Search Results (4,115)

Background/Objectives: Early autism screening needs to be both accurate and privacy-preserving, but single-source assessments can miss clinically important context. We therefore study a preliminary integrated framework that combines privacy-preserving questionnaire-based risk estimation with a second reasoning component based on a large language model (LLM) that evaluates symptom narratives. The objective is to test whether structured screening outputs can be translated into uncertainty-aware narrative reasoning within one privacy-conscious workflow. Methods: The proposed pipeline links a PATE-style AQ-10 screening stage to a MedPrompt-style consensus reasoning stage that operates on behavioral summaries and transcript-style inputs. Evaluation includes component-wise testing on AQ-10 data, an end-to-end controlled setting, synthetic stress testing, and transcript-only analysis on 26 examples. Results: In component-wise evaluation, the combined pipeline reaches ceiling performance on a controlled AQ-10 split, synthetic stress testing reduces accuracy to 97.2%, and transcript-only testing shows that contextual factors such as age substantially improve sensitivity. Conclusions: These findings support only a highly preliminary proof-of-concept under constrained evaluation conditions and should be interpreted as motivation for broader external validation rather than as evidence of practical decision-support readiness across settings. Full article

Access to autism intervention services is shaped by persistent structural constraints, including limited availability, cost, and service continuity, which often require caregivers to assume expanded roles in supporting their children’s development. This study examines how such constraints contribute to the emergence and persistence of caregivers as proxy interventionists and how technology-mediated systems support or partially support these roles from a human factors perspective. A sequential mixed-methods design was employed across two phases. The first phase integrated quantitative caregiver and service provider surveys with qualitative interviews to examine service access, early technology adoption, and satisfaction patterns during periods of disrupted service delivery. The second phase examined post-adoption contexts through caregiver and service provider qualitative interviews to understand sustained caregiver-mediated practices, technology use, and associated cognitive, emotional, and coordination demands. An empirically grounded conceptual framework was derived to organize relationships among structural access constraints, role redistribution, technology-mediated interaction mechanisms, and human factors demands. The findings highlight the need for human-centered digital systems that provide structured guidance, coordination support, and accessible intervention resources. This work contributes to the design of scalable, technology-mediated support systems for autism care and offers practical implications for user-centered digital health interventions. Full article

Background: Multi-center resting-state functional magnetic resonance imaging (rs-fMRI) is important for neurodevelopmental disorder diagnosis, but cross-site differences in repetition time (TR) can cause temporal feature misalignment. In addition, blood-oxygen-level-dependent (BOLD) signals are non-stationary, so disease-related information may be distributed across multiple time scales. Existing methods usually do not explicitly model physical sampling intervals or coordinate temporal and spectral information across scales, which may limit cross-site generalization in heterogeneous multi-center settings. Methods: We propose Spec-RWKV, a spectrum-guided linear recurrent framework for multi-site rs-fMRI diagnosis. It includes three components: PrismTimeMix, which models temporal dynamics using decay rates derived from physical half-lives and converts them adaptively across TRs; a TR-adaptive continuous wavelet transform, which aligns spectral representations across sites by adjusting frequency coverage; and spectrum-guided adaptive temporal aggregation, which uses spectral context to weight temporal features. Results: On ABIDE-I and ADHD-200, Spec-RWKV achieved AUCs of 75.86% and 76.31%, respectively. Under leave-one-site-out validation, it achieved the best mean AUC on ABIDE-I and the best mean accuracy and AUC on ADHD-200. Conclusions: Spec-RWKV explicitly models sampling-rate differences and multi-scale spectral structure, with results supporting strong cross-site generalizability. Full article

