents with disability and their families through puberty, to inform occupational therapy practice. METHODS: A scoping review was conducted following JBI protocols. Four databases were searched systematically. Key search terms included health professions, terminology for the stages and process of puberty, and neurodevelopmental disorders and disabilities. Eligible articles included literature published within the last 20 years, focused on the experience or recollection of people with disabilities undergoing puberty and experience of parents, caregivers or health professionals who support them. CONSUMER AND COMMUNITY INVOLVEMENT: There was no direct consumer or community involvement within this scoping review. FINDINGS: After screening 795 articles, 90 full texts were reviewed, and 17 were retained. Studies included a range of health professions, with two studies focused solely on occupational therapy. Themes identified included (1) challenges experienced by adolescents; (2) parental concerns and caregiver burden; (3) the importance of education for clients, caregivers and families; and (4) perspectives and practice of health professionals. CONCLUSION: Autistic adolescents and people with disability experience additional challenges during puberty and require additional support needs. There is a lack of literature focusing specifically on the role of occupational therapy in this field. Evidence from health services can more broadly inform and guide future direction for occupational therapy practice. There is a need for puberty-focused training for allied health professionals and an opportunity for occupational therapy to position itself at the forefront of evidence-based, family-and-client-centred practice in puberty-related care. We reviewed current information to learn how autistic young people and people with disabilities manage puberty and to find out more about health services for these young people and their families. We wanted to find out if puberty is more challenging for young autistic people than for people without autism and how occupational therapists support autistic people during puberty. We searched for recent articles but discovered there was not much information available. We expanded our search to also look for information about how puberty affects young people with a wider range of disabilities and for broader information about the supports people need. We learned that puberty is a tricky time and more challenging for autistic young people and people with disability. Occupational therapists and other health professionals can provide help, but there is not a lot of helpful information or training for them, and people are uncomfortable talking about puberty. We need to learn more about how to best support autistic adolescents, those with disabilities, their families and caregivers, and the health professionals who work with them. eng.

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5. Ismael HM, Ismail PA. Serum levels of TNF-α, IFN-γ, NGF, and CNTF in children with autism spectrum disorder. J Neuroimmunol. 2026; 415: 578899.

The etiopathogenesis of autism spectrum disorder (ASD) remains incompletely understood but involves dysregulation across multiple biological systems, including pro-inflammatory cytokine networks and neurotrophic signaling pathways. This study measured serum concentrations of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), alongside neurotrophic factors nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF), in children diagnosed with ASD compared to neurotypical controls. A secondary aim was to examine associations with ASD symptom severity. Participants included 60 children with ASD (86.7% male, mean age 9.4 ± 0.6 years) and 29 controls (79.3% male, mean age 8.0 ± 0.4 years), ASD severity was classified per DSM-5-TR criteria (Level I: n = 19; Levels II-III: n = 41). Serum analyses revealed elevated TNF-α (p = 0.048), NGF (p = 0.045), and CNTF (p = 0.032) in the ASD group compared to controls, with IFN-γ showing a non-significant increase (p = 0.279). However, biomarker levels showed no significant differences across ASD severity subgroups (Level I vs. Levels II-III vs. controls; all adjusted p > 0.14 following multiple testing correction). Spearman correlations demonstrated positive associations between all four biomarkers and ASD symptom severity scores (all p = 0.0001). In conclusion, the findings demonstrate altered serum profiles of selected inflammatory and neurotrophic markers in children with ASD and highlight strong interrelationships among these biomarkers. Although no significant associations with symptom severity were identified, the results support the involvement of dysregulated neuroimmune and neurotrophic signaling in ASD pathophysiology and warrant further investigation in larger, longitudinal studies.

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6. Kaan H, Coskun M. Autism Spectrum Disorder in a Child with Floating-Harbor Syndrome: A Case Report. Noro Psikiyatr Ars. 2026; 63: 299-301.

