Search Results (3,343)

Background/Objectives: White–Sutton syndrome (WHSUS; OMIM 616364) is a rare neurodevelopmental disorder caused by pathogenic variants in the POGZ gene and characterized by developmental delay, intellectual disability, speech impairment, autism spectrum features, and dysmorphic traits. Although most reported cases are sporadic, inherited forms are exceptionally rare. We describe a familial case of WHSUS involving an affected mother and two children carrying a heterozygous POGZ nonsense variant, highlighting marked intra-familial phenotypic variability and expanding the clinical spectrum of the disorder. Methods: Clinical evaluation included multidisciplinary assessments. Genetic testing was performed using clinical exome sequencing (CES) with a virtual neurodevelopmental disorder (NDD) gene panel, followed by Sanger confirmation and segregation analysis in family members. The POGZ transcript reference NM_015100.3 was used for variant nomenclature and verified with the Mutalyzer tool. CNV detection from NGS data was performed using the Alissa CNV caller (Agilent) and visualized via IGV; the Xp11.22 microduplication was confirmed by chromosomal microarray (aCGH) and parental segregation analyses. Results: CES identified the heterozygous pathogenic POGZ variant c.1522C>T (p.Arg508*) in the female proband (III₆), an infant presenting with global developmental delay, hypotonia, speech impairment, gait abnormalities, and characteristic dysmorphic features. Segregation analysis demonstrated maternal inheritance and confirmed the presence of the variant in her affected brother (III₄), who also carries a de novo 1.79 kb microduplication at Xp11.22, while the maternal grandparents tested negative, indicating a de novo origin in the mother. The mother exhibited an attenuated phenotype, including mild neuropsychiatric and gastrointestinal manifestations. The variant is predicted to undergo nonsense-mediated decay (NMD), consistent with a moderate clinical presentation; however, experimental validation was not performed. Conclusions: This report documents a rare familial occurrence of WHSUS with highly variable expressivity. Our findings broaden the phenotypic and molecular characterization of POGZ-related disorders and emphasize the importance of comprehensive segregation studies and early genomic diagnosis. While experimental data link POGZ deficiency to DNA repair defects, no longitudinal clinical studies have demonstrated increased cancer risk in WHSUS; therefore, formal malignancy screening guidelines cannot be established at present, and this issue deserves future study in larger cohorts or registries. Full article

Copy number variants (CNVs) are genomic rearrangements that carry a substantial risk for neurodevelopmental and neuropsychiatric disorders. Among these, recurrent deletions and duplications at the 16p11.2 locus are robustly associated with autism spectrum disorders, schizophrenia, epilepsy, and related conditions, yet also display marked variability in penetrance and phenotypic expression. Accumulating evidence indicates that 16p11.2 gene dosage influences multiple stages of brain development, from early progenitor dynamics and neuronal migration to synaptic formation, refinement, and plasticity. However, how disruptions across these processes are integrated over time, and how they relate to the observed variability and incomplete penetrance, remains poorly understood. In this review, we summarize the current evidence on the impact of 16p11.2 CNVs on brain development, focusing on cellular and circuit-level processes that shape neural connectivity. We discuss how gene dosage imbalance influences early developmental trajectories, synaptic formation and pruning, interneuron maturation, and activity-dependent plasticity, and consider how these processes interact across developmental stages. We suggest a conceptual framework wherein 16p11.2 CNVs do not impose fixed pathogenic outcomes, but rather they contribute towards developmental constraints that shape the timing and stability of neural circuit development. Consequently, these constraints increase vulnerability to neurodevelopmental and psychiatric outcomes in a context-dependent manner. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted and repetitive behaviors, and sensory processing abnormalities, including food selectivity. Due to the lack of effective causal therapies, alternative approaches such as dietary interventions are increasingly being explored. This study aimed to assess the impact of dietary factors on the nutritional status of children with ASD. Methods: A total of 103 children (75 with ASD and 28 controls) were included. Nutritional status was assessed using biochemical markers and standardized anthropometric measurements. Associations between nutritional status and dietary factors, particularly elimination diets implemented either on medical indications or in the absence of clinical justification, were analyzed. Results: ASD diagnosis was independently associated with lower height SDS (Standard Deviation Score). Food selectivity was significantly associated with growth patterns: children with food selectivity showed a higher prevalence of short stature compared with the control group (15.2% vs. 0%, p = 0.033). Children following elimination diets had significantly lower BMI SDS compared with those without dietary restrictions (−0.35 [−1.29 to 0.05] vs. −0.22 [−0.78 to 1.14], p = 0.046), although only 11.1% had medical indications for such interventions. Among non-supplemented participants, vitamin D deficiency was significantly more prevalent in the ASD group (84.6% vs. 33.3%, p < 0.001). Conclusions: Elimination diets were the only dietary factor associated with a clinically relevant reduction in BMI SDS in children with ASD. Food selectivity alone was not associated with impaired nutritional status. Most elimination diets were implemented without confirmed medical indications. These findings highlight the importance of evidence-based dietary management and routine vitamin D supplementation in this population. Full article