Background/Objectives: Congenital heart defects (CHDs) are the most common congenital anomalies, and survival into adolescence and adulthood now exceeds 90%. Increasing evidence suggests that children and adolescents with CHD face elevated risks of psychological, psychiatric and neurodevelopmental disorders. This systematic review aims to synthesize recent evidence on mental health outcomes, cognitive profiles, quality of life and associated risk factors in pediatric CHD. Methods: This review was conducted according to PRISMA 2020 guidelines. Five databases (PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library) were searched for studies published between January 2015 and November 2025. Eligible studies (observational, interventional and neuroimaging) included participants aged 0–18 years with any type of CHD and reported psychological, psychiatric, neurodevelopmental, cognitive or health-related quality-of-life outcomes. Due to substantial heterogeneity, findings were synthesized narratively. Results: Sixty-one studies involving over 120,000 participants were included. Children and adolescents with CHD showed increased prevalence of anxiety, depression, attention-deficit/hyperactivity disorder, autism spectrum disorder and post-traumatic stress symptoms compared with peers without CHD. Neurodevelopmental impairments, particularly in executive functioning, attention and memory, were frequently reported, especially in complex CHD and single-ventricle physiology. Health-related quality of life was consistently reduced, mainly in emotional and social domains. Parental mental health, disease severity and cumulative medical burden were significant correlates. Neuroimaging studies identified structural and functional brain alterations associated with cognitive and emotional vulnerability. Conclusions: Pediatric CHD is associated with substantial psychological and neurodevelopmental burden, particularly in complex disease. Early identification and integration of routine psychological care within multidisciplinary CHD programs are essential to improve long-term outcomes. Full article

When people interact, their actions reflect mood, attitude, and intention. Stern termed the affective qualities conveyed by actions, such as gentleness or rudeness, Vitality Forms (VFs). Previous research shows that children with autism spectrum disorder (ASD) differ from neurotypical (NT) peers in both perceiving and expressing these fundamental aspects of communication. It remains unclear whether these differences arise from structural or connectivity alterations in brain regions involved in VF processing. This study investigated structural and microstructural brain differences between children with ASD and NT peers, focusing on the VF-related network, which includes the dorso-central insula (DCI), premotor cortex (PM), middle cingulate cortex (MCC), and dorsolateral prefrontal cortex (DLPFC). Structural MRI data were collected from 60 right-handed boys aged 6–10 years (30 ASD, 30 NT), with diffusion MRI data available for a subset (20 ASD, 20 NT). A multimodal approach combined voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and probabilistic tractography. VBM revealed increased grey-matter volume in the PM, DLPFC, and MCC in the ASD group, with no differences in the DCI. TBSS showed white-matter microstructural alterations in premotor-related pathways. Probabilistic tractography further indicated atypical organization of tracts connecting the PM with the DLPFC, MCC, and DCI in children with ASD. Overall, the findings suggest atypical development of the premotor cortex and its associated white-matter connections in ASD, supporting theoretical accounts that link this network to altered processing of affective action dynamics during social interaction. Full article

As modern society grows increasingly complex, access to essential services such as healthcare, legal aid, tailored education, and psychological support remains heavily gated by socio-economic, neurological, and systemic barriers. This paper explores the transformative potential of Large Language Models (LLMs) and Generative Artificial Intelligence not merely as industrial productivity enhancers, but as vital “social scaffolds” capable of fostering a more inclusive society. Crucially, we propose a paradigm shift in the concept of Ethical Computing—moving from a passive defensive framework of non-maleficence (“do no harm”) to an active mandate of beneficence, where AI systems are explicitly developed to serve marginalized and un(der)served populations. Through this expanded ethical lens, we systematically analyze the democratizing impact of AI across four primary axes of inclusivity: socio-economic (providing zero-cost medical triage and legal translation for undocumented populations), neurospicy (acting as a non-judgmental communicative bridge for individuals with Autism Spectrum Disorder), pedagogical (delivering hyper-personalized executive function support for Special Educational Needs), and psychological (serving as an accessible, first-level triage system for mental health crises). By framing LLMs as a modern social safety net, we outline a clear trajectory for future research, advocating for an “ethical-by-design” development paradigm that explicitly prioritizes equity, accessibility, and the active dismantling of historical barriers for the digitally and socially disenfranchised. Full article