INTRODUCTION: The genetic basis of autism spectrum disorder (ASD) is highly heterogeneous and continues to be elucidated through syndromic associations. Floating-Harbor Syndrome (FHS) is a rare genetic disorder caused by SRCAP mutations and is characterized by short stature, expressive language delays, and distinct craniofacial features. This report aims to present the diagnostic process and clinical challenges of a child diagnosed with both FHS and ASD. CASE: A 9-year-old boy presented with social communication difficulties, restricted interests, and sensory hypersensitivity. Psychometric testing demonstrated average intellectual functioning (. IQ: 94), while behavioral assessments revealed significant hyperactivity and behavioral dysregulation, in addition to severe autism as measured by the Childhood Autism Rating Scale (CARS). Based on DSM-5 criteria, he was diagnosed with ASD. Persistently elevated amylase and lipase levels prompted genetic evaluation, which confirmed FHS with an SRCAP mutation. DISCUSSION: This case underscores the diagnostic challenges of differentiating syndrome-specific features from true comorbid ASD when overlapping symptoms such as language delay and behavioral problems are present. These findings highlight the importance of comprehensive psychiatric and genetic evaluation in children with complex developmental profiles, and highlights the need for systematic screening for neurodevelopmental disorders in rare genetic syndromes.

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7. Martins B, Martins J, Castelo-Branco M, Gonçalves J. Sex-dependent dysregulation of the gut-brain NPYergic system in a mouse model of autism spectrum disorder. Sci Rep. 2026.

The microbiome-gut-brain axis has been increasingly recognized for its role in the pathophysiology of autism spectrum disorder (ASD), yet the underlying molecular mechanisms remain poorly understood. Neuropeptide Y (NPY), a key modulator of gut-brain communication, may play a pivotal role in this axis. This study investigated the sex-specific molecular profile of the NPY system in gut-brain communication via a genetic mouse model of ASD, the Nf1(+/-) mice. Quantitative real-time PCR was performed to assess the expression of NPY and its receptor transcripts in the amygdala, hippocampus, prefrontal cortex and intestinal tissue of juvenile male and female Nf1(+/-) mice. Additionally, gut microbiota analysis focused on Lactobacillus species in stool samples. Special emphasis was placed on sex differences, an area underexplored in ASD research. Sex-specific differences in NPY and its receptor expression were observed in both the brain and intestinal tissues of Nf1(+/-) mice. In mutant females, estrous cycle fluctuations were partly associated with changes in the NPY system. Notably, distinct correlations between the brain and intestinal NPY systems were identified in both sexes of wild-type (WT) and Nf1(+/-) mice. Microbiota analysis revealed sex-dependent alterations in Lactobacillus abundance, which correlated with the intestinal NPY system. Importantly, the Y2 receptor exhibited sex-specific expression patterns in both the gut and brain of Nf1(+/-) mice. This study provides novel evidence that the NPY system may play a critical role in gut-brain communication in ASD, with sex-dependent alterations in both the brain and gut. The intestinal Y2 receptor has emerged as a potential molecular biomarker for ASD, underscoring the importance of incorporating sex as a biological variable in future ASD research.

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8. Mohammedsaeed W, Alharbi M. Network-Based Prioritization of Network-Peripheral Gene Modules in Autism Spectrum Disorder Using Integrative Transcriptomic and Proteomic Data. J Mol Neurosci. 2026; 76(1).

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9. Nautiyal H, Roy KK, Dwivedi S. BDNF- Dysregulation as a Neurobiological Bridge between Polycystic Ovarian Syndrome and Autism Spectrum Disorder. ACS Chem Neurosci. 2026; 17(5): 870-85.

Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder characterized by hyperandrogenism, has been increasingly associated with a high risk of autism spectrum disorder (ASD) in offspring. The emerging interaction between reproductive endocrinology and neurodevelopmental biology suggests that excessive androgen exposure during gestation may perturb neurotrophic signaling and impair neural circuit formation. Brain-derived neurotrophic factor (BDNF) acts through tropomyosin receptor kinase B receptor to activate downstream phosphoinositide 3-kinase/protein kinase B and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways, both of which are fundamental to neuronal survival and synaptogenesis. Disruption of these signaling cascades under hyperandrogenic conditions may lead to altered neuroarchitecture, impaired synaptic connectivity, and ASD-like behavioral phenotypes. Clinical and experimental studies also implicate aberrant BDNF expression in ovarian dysfunction, oocyte maturation deficits, and placental steroidogenic imbalance, highlighting a shared endocrine-neurodevelopmental axis in PCOS. Moreover, androgen excess may induce epigenetic modifications and post translational alterations of BDNF or tropomyosin receptor kinases B receptors, further compromising downstream signaling. These molecular events can dysregulate the transcriptional control of multiple synaptic and neurodevelopmental genes, thereby promoting atypical neuronal circuit formation. Understanding the interaction between BDNF signaling and androgen excess provides a mechanistic framework to explain how maternal endocrine imbalance influences neurodevelopment of offspring. This review integrates multidisciplinary findings spanning clinical cohorts, animal models, and molecular studies to delineate how androgen-BDNF interactions amplified by epigenetic, transcriptional, and post translational dysregulation underpin key neurodevelopmental disruptions observed in ASD. Furthermore, it emphasizes the translational potential of targeting BDNF-related pathways as early biomarkers or therapeutic entry points to mitigate the intergenerational neurodevelopmental consequences of PCOS.

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10. Niu M, Wang D, Jia S. Identification of a Homozygous PGM2L1 Variant in a Male Patient With Developmental Delay and Seizures. Mol Genet Genomic Med. 2026; 14(3): e70195.

BACKGROUND: PGM2L1 gene variants are associated with developmental delays, seizures, and various neurological and physical symptoms. This study aims to report the clinical features and genetic findings in a male patient with developmental delay, regression, and seizures. METHODS: Whole-exome sequencing (WES) was performed on the patient to identify the genetic etiology of the patient. Sanger sequencing was used for variant confirmation. Clinical evaluations were conducted, including cerebrospinal fluid analysis, cranial MRI, EEG, and neurological assessments. RESULTS: The patient is a 1-year-old male who presented with psychomotor delays and developed seizures and impaired consciousness at 1 year of age. Cranial MRI revealed bilateral frontotemporal subarachnoid widening. Developmental regression was observed shortly after the onset of seizures. The EEG results showed diffuse slow background activity and epileptiform discharges. WES identified a rare homozygous variant in the PGM2L1 gene (OMIM: 611,610, NM_173582.6: c.1673delC, p.Thr558Ilefs*19), which was inherited from both parents. Sanger sequencing confirmed the presence of the variant, and it was evaluated as a likely pathogenic variant according to American College of Medical Genetics and Genomics (ACMG) guidelines. CONCLUSION: Our study was the second report of a PGM2L1 gene variant associated with early-onset developmental delay and seizures, further expanding the genetic spectrum of this disorder.

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11. Osama TA, Hori YS, Vanleuven J, Persad AR, Ustrzynski L, Emrich SC, Tayag A, Purger D, Park DJ, Chang SD. Neuromodulation for treatment resistant autism: systematic review. J Clin Neurosci. 2026; 148: 111970.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social-communication impairment, restricted interests, repetitive behaviors, and, in a subset of individuals, severe aggression, self-injurious behavior (SIB), and obsessive-compulsive symptoms. Traditional behavioral and pharmacological approaches often provide limited benefit. Neuromodulation and ablative neuropsychiatric procedures have emerged as potential therapeutic strategies targeting the neural circuits implicated in ASD. OBJECTIVE: To systematically review the existing clinical literature on neuromodulatory and neurosurgical interventions for ASD, including deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS), transcranial direct current stimulation (tDCS), low-frequency electromagnetic stimulation, and stereotactic radiosurgery. METHODS: A comprehensive search of PubMed, Embase, and Cochrane Library was performed from inception through December 2025. Studies were included if they involved individuals with ASD undergoing any neuromodulation or ablative procedure and reported clinical outcomes. RESULTS: Sixteen studies met inclusion criteria. DBS targeting the nucleus accumbens, amygdala, or internal capsule produced substantial reductions in aggression, SIB, and obsessive-compulsive symptoms, with long-term improvements observed for up to several years. rTMS and iTBS targeting the pSTS, DLPFC, or medial prefrontal regions improved social responsiveness, emotion recognition, and aspects of executive function with minimal adverse effects. tDCS demonstrated benefits for social cognition, executive functioning, and behavioral regulation. Radiosurgery targeting limbic structures resulted in durable reductions in pathological aggression in highly refractory cases. Across modalities, adverse events were mild and transient. CONCLUSIONS: Neuromodulatory and ablative interventions demonstrate promising therapeutic potential for individuals with treatment-resistant ASD, particularly those with aggression, SIB, and profound social-cognitive deficits.