Autism spectrum disorder is increasingly linked to altered microglial biology. However, current research models are limited by outdated descriptions of microglial “activation”. Here, we propose that microglial involvement in ASD is best understood as a problem of state mismatch, in which temporally programmed and regionally specialized microglial states fail to align with local developmental demands. We synthesize evidence across genetic models, human transcriptomics, and experimental systems to examine three axes of misalignment: developmental timing, circuit specificity, and functional phenotype. These mismatches produce divergent outcomes, including both excessive and insufficient synaptic pruning, and reflect a decoupling between microglial activation markers and effector capacity. We further evaluate molecular recognition systems governing microglia–synapse interactions, with emphasis on complement signaling and glycan-mediated pathways such as sialic acid–Siglec signaling and polysialylation. While glycosylation is not a universal driver of ASD pathology, it represents a plausible regulatory layer controlling synapse visibility and microglial engagement. This framework reconciles conflicting findings in the literature and positions microglia as dynamic developmental effectors whose misaligned state trajectories contribute to circuit-level dysfunction in ASD. Full article

While the cerebellar dopaminergic system is suggested to be implicated in neurodevelopmental disorders, especially autism spectrum disorder (ASD), the details of its disturbances remain unclear. We performed a comparative analysis of human (GTEx) and mouse (GSE144046, GSE144277) transcriptomes, complemented by RT-qPCR in DAT-KO rats, to identify dopaminergic gene associations in the normal cerebellum and neurodevelopmental disorder models. Pairwise dopaminergic gene correlations were generally weak, with a slight increase in interaction complexity in ASD models. However, weighted gene co-expression network analysis identified a robust gene module involving Comt, which was consistently associated with synaptic translation across mouse datasets. These associations reflect regulatory processes in the whole cerebellum, which is commonly represented in rodent studies but absent in human data, which are acquired in studies of cerebellar subregions. ASD modeling exerted contrasting effects: Cul3 haploinsufficiency increased the number of genes involved in the module with a decrease in connectivity, while Mbd5 haploinsufficiency led to module collapse. These findings confirm neurodevelopmental disorders as a heterogeneous condition where divergent backgrounds uniquely rewire cerebellar dopaminergic networks. Considering the cerebellum’s role in ASD and that some ASD medications target the dopamine system, further investigation of these identified trends may support the development of more personalized therapeutic approaches. Full article

