Search Results (515)

The rodent prenatal valproate (VPA) treatment is a widely used animal model of idiopathic autism spectrum disorder (ASD). However, the presence of autistic-like symptoms is highly variable in treated offspring. The disruption of the excitation–inhibition balance of certain brain areas has been proposed as a main feature in both human ASD and the VPA model. The current study presents a detailed analysis of neural development, diverse behaviors, and neocortical excitability in a high number of individually identified VPA-treated rat offspring of both sexes. Neocortical excitability was assessed using electrophysiological and intrinsic optical imaging methods. Prenatal VPA treatment caused a delay in early postnatal sensorimotor development in rat pups of both sexes. Behavioral effects were associated with congenital morphological alterations (e.g., tail kink), as shown by stratification by principal component analysis and correlation analysis. Social deficits were evident only in the VPA-treated male offspring, while the females appear to be resistant to this effect. Prenatal VPA treatment was associated with sex- and region-dependent alterations in the excitability and seizure susceptibility of entorhinal and prefrontal cortical slices. Cortical excitability measures showed partial correlation with morphological and behavioral parameters. Thus, the current study further supports the validity of the rodent prenatal VPA model as a model of ASD for both sexes, but the variable degree of affectedness should be taken into account. Congenital malformation severity, including tail kink, may serve as a readily observable marker for subsequent physiological alterations, particularly in males. Full article

Background/Objectives: In both typical and atypical development, there is growing evidence that motor development sets the stage for development in other domains. This study aims to examine the feasibility of conducting cognitive and motor research-based tasks in a virtual reality (VR) environment with concurrent neuroimaging (functional near-infrared spectroscopy, or fNIRS) in autistic children. Methods: During a single study visit, participants will complete research-based tasks conducted in a virtual reality environment while wearing the fNIRS apparatus. Supplementary procedures will include a range of standardized assessments and questionnaires for caregivers and their children to complete. Anticipated Outcomes: These methods will yield a rich combination of data -- the kinematic data associated with performance during the research-based tasks, as well as the neural correlates underlying this performance. Conclusions: The overarching, long-term goal of this feasibility study is to explore the interrelationships between cognitive, motor, and social development in autistic children using a variety of research methodologies. A better understanding of these relationships and their neural correlates will inform future research, assessment methods, and intervention strategies across the autism spectrum. Full article

Background: Social interaction requires the efficient extraction and integration of visual information. Although atypicalities in global processing and visual perception have been reported in autism, their relationship with self-reported social-skills-related autistic traits remains unclear. Methods: Using an extreme-groups design, 179 university students completed the Autism-Spectrum Quotient (AQ). Individuals with scores at least ±1 SD were selected to form high-AQ (n = 20) and low-AQ (n = 22) groups. Participants completed two complementary psychophysical tasks assessing object perception under increasing visual noise and global–local visual processing. Results: The high-AQ group showed reduced recognition under high visual noise and slower responses under the global-incongruent condition. In the exploratory regression, visual-noise accuracy explained significant variance when entered alone, whereas global-incongruent Navon performance explained incremental variance and was the only significant unique contributor in the final model (R² = 0.280). Conclusions: These findings suggest that, within the selected extreme-AQ sample, AQ Social Skills scores are associated with complementary visual mechanisms responsible for extracting relevant information from noisy environments and integrating spatially distributed visual information into coherent global representations. These behavioural findings are consistent with a possible link between visual processing and self-reported social traits and with theoretical models proposing a role for magnocellular-dependent dorsal visual computations in social perception, although these neural mechanisms were not directly assessed. Full article