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12. Ousta GS, Adamopoulos C, Piperi C. Neurodevelopmental Impact of Advanced Glycation End Products in Children with Autism Spectrum Disorder. ACS Chem Neurosci. 2026; 17(5): 886-98.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with compromised prognosis and treatment. Current research has shown that along with genetic factors, maternal health, environmental exposures, and epigenetic modifiers play a critical pathogenic role. Emerging scientific evidence reveals the significant impact of increased advanced glycation end products (AGEs) in impairing pediatric brain development that may contribute to ASD by inducing neuroinflammation and oxidative stress through activation of the receptor for AGEs (RAGE) signaling in neuronal cells. Accumulation of AGEs has been shown to disrupt the blood-brain barrier (BBB) integrity, which is crucial for protecting the developing brain from harmful substances, as well as interfering with the vascular function and blood flow, affecting brain maturation, and inducing neuroendocrine dysregulation. In this review, we describe the impact of AGEs on pediatric brain development and synaptic plasticity, critical for learning and memory, as well as their input in exacerbating neuroinflammation through microglia activation, contributing to the development of autism-related neuropathology. We further discuss the diagnostic and patients’ stratification potential of specific AGE types as well as current interventions to reduce their exposure and tissue accumulation, mitigating their harmful effects to support a better neurodevelopmental outcome in children.

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13. Ringold SM, Cermak SA, Labus JS, Mayer EA, Aziz-Zadeh L. Sensory Over-Responsivity in Autism: A Bidirectional Brain-Gut-Microbiome Model. J Autism Dev Disord. 2026.

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14. Schuck RK, Ferguson EF, Spackman EK, Jevtic E, Millan ME, Paszek K, Komaki H, Ma Q, Phillips JM, Uljarević M, Gengoux GW, Hardan AY. Child Quality of Life as an Outcome Following Pivotal Response Treatment: Findings From Four Randomized Controlled Trials With Autistic Children. J Autism Dev Disord. 2026.

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15. Soriano V, Ramos JM, Gallego L, Mestre-Bach G, González-Fraile E, López-Ibor MI, Chiclana-Actis C, Faraco M, Pinargote H, Corpas M, Corral O, Blasco-Fontecilla H. Hospitalizations in adolescents with autism spectrum disorder are rising in Spain. Child Adolesc Psychiatry Ment Health. 2026.

BACKGROUND: Autism spectrum disorder (ASD) is a leading mental condition among adolescents globally and is associated with premature mortality. The analysis of hospitalization rates and trends in youth with ASD could be important for guiding earlier diagnosis and prompt interventions. METHODS: We retrospectively analyzed all hospitalizations in children and adolescents aged 11-18 years with ASD in Spain. The Spanish National Registry of Hospital Discharges was examined, spanning 2000 to 2021. RESULTS: During the 22-year study period, there were 2,015,589 hospitalizations among adolescents in Spain, of which 118,609 (5.9%) involved mental disorders. ASD was reported in 6,659 admissions, representing 5.6% of hospitalizations among youth with mental health disorders. Boys comprise 74.4%. Median age was 14 years old. Admissions with ASD experienced a 74-fold increase during the study period (p < 0.001). The in-hospital mortality rate for youth with ASD was 0.33%. Adolescents with ASD, as compared to those with other psychiatric conditions, had a higher rate of comorbid mental health disorders. However, intellectual disability was more frequent in youth with ASD than in the rest. Admissions of adolescents with ASD slightly declined during the first year of the COVID-19 pandemic but resumed their rising trend thereafter. CONCLUSION: Hospitalizations in adolescents with ASD have significantly increased in Spain during the last two decades. Boys represent nearly three-quarters of admissions.