Although exercise interventions have been shown to alleviate core symptoms of Autism Spectrum Disorder (ASD), the neural mechanisms underlying these improvements, particularly those involving the White Matter Network (WMN), remain poorly understood. This study investigated the effects of a Mini-Basketball Training Program (MBTP) on core symptoms and WMN in children with ASD. This study adopted a two-site cluster-Randomized Controlled Trial (cRCT) design. Participants from two special education centers in China were randomly assigned to either an intervention group (MBTP) or a control group (CON). The participants underwent a 12-week MBTP. Core symptom assessments and a Diffusion Tensor Imaging (DTI) scan were conducted before and after the intervention. The individual WMNs were constructed using Deterministic Fiber Tracking (DFT). Graph theoretical analysis was applied to examine changes in WMN topological properties after MBTP. The MBTP significantly improved core symptoms in children with ASD, alongside the decreased normalized clustering coefficient (Gamma, γ), characteristic path length (Lambda, λ), small-world attributes (Sigma, σ), and increased global efficiency (E_glob). The nodal clustering coefficient (NCC) increased in the left cuneus (CUN.L) and left cerebellum 9 (CRBL9.L). Notably, the increased NCC in CRBL9.L was significantly correlated with improvements in core symptoms following the MBTP. The improvement in core symptoms in children with ASD following exercise intervention is associated with the remodeling of the WMN, highlighting the cerebellum as a key node in this neural mechanism. Full article

The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson’s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation. Full article

The Active Music Programme (MAP) is an interdisciplinary initiative designed to foster inclusion, communication, and emotional well-being through participatory music-making. Integrating active music education, guided improvisation, and creative interaction, MAP seeks to enhance quality of life for individuals with diverse abilities. This pilot project, implemented in a special education centre with adolescents and adults with Autism Spectrum Disorder (ASD), combines weekly collaborative sessions led by music and education professionals. Using a qualitative, participatory framework, the study aims to examine how musical engagement is expected to support shared attention, emotional regulation, and social connection, positioning MAP as a replicable model for inclusive education and community practice. Full article

Internal state terms (ISTs) include words describing emotions, thoughts, volitions, obligations, desires, and perceptions. This scoping review aimed to map and synthesize evidence regarding the production of ISTs in individuals with Autism Spectrum Disorder (ASD) without intellectual disability and to investigate the effects of age, gender, Theory of Mind (ToM) skills, and elicitation tasks on their production. A literature search was conducted manually and electronically in Scopus, ScienceDirect, ERIC, and PubMed, identifying 29 peer-reviewed empirical studies published between 2006 and 2025. Findings were heterogeneous. Some studies reported lower IST production in individuals with ASD compared to neurotypical controls, whereas others found differences only in specific IST categories, mainly cognition and emotion terms, or reported no significant group differences. Findings regarding gender, ToM skills, and elicitation tasks were mixed. In both groups, older participants produced more ISTs than younger participants; however, developmental trajectories suggested that emotion and cognition terms were particularly challenging for individuals with ASD, who required more time to acquire them than their typically developing (TD) peers. Furthermore, TD participants produced significantly more ISTs when narrating people’s everyday interactions, whereas communication context did not appear to influence IST production in individuals with ASD. Research examining IST production in preschoolers and adults with ASD remains limited, and little is known about the developmental trajectories of ISTs in this population. Full article

Background/Objectives: Cochlear implantation (CI) represents a well-established intervention for the management of severe to profound sensorineural hearing loss. The co-occurrence of severe hearing loss and Autism Spectrum Disorder (ASD) presents unique diagnostic and therapeutic challenges that significantly impact post-implantation outcomes. This review aims to synthesize the current literature on cochlear implantation in children with Autism Spectrum Disorder (ASD), including diagnostic, audiological, rehabilitative, and functional outcome considerations. Methods: A structured search of PubMed and Scopus was performed for English-language articles published between January 2000 and January 2026, focusing on audiological assessment, rehabilitation challenges, multidisciplinary management, and post-implant functional outcomes in this population. Results: The findings synthesized in this review suggest that cochlear implantation in children with Autism Spectrum Disorder must be interpreted within a broader communicative-ecological framework rather than through auditory metrics alone. These findings highlight a multidimensional model of post-implant outcomes, shaped by the dynamic interplay between auditory access, social engagement, family context, and language-learning environments. Conclusions: Most children with ASD and severe-to-profound hearing loss show improvements in speech perception and production after cochlear implantation, although outcomes are highly variable. A multidisciplinary approach, through coordinated collaboration among specialists, enhances family engagement, optimizes compliance with care plans, and ultimately contributes to improved clinical and developmental outcomes. ASD should not be considered a contraindication for CI; however, careful individual assessment, realistic parental counseling, and a multidisciplinary approach availability to evaluation and rehabilitation are essential. Full article