Mathematical abilities are critical for the developmental outcomes of children with autism spectrum disorder (ASD). However, little is known about these abilities and their association with the approximate number system (ANS) in preschoolers with ASD beyond Western samples, including Chinese children. This cross-sectional study examined whether formal and informal mathematical abilities differed between children with and without ASD and assessed the extent to which these abilities were associated with ANS acuity. Participants included 47 children with ASD and 47 typically developing (TD) children aged 3–7 years. All children were assessed on measures of formal and informal mathematical abilities, ANS acuity, and non-verbal IQ. No significant group differences in mathematical abilities were found among children aged 3–5 years. However, among children aged 6–7 years, the ASD group showed significantly lower performance in mathematical abilities compared to their TD peers. ANS acuity was significantly correlated with both formal and informal mathematical abilities in the ASD group, but only with informal mathematical abilities in the TD group. Furthermore, ANS acuity accounted for 5.4% of the unique variance in formal mathematical abilities specifically within the ASD group. The patterns of mathematical abilities and their relationship with ANS acuity differ between preschoolers with and without ASD. These findings suggest a differential association between ANS and formal mathematics learning in children with ASD, highlighting implications for the design of early numeracy interventions. Full article

Background: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition for which non-pharmacological interventions remain the primary therapeutic approach. Although research output in this field has increased substantially, a comprehensive synthesis of its developmental trajectory and emerging directions is still lacking. Methods: We conducted a bibliometric analysis of publications on non-pharmacological interventions for ASD indexed in the Web of Science Core Collection between 2001 and 2025. Knowledge structures, research hotspots, and temporal trends were visualized and analyzed using CiteSpace. Results: The field has transitioned from an early focus on behavioral interventions in children to a diversified and interdisciplinary research ecosystem spanning the lifespan. Recent growth has been driven by the integration of neuroscience-based approaches, particularly neuromodulation techniques, alongside continued refinement of behavioral, sensorimotor, and complementary therapies. Increasing attention has been paid to individual heterogeneity, methodological rigor, and mechanism-oriented research. Current frontiers emphasize multimodal intervention strategies, neural plasticity-based mechanisms, and the development of personalized precision intervention frameworks. Conclusions: This bibliometric analysis delineates the intellectual evolution of non-pharmacological intervention research for ASD and identifies key research gaps, particularly the need for longitudinal and pragmatic studies targeting individualized treatment response. The findings provide an evidence-informed overview of current concepts and emerging research directions in non-pharmacological care for ASD, with important implications for future clinical research, intervention design, and strategic research planning. Full article

