Search Results (344)

Background: Autism spectrum disorder (ASD) is associated with distinct visual attention patterns that provide insight into underlying social-cognitive mechanisms. Methods: This systematic review (PROSPERO: CRD42023429316), conducted per PRISMA guidelines, synthesizes evidence from 14 peer-reviewed studies using eye-tracking to compare oculomotor strategies in autistic children and typically developing (TD) controls. A comprehensive literature search was conducted in PubMed, Web of Science, and Science Direct up to March 2025. Study inclusion criteria focused on ASD versus TD group comparisons in individuals under 18 years, with key metrics, fixation duration and count, spatial distribution, saccadic parameters systematically extracted. Risk of bias was assessed using the QUADAS-2 tool, revealing high heterogeneity in both index tests and patient selection. Results: The results indicate that autistic children exhibit reduced fixation on socially salient stimuli, atypical saccadic behavior, and more variable spatial exploration compared to controls. Conclusions: These oculomotor differences suggest altered mechanisms of social attention and information processing in ASD. Findings suggest that eye-tracking can contribute valuable information about heterogeneous gaze profiles in ASD, providing preliminary insight that may inform future studies to develop more sensitive diagnostic tools. This review highlights visual attention patterns as promising indicators of neurocognitive functioning in ASD. Full article

Background and Objectives: Current evidence remains insufficient to determine whether the impact of autism spectrum disorder (ASD) on dental health is primarily mediated through oral hygiene and dietary habits or through direct effects of the disorder itself. This study examined the theoretical pathways through which ASD severity and toothbrushing-related and dietary-choice-related factors influence dental health in autistic children and adolescents. Materials and Methods: A cross-sectional study was conducted with 399 mothers reporting on their autistic children (aged 2–18 years, mean = 7.8). The exclusion criterion was being older than 18 years. Data included parent-reported data about ASD severity, dental health status, willingness to brush teeth, and dietary quality (assessed using the Diet Quality Inventory). Structural Equation Modeling (SEM) was used to analyze the direct and indirect effects of ASD severity on dental health, with probit regression coefficients estimated using the WLSMV method. Results: Parent-reported variables of ASD severity, diet quality, and toothbrushing willingness together explained 37% of the variance in dental health. The direct effect of ASD severity on dental health was 0.199 (p = 0.039). The indirect effect via toothbrushing was 0.137 (p = 0.006), and via diet quality, it was 0.070 (p = 0.020). The total indirect effect of ASD on dental health was 0.207 (p = 0.026), which was approximately as strong as the direct effect. The associations among the studied variables were statistically equivalent across sex and age groups. Conclusions: Parent-reported ASD severity shows significant association with dental health outcomes, both directly and indirectly, with toothbrushing behavior emerging as the primary mediator. Interventions that promote regular brushing (and, to a lesser extent, healthier eating) may help to reduce the dental health disparities associated with autism. Full article