Severe mental illness (SMI) includes neuropsychiatric disorders of adult onset, but also those that begin to show symptoms in adolescence and early childhood. This review treats the psychotic spectrum disorders and autism as neurodevelopmental in origin, each arising from perturbation of early brain development rather than from a process beginning at the age of clinical presentation. Grouping them is a claim about developmental origin and not about shared pathogenesis: they differ in the nature and timing of the perturbation and in the cortical systems being organized when it occurs. The diversity of social, language, behavioral, and cognitive symptoms and traits observed within this class is now well recognized. The language adopted to recognize such diversity has employed the term “spectrum” (e.g., autism spectrum disorder (ASD) and schizophrenia or psychotic spectrum). The substantial expansion of structural and functional connectivity research over the past 40 years has shown that both ASD and psychotic spectrum disorders have also been conceptualized as disorders of brain circuitry. Moreover, and particularly for ASD, this research was developed within a diagnostic time frame that itself underwent six revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), from the third edition (DSM-III; 1980) to the fifth edition, text revision (DSM-5-TR; 2022), with the largest changes involving the elimination of the early language onset requirement and the consolidation of prior subtypes into a single autism spectrum disorder. The present review develops a mechanistic account of cerebral connectivity differences in autistic disorder as defined under DSM-III and DSM-IV, where diagnostic practice, and in particular the exclusion of clinically significant language delay from Asperger’s disorder, enriched cohorts for a subgroup in which cerebellar vermal lobule VI and VII abnormality, posterior callosal reduction, and atypical predictive processing were originally identified. The present account proposes, as a hypothesis rather than as an established finding, that deviation of vermal lobules VI and VII from typical development, in the direction of either hypoplasia or hyperplasia, both reported within the same DSM-III/IV cohort, and on evidence consistent with prenatal origin, initiates a developmental cascade that may shape postnatal cerebral connectivity through disinhibition of deep cerebellar nuclei and altered excitatory drive to thalamocortical circuits during sensitive periods. Cross-condition evidence indicates that vermal abnormality also occurs in conditions with distinct primary diagnoses (Joubert syndrome, fragile X, Rett syndrome, Williams syndrome, schizophrenia), producing the autistic-disorder cluster only when the upstream perturbation also affects cortical context-integration substrates at the relevant developmental window. These conditions are treated as further instances of a common neurodevelopmental class rather than as separate kinds of disorder, with autistic disorder as the focal case because it is where the vermal findings were first identified. Transdiagnostic connectivity evidence spanning autism and schizophrenia cohorts is examined to establish whether the cerebellar account generalizes across the SMI class or is specific to autistic disorder, and the regional and directional distribution of the cerebellar findings in each condition is treated as the discriminating variable. The framework proposes the cerebellum as a substrate for predictive internal models scaffolding auditory, social, and contextual learning, and is empirically testable through infant connectivity and event-related potential studies and through stratified re-analysis of multisite samples. Full article

Background: The prevalence of autism spectrum disorder (ASD) is increasing globally and in Saudi Arabia (SA), although many cases remain undiagnosed. Caregivers of children with ASD are confronted by challenges, especially mothers as primary caregivers, who have higher levels of stress and burden of care due to autism symptoms and difficulties of children, which negatively affects their quality of life (QoL). Objective: The primary outcome of this study was to assess primary caregivers’ quality of life and their perceptions of child-related difficulties associated with autism spectrum disorder (ASD) using the Quality of Life in Autism (QoLA) questionnaire. The secondary outcome was to examine the correlation between these two QoLA domains and identify the factors independently associated with each outcome Material and Methods: A convenience sample (247) of Saudi primary caregivers, primarily mothers, was taken from autism primary schools in Tabuk, Riyadh, Qassim, Hail, Jazan & Najran cities in SA by distributing an online questionnaire, which was composed of three parts, was used for data collection; Part I included demographic and clinical data of primary caregivers. Part II: The child’s personal characteristics. Part III: QoLA Questionnaire that measures the crucial aspects of living with autistic children and is composed of two parts (A and B). Data analysis was performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA), version 23. Results: More than half of the caregivers (50.2%) had a moderate level of QoL. Regarding caregivers’ perceptions of child-related difficulties, 70.9% reported high levels of difficulties, and 7.2% reported low difficulties. Quality of life was significantly associated with maternal age, educational level, number of children. The study’s univariate regression and multivariate regression analysis revealed that, QoL score had a significant negative association with maternal ages, university school and secondary school, working, and those who had medical diseases. In contrast, QoL level had a significant positive association with mothers who received training, had another person helped in caring for the child and who had enough income. Conclusions: Mothers of autistic children had poorer QOL and perceived more difficulties in caring for their children. Thus, educating sessions for mothers about dealing with their autistic children, psychological and financial support services are needed, which in turn improve their QoL. Full article