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16. Tasu C, Oppetit A, Galbert C, Ouaki S, Zammouri I, Gazzano O, Mourao J, Mignot C, Cohen D, Benarous X. Major clinical improvement in a boy with developmental disabilities and a PTPN4 mutation with intensive re-education and an enriched environment in a day care hospital: a case report. J Med Case Rep. 2026.

BACKGROUND: Protein tyrosine phosphatase, non-receptor type 4 (PTPN4) is a gene involved in glutamate downstream signaling contributing to cerebral maturation. Loss-of-function of this gene has been reported in patients showing various neurodevelopmental disorders, although the PTPN4 gene is not clearly considered a disease-causing gene in the Online Mendelian Inheritance in Man catalogue. CASE PRESENTATION: Here, we report the case of a 7-year-old white boy with a homogeneous, heterozygous, 170 kb chromosomal deletion encompassing several exons of the PTPN4 gene. The mutation was transmitted by his father, who had an undiagnosed communication disorder. The patient was referred to a day care unit for complex neurodevelopmental disorders and a suspicion of autism spectrum disorder. He had a severe communication disorder associated with sensory integration issues, anxiety, and elimination disorder. During his 4 years in the day care hospital, he received educational, creative, and academic group activities and specific re-education. Group activities help generalize the newly acquired developmental skills by providing social reinforcers and opportunities for positive peer interactions. In turn, achieving social activities positively influences the patient’s self-esteem, emotional insight, and motivation to make new progress. CONCLUSION: Despite a severe communication disorder associated with sensory integration issues, anxiety, and elimination disorder, a diagnosis of autism spectrum disorder was ruled out, and remarkable progress was observed, which allowed our patient to attend same-age mainstream schools with personalized support at discharge. This case illustrates the effect of dimensional interventions to limit developmental impairments in a context of PTPN4 mutation and the benefit of providing an enriched environment in combination with individual re-education to improve developmental outcomes.

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17. Tirumala HP, Wang L, Li Y, Bajikar SS, Anderson AG, Wang W, Trostle AJ, Zahabiyon M, Bajic A, Kim JJ, Chen H, Liu Z, Zoghbi HY. Modulating alternative splicing of MECP2 is a potential therapeutic strategy for Rett syndrome. Sci Transl Med. 2026; 18(839): eadq4529.

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2), which encodes a transcriptional regulator essential for maintenance of normal neuronal function. The current US Food and Drug Administration-approved treatment for RTT, trofinetide, mildly alleviates some symptoms. In contrast, reintroducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique to e2), leading to production of only e1 mRNA, and showed that this up-regulated MeCP2 by 50 to 60% in mice. Next, we investigated the consequences of isoform switching in two independent RTT induced pluripotent stem cell (iPSC)-derived neuron models harboring mutations that reduce both MeCP2 expression and function. Exon 2 deletion in neurons derived from patients with MeCP2-G118E up-regulated MeCP2, ameliorated morphological and electrophysiological changes, and corrected the dysregulated transcriptome in these neurons. Isoform switching in neurons derived from patients with MeCP2-G118E, modeling a severe RTT mutation, only modestly affected MeCP2 protein abundance and, despite this, led to a partial transcriptomic rescue. Last, an exon 2-skipping morpholino up-regulated MeCP2-E1 in vivo in mice. These data set the stage for a potential therapeutic strategy using antisense oligonucleotides to promote isoform switching in patients with RTT who carry partially functioning alleles of MECP2.

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18. Verdugo-Díaz L, Martínez-Guerrero A, García-García DC, Avedaño-Estrada A, Ávila-Rodríguez M, Garzón-Cortés D, Martínez-Marcial M, Canuto-Ramírez V, Roldán-Roldán G, Ibarra-Coronado E. [(18)F]FDG metabolic brain network in C58/J strain: an autism murine model. Brain Struct Funct. 2026; 231(3).