Background/Objectives: Autism spectrum disorder is associated with executive functioning (EF) challenges, yet the neural correlates of EF challenges in autistic youth remain unclear. This study aimed to examine EF performance and cortical activation in autistic versus non-autistic youth, using functional near-infrared spectroscopy (fNIRS) during a modified Flanker task. Methods: Thirty age-matched (11.6 ± 0.8 years) autistic (N = 15) and non-autistic youth (N = 15) completed congruent and incongruent conditions of a modified Flanker task while cortical activation in prefrontal, parietal, and temporal regions was recorded using fNIRS. The Behavior Rating Inventory of Executive Function (BRIEF) was used to assess general EF impairments. Behavioral data (i.e., Flanker task mean reaction time/accuracy, and reaction time variability) and cortical activation were analyzed using ANCOVAs. Pearson correlations were used to determine the relationship between cortical activation, EF performance, and clinical measures. The significance level was set at p < 0.05, with FDR corrections for multiple comparisons. Results: While mean reaction time and accuracy were comparable across groups, autistic youth exhibited greater reaction time variability (autistic youth = 34.8 ± 10.36; controls = 26.4 ± 1.94, p = 0.02, Hedges’ g = 0.85) and higher BRIEF index scores compared to controls (p_s < 0.001, Hedges’ gs > 1.3; e.g., Global Executive Composite Score for autistic youth = 71.3 ± 3.7; controls = 47.8 ± 2.4), indicative of delayed EF development. During the incongruent condition, compared to non-autistic controls, autistic youth showed lower left inferior parietal lobe (IPL) activation (Mean HbO₂ in autistic youth = −0.02 ± 0.006 mmol.mm; controls = 0.01 ± 0.006 mmol.mm, p_s < 0.001, Hedges’ g = 0.5) and a lack of left-lateralized activation (e.g., left vs. right STS activation, p < 0.001, Hedges’ g = 0.41 in the non-autistic youth). In the ASD group, lower activation in the left STS was associated with lower EF performance (r = −0.28, p = 0.007), whereas greater activation in various right-hemispheric ROIs was associated with better EF performance (r = −0.31 to −0.35, p_s < 0.005), suggesting potential compensatory activation. Conclusions: The findings revealed ASD-specific differences in the neural correlates of EF performance and possible alternative compensatory activation patterns. These potential neural correlates of EF performance highlight the utility of fNIRS-based neural measures to better understand the neural bases of EF differences in autism. Study Registration: This study was approved by the Institutional Review Board (IRB) at the University of Delaware (Protocol #: 1947455) on 4 October 2022. Full article

Background/Objective: Neuroimmune and metabolic dysregulation have been increasingly implicated in the cognitive heterogeneity of autism spectrum disorder (ASD). However, it remains unclear whether anti-inflammatory diets engage distinct biological and cognitive pathways in autistic and neurotypical children. This study examined whether a 12-week anti-inflammatory dietary protocol produces group-specific neuroimmune–metabolic signatures and cognitive responses in autistic children, neurotypical children receiving the same diet, and untreated neurotypical controls. Methods: Twenty-two children (11 with ASD, six a on neurotypical diet [NT-diet], and five neurotypical controls [NT-control]) completed pre–post assessments of plasma IFN-γ, CXCL1, RANTES (CCL5), trimethylamine-N-oxide (TMAO), and an extensive ENI-2/WISC-IV neuropsychological battery. Linear mixed-effects models were used to test the Time × Group effects on biomarkers and cognitive domains, adjusting for age, sex, and baseline TMAO. Bayesian estimation quantified individual changes (posterior means, 95% credible intervals, and posterior probabilities). Immune–cognitive coupling was explored using Δ–Δ correlation matrices, network metrics (node strength, degree centrality), exploratory mediation models, and responder (≥0.5 SD domain improvement) versus non-responder analyses. Results: In ASD, the diet induced robust reductions in IFN-γ, RANTES, CXCL1, and TMAO, with decisive Bayesian evidence for IFN-γ and RANTES suppression (posterior P(δ < 0) > 0.99). These shifts were selectively associated with gains in verbal learning, semantic fluency, verbal reasoning, attention, and visuoconstructive abilities, whereas working memory and executive flexibility changes were heterogeneous, revealing executive vulnerability in individuals with smaller TMAO reductions. NT-diet children showed modest but consistent improvements in visuospatial processing, attention, and processing speed, with minimal biomarker changes; NT controls remained biologically and cognitively stable. Network analyses in ASD revealed a dense chemokine-anchored architecture with CXCL1 and RANTES as central hubs linking biomarker reductions to improvements in fluency, memory, attention, and executive flexibility. ΔTMAO predicted changes in executive flexibility only in ASD (explaining >50% of the variance), functioning as a metabolic node of executive susceptibility. Responders displayed larger coordinated decreases in all biomarkers and broader cognitive gains compared to non-responders. Conclusions: A structured anti-inflammatory diet elicits an ASD-specific, coordinated neuroimmune–metabolic response in which suppression of CXCL1 and RANTES and modulation of TMAO are tightly coupled with selective improvements in verbal, attentional, and executive domains. Neurotypical children exhibit modest metabolism-linked cognitive benefits and minimal immune modulation. These findings support a precision-nutrition framework in ASD, emphasizing baseline immunometabolic profiling and network-level biomarkers (CXCL1, RANTES, TMAO) to stratify responders and design combinatorial interventions targeting neuroimmune–metabolic pathways. Full article