Background/Objectives: Autistic traits are distributed dimensionally across psychiatric populations, yet their systematic assessment in mood and psychotic spectrum disorders remains limited. While elevated autistic traits have been documented in schizophrenia spectrum disorders, evidence in bipolar disorder (BD) and major depressive disorder (MDD) is scarce, and no studies have applied the clinician-rated PANSS Autism Severity Score (PAUSS) to mood disorder populations. This study aims to investigate the presence and severity of autistic traits across psychotic spectrum disorder (PSD), BD, and MDD in an outpatient sample using the PAUSS. Methods: In this cross-sectional naturalistic outpatient study, clinically stable adult patients with MDD, BD, or PSD, without autism spectrum disorder, were assessed with the Brief Psychiatric Rating Scale (BPRS) and PAUSS. Group comparisons, adjusted models, correlation analyses, principal component analysis, and multinomial logistic regression were performed. Results: A total of 165 patients were included (MDD, n = 84, BD, n = 45, PSD, n = 36). Compared with the mood disorder groups, PSD patients were younger and showed higher BPRS scores. PSD was also characterized by significantly higher PAUSS total, social, and communication scores, whereas PAUSS RRB did not differ in univariate analyses. In the overall sample, BPRS severity correlated positively with all PAUSS dimensions, while age showed only weak or non-significant associations. Diagnosis-stratified analyses revealed that the association between psychopathology and autistic traits was present in MDD and BD, but not in PSD. PCA showed that autistic trait dimensions converged on a broad common profile and differed across diagnostic groups, with PSD showing the most distinct pattern. In multinomial logistic regression, higher BPRS, higher PAUSS social and communication scores, and younger age independently distinguished PSD from MDD and BD; PAUSS RRB showed an inverse association only in the multivariable model. Conclusions: This study supports a transdiagnostic perspective on autistic traits in adult psychiatric populations, highlighting disorder-specific differences across diagnostic categories. Social and communication impairments emerged as key dimensions distinguishing PSD from mood disorders. Assessing autistic traits in psychiatric settings may improve diagnostic precision and inform personalized, stratified treatment approaches. Full article

Applied Behavior Analysis (ABA) is recognized as one of the most evidence-based interventions for students with autism spectrum disorder (ASD), although its effectiveness relies on consistent classroom implementation by teachers. This study investigated the extent to which teachers of students with ASD in Qatar implement ABA techniques and whether implementation levels vary by gender, educational level, school type, years of experience, and teaching stage. A descriptive–analytical design was utilized on a sample of 155 teachers from government and private schools. Data were collected using the Applied Behavior Analysis Implementation Scale for Teachers of Students with ASD in Qatar (ABAIS-Qatar), a 26-item instrument developed and validated for this study across five dimensions. Teachers reported a high overall level of ABA implementation (M = 4.10, SD = 0.48). The Behavior Identification and Goal Setting and Strategy Application and Intervention dimensions received the highest ratings, while the Motivation and Corrective Procedures dimensions were rated at a moderate level. A five-way MANOVA revealed significant multivariate differences across years of experience and teaching stage. Post hoc analyses indicated that teachers with more than 15 years of experience reported significantly higher implementation of motivational and corrective procedures than those with 6–10 years of experience and that primary-stage teachers demonstrated superior classroom behavior management compared to intermediate-stage teachers. The findings have implications for teacher professional development and ABA training in both inclusive and specialist educational settings in Qatar. Full article