Objective: The objective of this study was to analyze the clinical phenotypes and genetic variant characteristics of four unrelated Chinese children carrying pathogenic variants in the CTCF gene and to explore the genotype–phenotype heterogeneity of autosomal dominant intellectual disability type 21 (MRD21, OMIM 615,502). Methods: Four pediatric patients admitted to Beijing Children’s Hospital, Capital Medical University, from 2020 to 2024 were enrolled in this retrospective study. All patients underwent medical history collection, physical examination, laboratory tests and high-throughput sequencing. Identified variants were verified in the probands and parents via Sanger sequencing or CNV-seq. Results: Four distinct heterozygous CTCF variants were identified: a missense variant c.1117C>T (p.His373Tyr); an 8.92 Mb microdeletion at 16q21-q22.1 (arr[GRCh37] 16q21q22.1(58,986,875–67,907,636)×1), encompassing the entire CTCF gene; a frameshift deletion c.615_618delGAAA (p.Lys206Profs*15); and an intragenic deletion of exons 8–10. Parental testing confirmed that all identified variants were of de novo origin. The missense variant and the frameshift deletion have been reported previously in ClinVar (VCV000521287.19 and VCV001308122.2), but the two deletions were not found in public databases. Three patients presented with global developmental delay consistent with MRD21, with variable additional features including autistic-like behavior and facial dysmorphism. Notably, two of these patients showed somatic overgrowth with height and weight above the 97th percentile, contrasting with the short stature classically emphasized in MRD21. The fourth patient was a preterm infant with neonatal chylothorax, cardiopulmonary failure, and multiple congenital cardiovascular malformations; developmental assessment at a corrected age of 11 months showed only mild lags. Conclusions: This study expands the spectrum of pathogenic CTCF variants in the Chinese population and underscores the marked phenotypic heterogeneity of CTCF-related disorders, ranging from benign developmental outcomes with complete catch-up to severe neonatal multisystem involvement. In neonates presenting with unexplained chylothorax and multisystem abnormalities, especially when accompanied by features suggestive of a neurodevelopmental syndrome, CTCF should be considered in the differential diagnosis. Given this heterogeneity, a broad genomic approach rather than targeted CTCF screening is recommended in patients with complex presentations. Full article

Autism is a prevalent neurodevelopmental disability among children in the United States. Enhanced Milieu Teaching (EMT) en Español Para Autismo is a caregiver-implemented language-focused naturalistic developmental behavioral intervention specifically for young children on the autism spectrum whose families are Latino and Spanish-speaking. The current study tested a reduced intensity adaptation of EMT en Español Para Autismo using a single-case experimental design study with four caregiver–child dyads. All children demonstrated characteristics of autism and lived in low-income Spanish-speaking households. Caregivers were taught to use EMT en Español Para Autismo strategies during play with their child using a cyclical teach–model–coach–review approach. Home visits occurred once each week. Three out of four dyads completed the study. None of the caregivers demonstrated functional relations between the cyclical teach–model–coach–review approach and their use of strategies; however, caregivers did increase their use of contingent language models and time delays when intervention began. Caregiver impressions of the intervention were positive, but they varied in their perceptions of some of the strategies (e.g., limiting instructions), consistent with participants in prior studies. Overall, the reduced intensity of the intervention and long gaps between visits may have limited the effectiveness of this intervention compared to findings in prior studies. More research is needed to tailor language interventions for Latino Spanish-speaking families with autistic children, especially those with limited resources. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits, and excessive repetitive behaviors. While ASD has a strong genetic basis, growing evidence suggests that epileptic seizures may serve as environmental risk factors for ASD development. The high comorbidity between epilepsy and ASD (20–30%) suggests potential shared neurobiological mechanisms, yet the causal relationship remains poorly understood. To investigate the causal role of seizures in the development of ASD-like pathology, we exposed adolescent mice (3 weeks old) to electroconvulsive seizures (ECS) for 10 consecutive days. This repeated ECS exposure led to the emergence of autistic-like behaviors including significantly decreased sociability, increased repetitive self-grooming, enhanced marble burying behavior, and anxiety-like behaviors, without affecting general locomotor activity. Additionally, repeated exposure to ECS induced significant changes in glutamatergic neurotransmission in the mice’s prefrontal cortex and hippocampus, brain regions critically involved in social cognition and behavioral regulation. Interestingly, these changes occurred without alterations in other excitatory/inhibitory neuronal markers, suggesting a specific impact on glutamate receptor expression rather than a general disruption of excitatory/inhibitory balance. These findings suggest that repeated seizures may contribute to ASD-like symptoms by specifically affecting key glutamatergic neurotransmitter systems, providing insights into the neurobiological mechanisms underlying the comorbidity between epilepsy and autism. In addition, repeated ECS differentially regulated histone deacetylase (HDAC) transcripts in a region-specific manner and produced seizure-intensity-dependent transcriptomic signatures. Full article