Background: Feeding and eating disorders (FEDs) often present in comorbidity with other psychiatric conditions, with a growing body of evidence underscoring their association with autism spectrum disorder (ASD). Individuals with ASD or significant autistic traits (ATs), especially females, often engage in camouflaging strategies to mask their symptoms. However, empirical research on the role of camouflaging within this association is still emerging. This study aimed to assess the prevalence of ATs in individuals with FEDs and to examine their connection with psychological well-being, along with the role of camouflaging as a potential mediator in this association. Methods: A total of 131 individuals with FEDs were assessed through a medical record review, a socio-demographic form, and self-administered questionnaires evaluating FEDs symptoms (EDI-3) and ASD-related features (RAADS-R, AQ, EQ, CAT-Q). Results: In total, 16% of patients scored above the possible high ATs in clinical settings (whereas 53% exceeded the original cut-off) and 25% showed significant camouflaging, without differences between FED diagnoses. ATs were associated with both FED symptom severity and general maladjustment. Importantly, the latter was not directly explained by ATs themselves, but was mediated separately by camouflaging and FED symptomatology. After statistical adjustments, the parallel mediating pathways contributed similarly (48% and 52%). Conclusions: A considerable subset of individuals with FEDs presents significant ATs, with camouflaging arguably linked to psychological distress through a pathway parallel to that of FED symptomatology. This overlap between FEDs and ASD may be clinically meaningful, highlighting the potential importance of assessing ATs and camouflaging to support personalized diagnostic and therapeutic interventions. Full article

Background/Objectives: This study aims to compare adaptive and maladaptive behaviors of children with Autism Spectrum Disorder Level 1 (ASD-L1) and their experiences of bullying in comparison to a matched control group. Additionally, we explored which of such behaviors predicted both victimization and aggression in both samples. Methods: The sample consisted of 96 children and adolescents, 48 with ASD-L1 (31 Colombians and 17 Spanish) and 48 controls (31 Colombians and 17 Spanish), matched by age, gender, and socioeconomic status. Adaptive and maladaptive behaviors, as well as bullying experiences, were assessed. Results: Children with ASD-L1 reported higher levels of clinical and school maladjustment and lower levels of personal adjustment compared to the control group. Although no significant differences were found in bullying victimization, the ASD-L1 group showed higher aggression scores. In this group, lower personal adjustment predicted victimization, whereas higher clinical maladjustment predicted aggression. In contrast, in the control group, aggression was predicted by school maladjustment. Conclusions: Aggressive behavior in children with ASD-L1 was linked to higher levels of clinical maladjustment, while better personal adjustment served as a protective factor against bullying victimization. These findings emphasize distinct socio-emotional mechanisms underlying bullying involvement in autistic and typically developing youth. Full article

Background: Neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), intellectual disability (ID), and global developmental delay (GDD), frequently have underlying genetic causes. NCKAP1, a gene essential for actin cytoskeleton remodeling and neuronal development, has recently gained recognition as a promising candidate gene in NDDs. While not yet linked to a defined Mendelian disorder, damaging NCKAP1 variants have been identified in individuals with NDDs. NCKAP1 is also expressed in cardiac tissue, with emerging evidence supporting its potential involvement in cardiac development. Here, we present a case of a patient with neurodevelopmental delay and congenital heart disease (CHD) harboring a novel damaging NCKAP1 variant. Methods: Comprehensive clinical evaluations and trio exome sequencing (proband and parents) were conducted on a patient with complex cardiac and neurodevelopmental phenotypes. Results: We identified a de novo heterozygous frameshift variant in NCKAP1, NM_205842.3:c.2956_2959del p.(Ser986Hisfs*34), predicted to result in loss of function through nonsense-mediated mRNA decay. The patient’s clinical features included neonatally diagnosed and surgically repaired infradiaphragmatic total anomalous pulmonary venous return (TAPVR), intellectual disability, speech delay, and autistic traits. His NDD phenotypes and variant type align well with previously described NCKAP1-associated NDD, while the cardiac anomaly adds evidence to the gene’s expanding phenotypic spectrum. This represents the fourth reported case linking NCKAP1 variants to CHD and/or neurodevelopmental delay. Conclusions: This case strengthens the growing recognition of NCKAP1 in both neurodevelopment and cardiac formation. It highlights the importance of genetic testing for individuals with overlapping developmental and cardiac conditions. Further research is warranted to elucidate the role of NCKAP1 in cardiac development and its contribution to CHD. Full article