Background: Cognitive and psychiatric disorders are caused by a complex interplay between genetic predisposition, environmental exposures, and dynamic molecular regulation in the brain. Animal models provide a controlled environment for examining these mechanisms, and advances in transcriptome and epigenomic technologies have greatly expanded our knowledge of disease-relevant pathways. Objective: This scoping review systematically maps and synthesizes the epigenetic and transcriptomic findings from the established animal models of four neuropsychiatric conditions—autism spectrum disorder (ASD), schizophrenia, depression, and Rett syndrome—drawing on a PRISMA-ScR-guided literature search. The review characterizes the breadth of evidence, identifies convergent and divergent molecular pathways, and highlights the translational gaps and therapeutic implications. Methods: Research employing chromatin accessibility testing, genome-wide DNA methylation mapping, single-cell and bulk RNA sequencing, histone modification profiling, and multi-omics integration in mouse and other validated animal models was thoroughly reviewed. A quality appraisal of the primary experimental studies (n = 63) was performed using a modified CAMARADES checklist. Results: Beyond generalized cellular stress responses, multi-omics analysis emphasizes the cell-type- and context-dependent nature of epigenetic changes in animal models, including isoform-specific histone modifications and model-dependent binding of HDAC/MeCP2 complexes to genes involved in synaptic plasticity. Single-cell RNA sequencing analyses have uniformly shown transcriptional changes in parvalbumin-positive (PV+) interneurons. Conclusions: The specific convergence of epigenetic disruptions in neural circuits involved in synaptic structure and inhibitory function could play a role in the generation of neuropsychiatric phenotypes in animal models, highlighting the importance of circuit- and cell-type-specific epigenetics while pointing to potential therapeutic avenues. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition increasingly associated with dysregulated neuroimmune signaling and altered neurotrophic homeostasis. Tumor necrosis factor-alpha (TNF-α) has been implicated in ASD pathophysiology; however, the downstream effects of TNF-α blockade on cytokine–neurotrophin interactions during neurodevelopment remain insufficiently characterized. In this study, we evaluated the effects of infliximab (IFX), a monoclonal anti-TNF-α antibody, on behavioral performance, neuroinflammatory cytokine profiles, glial activation, and brain-derived neurotrophic factor (BDNF) signaling in a propionic acid (PPA)-induced experimental ASD rat model. Methods: Experimental ASD was induced by propionic acid administration in rats. Animals were divided into control and treatment groups. Behavioral performance was assessed using the Morris Water Maze, direct social interaction, and three-chamber sociability tests. Levels of TNF-α, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and BDNF were measured in serum, hippocampal, and cerebellar tissues. Microglial and astrocytic activation were evaluated using CD11 and GFAP immunohistochemistry. Results: PPA administration resulted in pronounced impairments in learning, memory, and social behaviors, accompanied by elevated proinflammatory cytokine levels, increased BDNF expression, and marked glial activation in the hippocampus and cerebellum. Although IFX treatment significantly reduced TNF-α levels in central tissues, it did not improve behavioral deficits and was associated with persistently elevated IL-1β and IL-6 levels, sustained glial reactivity, and further alterations in BDNF levels. Conclusions: These findings suggest that TNF-α suppression alone does not normalize the disrupted cytokine–neurotrophin axis and may differentially modulate BDNF-related neuroplastic signaling during development. In conclusion, this study indicates that non-selective TNF-α blockade during neurodevelopment fails to confer behavioral benefit in experimental ASD and highlights the importance of considering cytokine–BDNF pathway interactions when designing immunomodulatory strategies for neurodevelopmental disorders. Full article

Background: Occupational therapists often provide sensory integration therapy (SIT) as part of interventions for children with autism spectrum disorder (ASD). However, evidence supporting its effectiveness remains limited. Therefore, this study aimed to explore the potential benefits of once-weekly SIT for children with ASD and co-occurring intellectual disability. Methods: A non-blinded single-group pre–post study was conducted using SIT once a week for 8 weeks. Participants were children aged 2–6 years who had been diagnosed with ASD, had a developmental index score of ≤70, and were classified as having severe autism according to the Childhood Autism Rating Scale. Outcome measures included the Goal Attainment Scaling (GAS), Vineland Adaptive Behavior Scales, Second Edition (VABS-II), Short Sensory Profile (SSP), and Parenting Stress Index, Short Form (PSI-SF). Data were analyzed using the Wilcoxon signed-rank test to compare pre- and post-intervention results. Results: Ten children completed the full intervention protocol. Changes were observed in some domains of the GAS and VABS-II; however, these findings were characterized by substantial uncertainty and considerable variability across participants. In contrast, no apparent changes were observed in the SSP or PSI-SF. Conclusions: The findings of this study do not support the effectiveness of sensory integration therapy (SIT) and should not be interpreted as evidence of intervention-related benefit. Rather, the results should be considered as exploratory observations obtained under real-world clinical conditions. Future research employing more rigorous designs, including the use of control groups, larger sample sizes, and blinded assessments, is required. Full article