Detailed attention and cognitive rigidity contribute to poorer social functioning and mental health. These cognitive functions can be measured using questionnaires or behavioral tasks but existing methods have limitations. The Detail and Flexibility Questionnaire (DFlex) addresses several of these limitations. This study developed a Japanese translation of the DFlex and collected valid evidence for its intended score interpretations. Sixty participants with autism spectrum disorder (ASD), 140 without ASD, and five participants who chose not to disclose whether they had an ASD diagnosis completed the Japanese version of the DFlex and the Japanese version of the Autism-Spectrum Quotient (AQ). Data from 192 participants were analyzed. Internal consistency was good as was the internal structure, except for one item. McDonald’s omega and Cronbach’s alpha demonstrated good internal consistency and item–total correlation was acceptable, except for one item. The Japanese DFlex correlated strongly with the AQ Attention to Detail and Attention Switching subscales, supporting convergent validity. Regarding known-group validity, the ASD and non-ASD groups showed significant differences on the Cognitive Rigidity and Attention to Detail subscales. Based on its reliability and internal structural validity, the Japanese DFlex provides a better understanding of ASD-related cognitive traits for both research and clinical practice. Full article

Background: Autism spectrum disorder (ASD) is associated with immune dysregulation in a subset of individuals, though findings remain heterogeneous and poorly defined, particularly regarding immune subtypes and metabolic context. Methods: We analyzed whole-blood microarray data from GSE18123 (GPL570: ASD n = 46, controls n = 19; GPL6244: ASD n = 68, controls n = 21) using an integrated immunometabolic framework. CD4⁺ T-cell transcriptional programs were used to assign dominant immune phenotypes (TH1, TH2, TH17, Tfh, FOXP3⁺ Treg, Tr1-like). Metabolic demand was quantified via the τ-axis; execution capacity was assessed using cytosolic and mitochondrial energy compensation ratios (CECR, MECR). Induction–execution mismatch was captured by three Gap metrics (Cytosolic, Warburg, Global). Functional validation correlated these metrics with transcriptional signatures of folate transport, one-carbon metabolism, receptor-mediated micronutrient uptake (LRP2–CUBN–AMN), cobalamin processing, and vitamin D activation across both platforms. Results: Six immunometabolic CD4⁺ subtypes were identified within ASD. τ-axis discrimination was strongest for Tr1-like (AUC = 0.811) and Tfh (AUC = 0.825) states, while TH17 profiles were indistinguishable from controls. Despite variation in metabolic demand, CECR and MECR remained relatively preserved, indicating decoupling between induction and execution capacity. Global Gap values were most negative in Tfh and TH1 states and positive in TH17 and controls. Negative Gap states showed coordinated suppression of ATP-intensive micronutrient acquisition pathways, including folate transport (FOLR1/2, SLC19A1), megalin–cubilin-mediated uptake (r ≈ 0.77–0.79), and vitamin D activation (CYP27B1). Intracellular cobalamin processing was upregulated in proportion to metabolic demand (r > 0.9). Findings were directionally replicated across both datasets. Conclusions: These data demonstrate that ASD exhibits structured immunometabolic heterogeneity characterized by subtype-specific demand–capacity imbalance. The Global Gap framework provides transcriptomic evidence of energetic deficit in Tfh- and Tr1-like-dominant states. Future clinical studies should incorporate subtype-stratified assessment of micronutrient status and metabolic execution capacity. Full article

Background: Children with autism spectrum disorder (ASD) commonly exhibit impairments in executive functioning, which can affect their cognitive and adaptive functioning. Play-based neurohabilitation approaches have been proposed as complementary strategies to stimulate frontal-executive processes. Objectives: The primary objective of this study was to assess the effectiveness of LEGO^®-Based Neurotherapy (LBN) in enhancing executive functioning in children with autism spectrum disorder (ASD). Methods: A pilot quasi-experimental pre-post intervention study was conducted in children with ASD. Children voluntarily enrolled either in a LBN program or in a non-intervention comparison group being control (CTRL) group. Executive functions were assessed at baseline and follow-up using the BANFE-3 battery. Results: Children participating in the LBN program showed greater improvements in dorsolateral executive-function scores and total executive-function indices compared with CTRL group. These findings suggest a potential association between participation in LBN and executive-function improvement. Conclusions: LBN may represent a promising complementary neurohabilitation approach for supporting executive functions in children with ASD. Full article