Background and Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficits, restricted interests, and repetitive behaviors. At present, there is no pharmacological intervention that reliably targets the core symptoms of ASD; instead, medications are primarily used to manage associated or concurrent symptoms such as irritability, aggression, anxiety, attention difficulties, and sleep disturbances. This review summarizes the current evidence for pharmacological treatments in ASD, emphasizing how these interventions are used in a symptom-focused, adjunctive manner, and highlighting efficacy, mechanisms, limitations, and emerging therapeutic targets. Methods: A comprehensive literature review was conducted across PubMed, Cochrane Library, and Embase to identify clinical trials, systematic reviews, meta-analyses, and preclinical studies on pharmacological interventions for ASD. Seventy-seven references were integrated to reflect the current state of evidence. Results: Established pharmacological strategies include atypical antipsychotics for severe irritability and aggression, as well as antidepressants, stimulants and non-stimulant agents, mood stabilizers, and anxiolytics for selected comorbid symptoms, although efficacy is often modest and variable, and side effects can be significant. Adjunctive and investigational approaches targeting glutamatergic and GABAergic neurotransmission, monoaminergic systems, and neuroinflammatory and oxidative stress pathways show preliminary promise but remain experimental. Across all categories, pharmacological treatments are most effective when embedded in individualized, multimodal care plans that integrate behavioral, rehabilitative, and psychological interventions. Conclusions: This review maps pharmacologic strategies in ASD onto their underlying neurobiological mechanisms and clarifies how evidence strength differs across drug classes and symptom domains. Ongoing advances in genetics, synaptic and circuit-level neuroscience, and neuroimmune signaling are expected to yield more specific, mechanism-based pharmacological approaches for autistic behaviors, with the potential to improve long-term functioning and quality of life when combined with comprehensive psychosocial care. Full article

Children with autism spectrum disorder (ASD) often display atypical emotional expressions and physiological responses, making emotion recognition challenging. This study proposes a multimodal recognition model employing a late fusion framework combining facial expression with physiological measures: electrodermal activity (EDA), temperature (TEMP), and heart rate (HR). Emotional states are annotated using two complementary schemes derived from a shared set of labels. Three annotators provide one categorical Ekman emotion for each timestamp. From these annotations, a majority-vote label identifies the dominant emotion, while a proportional distribution reflects the likelihood of each emotion based on the relative frequency of the annotators’ selections. Separate machine learning models are trained for each modality and for each annotation scheme, and their outputs are integrated through decision-level fusion. A distinct decision-level fusion model is constructed for each annotation scheme, ensuring that both the categorical and likelihood-based representations are optimally combined. The experiments on the EMBOA dataset, collected within the project “Affective loop in Socially Assistive Robotics as an intervention tool for children with autism”, show that the late fusion model achieves higher accuracy and robustness than unimodal baselines. The system attains an accuracy of 68% for categorical emotion classification and 78% under the likelihood-estimation scheme. The results obtained, although lower than those reported in other studies, suggest that further research into emotion recognition in autistic children using other fusions is warranted, even in the case of datasets with a significant number of missing values and low sample representation for certain emotions. Full article