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by heterogeneous behavioral symptoms and systemic comorbidities, including immune and gastrointestinal dysfunctions. Emerging studies suggest that glycosylation—a fundamental post-translational modification regulating cellular communication and immune responses—may play a role in ASD pathophysiology, yet its contribution remains underexplored. Methods: In this study, we developed an integrative transcriptomic and network analysis framework to investigate glycosylation-related gene expression changes and their functional associations in ASD. Using publicly available datasets from bulk and single-cell RNA sequencing of brain and blood tissues, we focused on four prior-knowledge gene subsets: glycogenes, extracellular matrix glycoproteins, immune response genes, and autism risk genes. Results: Differential expression and pathway enrichment analyses revealed consistent dysregulation of glycosylation pathways, including mucin-type O-glycan biosynthesis, glycosaminoglycan metabolism, GPI-anchor formation, and sialylation, across ASD tissues. These transcriptional changes were functionally linked to altered immune signaling (e.g., IL-17, Toll-like receptor, and complement pathways) and synaptic development pathways, forming a distinct glyco-immune axis. Network analysis identified key glycogenes such as GALNT10, NEU1, LMAN2L, and CHST1 as central molecular nodes, interacting with immune and neuronal regulators. Linkage disequilibrium analysis further revealed ASD-associated SNPs influencing the expression of these glycogenes in both blood and brain tissues. Conclusions: Together, these findings support a model in which disrupted glycosylation contributes to ASD pathophysiology by mediating immune dysregulation and altered neuronal connectivity. This study offers a systems-level framework to understand the molecular complexity of ASD and highlights glycogenes as potential biomarkers and targets for future therapeutic exploration. Full article

Neurological and mental disorders are among the main causes of disability worldwide, affecting over three billion people and increasing the socioeconomic burden. Advances in molecular genetics and genome engineering have led to gene-targeted therapies that address root causes rather than just symptoms. This review covers current genome-editing tools, including CRISPR/Cas, base editing, and prime editing. The focus is on the benefits of gene editing in the central nervous system, where post-mitotic neurons allow lasting effects after a single treatment. It also discusses emerging delivery platforms such as viral vectors, nanoparticles, and exosome systems, as well as methods to bypass the blood–brain barrier. Recent clinical progress in spinal muscular atrophy, Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease is highlighted, with promising preclinical results for autism, bipolar disorder, epilepsy, and other neurogenetic conditions. The review concludes with regulatory issues, market trends, and ongoing clinical trials, underscoring the potential of gene therapies to transform disease management and provide long-term solutions. Full article

Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model at postnatal day 7. We found that maternal inflammation induced significant methylation differences in neonates relative to control samples in both MIA and IS-HIE samples with no significant differences identified between the MIA and IS-HIE groups. MIA samples showed hypermethylation at loci involving craniofacial development and transcription factors important for regulating neurodevelopment and immune function. MIA samples also demonstrated significant hypermethylation at multiple mitochondrial genome CpGs. These findings suggest that maternal inflammation induces epigenetic alterations in fetal brain immune cells that are detectable in neonates. These changes may contribute to heightened neurodevelopmental risk in offspring following hypoxic injury, highlighting potential molecular pathways for future therapeutic targeting. Full article

Autism Spectrum Disorder (ASD) is a lifelong condition marked by challenges in social communication and repetitive behaviors. Current treatments, primarily behavioral therapies, often fail to address the core symptoms. Recent research has explored the potential of psychedelics, such as LSD, psilocybin, and MDMA, as a new therapeutic approach. While these substances primarily modulate the serotonin 5-HT_2A receptor, their therapeutic effects also involve interactions with other serotonergic, dopaminergic, and glutamatergic pathways, collectively promoting neuroplasticity—the brain’s ability to change and adapt. The specific receptors’ activation leads to structural and functional changes in the brain that can enhance social behavior and emotional regulation. Studies show that psychedelics may reduce symptoms of conditions like treatment-resistant depression and PTSD, highlighting their therapeutic potential. For ASD specifically, psychedelics may improve psychological flexibility, reduce distress, and enhance social interaction. While promising, the use of these substances requires careful consideration. Psychedelics can induce intense experiences and altered states of consciousness, necessitating strict monitoring and support during therapy. Ethical guidelines, including informed consent, are crucial, especially for vulnerable populations. In conclusion, psychedelics hold significant promise for treating ASD and other psychiatric disorders by promoting neuroplasticity and modulating complex signaling pathways. Continued research and clinical trials, conducted with strong ethical oversight, are essential to realizing their full therapeutic potential. Full article