Autism spectrum disorder (hereafter autism) is increasingly recognised as being underdiagnosed in females worldwide, contributing to inequalities in clinical visibility and access to appropriate care. The clinical visibility of autism in females is influenced by diagnostic practices historically developed using predominantly male samples, which may be less sensitive to less overt or more socially camouflaged presentations. Greater levels of autistic camouflaging, including masking, compensations, and assimilation, have been proposed as one factor contributing to differences in the presentation of autism between males and females. However, camouflaging is resource-intensive, associated with significant psychological costs, and varies across contexts. Because camouflaging relies on cognitive–emotional resources, it may also fluctuate under conditions that influence these resources, such as the menstrual cycle. To date, no empirical research has directly investigated this relationship. This opinion article proposes the conceptual hypothesis that menstrual cycle-related fluctuations may influence the cognitive–emotional resources required for autistic camouflaging, with potential implications for clinical visibility, diagnostic recognition, mental health, and equitable access to care. By synthesising indirect evidence from autism, camouflaging, and menstrual health research, this conceptual framework aims to guide future empirical investigation and highlights the urgent need to better understand this overlooked intersection to improve diagnostic equity, clinical recognition, and women’s health outcomes globally. Full article

Background/Objectives: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to evaluate whether ASD and neurodegenerative disorders represent distinct entities or are linked through shared mechanisms operating across the lifespan. Methods: This narrative review synthesizes findings from genetic, molecular, cellular, circuit-level, and epidemiological studies examining ASD and major neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis. Emphasis is placed on identifying convergent pathways and evaluating evidence within a lifespan-oriented framework. Results: Across multiple levels of analysis, ASD and neurodegenerative diseases share partially overlapping biological mechanisms, including mitochondrial dysfunction, impaired proteostasis, neuroimmune alterations, and network-level instability. Genetic and molecular data reveal pleiotropic pathways influencing both early neurodevelopment and later neuronal resilience. Circuit-level studies highlight shared principles of network vulnerability, including cerebellar involvement and excitation–inhibition imbalance. Epidemiological data further indicate increased risk of dementia and parkinsonian features in autistic adults. These convergences suggest that early neurodevelopmental alterations may establish latent vulnerabilities that, under specific conditions, intersect with neurodegenerative processes later in life. Conclusions: ASD and neurodegenerative diseases are best understood as distinct clinical conditions that share partially overlapping biological substrates. Rather than implying a deterministic progression, the evidence supports a model of lifespan convergence in which timing, context, and individual susceptibility shape outcomes. This framework highlights the need for integrated research and clinical approaches that consider brain health as a continuous process from development through aging. 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