Background: Autism spectrum disorder (ASD) and related neurodevelopmental conditions are a significant public health concern, with diagnostic delays hindering timely intervention. Traditional assessments often lead to waiting times exceeding a year. Advances in artificial intelligence (AI) and biomarker-based screening offer objective, efficient alternatives for early identification. Objective: This review synthesizes the latest evidence for AI-enabled technologies aimed at improving early ASD identification. Modalities covered include eye-tracking, acoustic analysis, video- and sensor-based behavioral screening, neuroimaging, molecular/genetic assays, electronic health record prediction, and home-based digital applications or apps. This manuscript critically evaluates their diagnostic accuracy, clinical feasibility, scalability, and implementation hurdles, while highlighting regulatory and ethical considerations. Findings: Across modalities, machine learning approaches demonstrate strong accuracy and specificity in ASD detection. Eye-tracking and voice-acoustic classifiers reliably differentiate for autistic children, while home-video analysis and Electronic Health Record (EHR)-based algorithms show promise for scalable screening. Multimodal integration significantly enhances predictive power. Several tools have received Food and Drug Administration clearance, signaling momentum for wider clinical deployment. Issues persist regarding equity, data privacy, algorithmic bias, and real-world performance. Conclusions: AI-enabled screeners and diagnostic aids have the potential to transform ASD detection and access to early intervention. Integrating these technologies into clinical workflows must safeguard equity, privacy, and clinician oversight. Ongoing longitudinal research and robust regulatory frameworks are essential to ensure these advances benefit diverse populations and deliver meaningful outcomes for children and families. Full article

Background: Pathogenic variants in the TRIP12 gene are associated with Clark-Baraitser syndrome, a condition characterized by neurodevelopmental disorders, including intellectual disability, autism spectrum disorder (ASD), and speech delay. Phenotypic expression is variable, and facial features are not consistently present. Familial inheritance is rare. Methods: Whole-exome sequencing (WES) was performed on a proband with speech disorder and ASD, as well as on her parents. Clinical assessment included developmental, cognitive, and physical evaluations. Results: A heterozygous missense variant c.3404A>T (p. Asp1135Val) in the TRIP12 gene was identified in both the proband and her father. Both presented with speech disorder and ASD without facial features or severe intellectual disability. Conclusions: In line with recent genotype–phenotype studies, missense TRIP12 variants tend to be associated with milder neurodevelopmental presentations, typically characterized by mild to moderate intellectual impairment, variable autistic traits, limited or absent facial features, and a low incidence of epilepsy. This familial case further presents the phenotypic spectrum of TRIP12 missense variants and highlights that ASD and speech disorder may occur as isolated neurodevelopmental findings without syndromic features. The report reinforces the relevance of TRIP12 analysis in the differential diagnosis of ASD and language disorders, even in individuals lacking physical traits, supporting more accurate genetic counseling and broader awareness of inherited TRIP12-related conditions. Full article

Background/Objectives: Autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social and communication differences, is complex and aetiologically heterogeneous. Untargeted metabolomics is emerging as a tool in screening for biochemical abnormalities. This research was conducted using the Australian Autism Biobank resource and involved analysis of plasma metabolites to characterise metabolite differences between autistic children and controls. Methods: We sought to identify molecular signatures in the plasma of study subjects using mass-spectrometry methods. We included 955 untargeted plasma metabolites from autistic children (n = 491; 2–18 years; 78% male) and control subjects (n = 97; 2–17 years of age; 51% male). Statistical analyses were performed using questionnaire data for both groups, including standardised scores from the Autism Diagnostic Observation Schedule—Second Edition (ADOS-2), which measures the severity of autism-related behaviours. We also evaluated intellectual disability by examining the relationships between metabolites and clinical phenotypes. Results: After controlling the false discovery rate at 5%, we identified significant negative associations between the uncharacterised metabolites X-21383 and X-24970 and ASD status (p = 1.85 × 10⁻⁶ and p = 1.92 × 10⁻⁵ respectively). X-21383 was also found to be significantly reduced in autistic children with coexisting intellectual disability when compared with controls (p = 6.06 × 10⁻⁶). No significant associations were identified between the metabolite data and ADOS-2 scores. However, greater levels of X-16938, N1-methyladenosine, and 2-oxoarginine were found to be suggestively associated with higher ADOS-2 scores (p = 2.95 × 10⁻⁴–9.6 × 10⁻⁵). Conclusion: This metabolomics study in the Australian Autism Biobank has identified several novel metabolites associated with core autism diagnostic behaviours. Full article