Autism spectrum disorder (ASD) is associated with atypical brain network organization. Functional connectivity has been extensively studied using fMRI, which often reports reduced long-range connectivity alongside local hyperconnectivity. However, BOLD-based connectivity reflects neurovascular coupling and therefore provides an indirect estimate of neuronal activity. Complementary information may be obtained from [(18)F]FDG microPET, which quantifies regional glucose uptake—an index of synaptic energy demand integrated over minutes—although FDG-derived network organization has been scarcely examined in ASD. Here, “metabolic connectivity” refers to between-subject covariance in regional [(18)F]FDG uptake (group-level metabolic covariance networks), not within-subject temporal coupling as in BOLD-fMRI functional connectivity. We tested whether the C58/J mouse strain—an ASD-relevant model with social deficits and repetitive behaviors—recapitulates ASD-relevant metabolic network-level alterations. Using [(18)F]FDG microPET, we constructed ROI-wise metabolic covariance networks by correlating uptake values across animals and compared C58/J mice with C57BL/6 controls. The C58/J network exhibited higher clustering and a more locally cohesive organization than the C57BL/6 network. Nodal degree/edge density was reduced in the olfactory bulb, hippocampus, and hypothalamus. In contrast, the motor-related regions—including the striatum, brainstem, and superior and inferior colliculi—showed a higher degree/denser covariance. These findings suggest that C58/J mice display FDG-derived metabolic covariance network features qualitatively consistent with those reported in ASD FDG-PET studies, supporting this strain as a tool to investigate ASD-relevant pathophysiological mechanisms and to evaluate candidate interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00429-026-03087-8.

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19. Xu H, Shi Z, Guo X, Deng S, Wu M, Chen B, Qin J, Xu N, Zhao T, Chang Y, Song X. Low-Dose Sevoflurane Restores Prefrontal Excitatory/Inhibitory Balance and Improves Autism-Like Social Behavior: A Preclinical and Pilot Clinical Study. Drug Des Devel Ther. 2026; 20: 534484.

BACKGROUND: Medications aimed at modulating excitatory/inhibitory (E/I) balance have shown promise in alleviating the behavioral manifestations of autism spectrum disorder (ASD). We therefore aimed to investigate the potential of low-concentration sevoflurane, a GABA(A) agonist, to modulate E/I balance and affect autism-like behavior deficit in BTBR mice and ASD patients. METHODS: In the preclinical study, BTBR mice were exposed to 1% sevoflurane for 30 minutes daily, 5 days per week, from postnatal weeks 4 to 6. Behavioral and electrophysiological assessments were performed. In the clinical trial, ASD patients received 1% sevoflurane treatments for 2 hours per session, 3-5 times during the first two weeks, followed by 2-3 sessions per week for a total of 12 weeks. Assessments were conducted at baseline and the 14(th) week. The primary outcomes were evaluated using the Childhood Autism Rating Scale (CARS) and Clinical Global Impressions-Improvement (CGI-I) scale, while secondary outcomes were assessed using the Autism Diagnostic Observation Schedule-2 (ADOS-2), Clinical Global Impression-Severity Scale (CGI-S), Autism Treatment Evaluation Checklist (ATEC), and Autism Behavior Checklist (ABC). RESULTS: Our preclinical results demonstrated that repeated exposure to low-concentration sevoflurane restored E/I balance and improved social interaction and social memory without affecting repetitive behaviors. Accordingly, an open-label and single-arm clinical trial enrolled 20 ASD patients in Guangzhou Women and Children’s Medical Center. Significant reduction in CARS score of 4.7 points was observed between baseline and the end of treatment, which is both statistically and clinically significant. Additionally, 61% of ASD children demonstrated a positive response as measured by the CGI-I scale. Furthermore, analysis of secondary outcomes revealed that sevoflurane treatment primarily improved social impairments in ASD patients. Importantly, no significant safety concerns were observed during the one-year follow-up. CONCLUSION: Low-concentration sevoflurane shows promise as a novel therapeutic strategy for improving social deficits in ASD by modulating E/I balance. TRIAL REGISTRATION: Chinese Clinical trial Number: ChiCTR1900027459.

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20. Yum YN, Lau KW, Poon KY, Ho FC. Music therapy for social skills in children with autism spectrum disorder and intellectual disability: abridged secondary publication. Hong Kong Med J. 2026; 32 Suppl 1(1): 43-5.

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