Structure of the study: Aims: The primary aim is to explore intergenerational clinical issues caused by the underdiagnosis of female autistic spectrum disorder (ASD) in mental illness (MI) patients by calculating the proportion of patients with mental health conditions who are autistic. Secondary aims are to derive further values for the true prevalence of female ASD and to derive a mathematical model to estimate the improved efficiency of management based on the correct diagnostic formulation. Context: Review diagnosis problems and background issues relating to female autism which affect the diagnosis and management of ASD and associated MIs. Methodology: An inductive process using Bayes’ theorem including a novel form akin to a medical test with secondary data from peer-reviewed sources, and the key variable of the unbiased value for the prevalence of ASD in females. Derivation of a model for management efficiency based on the Pareto Principle. Results: Prevalence values for ASD in various mental illnesses and conditions consequent on or associated with ASD and MI. Further data for the prevalence of female ASD with a range of 19 values. Estimation of the efficiency gains as advocacy for the revision of methods of treatment. Discussion: The centrality of diagnosing ASD in mothers with mental illness, in particular perinatal depression, to break a common intergenerational cycle. Problems to overcome and aspects of effective management including environmental and therapeutic interventions. Summary: This paper will, for the first time, calculate the proportions of children and young women with a mental illness (MI) who are autistic, and consider the consequences. Recent information suggests female autistic spectrum disorder (ASD) is much more common than previously thought, with a likely prevalence of 6% and with 80% undiagnosed at the age of 18. ASD then becomes a common comorbidity of female mental illness with nearly one in five women who develop a mental illness being autistic. ASD has heretofore been regarded as a pediatric condition and, though now thought to be lifelong, it is still not well recognized by adult health services. Most mental illness first presents in the teens and early twenties, although anxiety can begin even earlier. Comorbid ASD is more difficult to diagnose due to diagnostic overshadowing, and ASD comorbidity makes the mental illness more severe and more difficult to treat. The consequences of perinatal depression are particularly concerning due to their intergenerational effects. Recognized ASD is readily treatable with an approach empathetic to neurodiversity. Improving the transition from adolescence to young adulthood by increasing knowledge of autism in adult health services would dramatically improve female mental health at surprisingly little effort or extra cost. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits, repetitive behaviors, and restricted interests. Although its pathogenesis is not fully understood, emerging evidence suggests a connection between gut microbiota alterations and ASD. The role of specific bacterial species, particularly Enterococcus faecium, in the development of ASD remains unclear. This study aimed to investigate the impact of E. faecium derived from the feces of autistic children on mice. Thirty male BALB/c mice were divided into three groups: control, E. coli, and E. faecium treatment groups. E. faecium was administered orally for 30 days. Behavioral assessments, including open field tests, sucrose preference, Y-maze, and social interaction tests, were performed to evaluate anxiety, depression, memory, and social behavior. Additionally, serum 5-HT levels were measured, and colon and brain tissues were analyzed for inflammation, blood–brain barrier (BBB) integrity, and histological changes. Stool DNA sequencing was used to assess microbiota diversity and composition. Treatment with E. faecium significantly altered behavior in mice, including increased anxiety, depression, impaired memory, and social dysfunction. Colon histology revealed severe damage, including increased inflammation, reduced tight junction protein expression, and decreased mucin-2 levels. Elevated serum lipopolysaccharide (LPS) levels indicated systemic inflammation, and gut microbiota analysis showed significant dysbiosis. In the brain, particularly within the hippocampus and cortical regions, E. faecium induced neural damage, heightened inflammation, and compromised blood–brain barrier integrity. Enterococcus faecium from autistic patients can induce significant behavioral changes in mice, potentially via gut microbiota dysbiosis, intestinal barrier disruption, and brain inflammation. These findings suggest that E. faecium may contribute to gut–brain axis dysregulation in ASD, although further mechanistic studies are warranted. Full article