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

Background and Objectives: Williams syndrome (WS) is a rare neurodevelopmental genetic condition traditionally described as being associated with a highly sociable behavioral profile. However, growing evidence indicates that this characterization may oversimplify the socio-cognitive phenotype, as some individuals with WS exhibit socio-communicative and pragmatic difficulties that may overlap with ASD-related features, although these difficulties should not be interpreted as autism-specific. The present systematic review aimed to investigate the presence of autistic traits in WS, to synthesize evidence on pragmatic and socio-communicative difficulties, and to explore their association with adaptive functioning and, indirectly, adaptive and functional outcomes. Materials and Methods: This study follows a systematic search and selection process in accordance with PRISMA 2020 guidelines and employs a systematic review with structured narrative synthesis. A systematic search of PubMed, Scopus, and Web of Science was performed up to December 2022, supplemented by grey literature sources. Nine studies met the predefined inclusion criteria. Due to substantial methodological heterogeneity, findings were synthesized using a structured narrative approach. Study quality was evaluated using adapted criteria addressing research design, sample characteristics, measurement tools, and risk of bias. Results: The findings suggest that autistic traits may constitute a potentially clinically relevant, though not universal, aspect of the WS phenotype. Pragmatic language difficulties were consistently reported, particularly in relation to conversational management, social reciprocity, and context-appropriate language use. These difficulties appear to function as a key mechanism linking socio-cognitive characteristics with functional outcomes. Patterns of adaptive functioning showed both distinctions from and overlaps with autism spectrum disorder (ASD), especially in communication domains. Available genetic and molecular evidence points to a possible contribution of additional modifying factors for phenotypic variability, with possible phenotypic overlap between WS and ASD, particularly in pragmatic language and adaptive communication. Conclusions: The evidence supports a multidimensional and spectrum-based conceptualization of socio-communicative functioning in Williams syndrome. Despite strong social motivation, individuals with WS may experience meaningful pragmatic and adaptive challenges, with implications for assessment and intervention. These findings highlight the importance of multidimensional and individualized clinical approaches. Full article

Background/Objectives: Children with Autism Spectrum Disorder (ASD, here on termed autistic children) exhibit motor difficulties in social and non-social contexts. Although previous studies have reported behavioral and neural characteristics, their relationship remains largely unexplored. The current study aimed to investigate the behavioral and neural mechanisms underlying interpersonal synchrony in autistic children using simultaneous kinematic and Functional Near-Infrared Spectroscopy (fNIRS) recordings. Methods: Fifty-eight autistic or non-autistic children participated (mean age = 10.1, standard error = 0.3). fNIRS and an inertial measurement unit were used simultaneously to record the neural activity over frontotemporal and parietal regions and arm movement kinematics during a reach-to-clean-up task across three conditions: Watch—the child observed the tester clean up the blocks; Do—the child cleaned up the blocks independently; and Together—the child and tester cleaned up the blocks synchronously. Results: Behaviorally, autistic children demonstrated longer movement displacement, higher average velocity and acceleration, and a greater number of movement units. In terms of cortical activation, autistic children showed hypoactivation in the bilateral precentral gyrus and right inferior parietal lobe, along with hyperactivation in the right middle frontal gyrus, left inferior frontal gyrus, and left inferior parietal lobule. Correlations between kinematic and neural measures suggest that autistic children rely more on online/feedback control to compensate for reduced feedforward control. Conclusions: This study reveals unique compensatory strategies in autistic children, highlighting the connections between neural and behavioral characteristics. These findings have strong potential to inform the development of ASD screening tools and to guide targeted intervention strategies. Full article

Background: Neural stability, defined as trial-by-trial fluctuations in neural responses to the repetitive sensory input, is an indicator of neural processing stability. The auditory brainstem response (ABR) can provide an electrophysiological measure of neural stability. Findings on neural stability differences between autistic and neurotypical individuals are inconsistent, potentially due to methodological differences and sample heterogeneity. This study aimed to investigate the relationship between neural stability in the brainstem and autistic traits in a group of children with and without a diagnosis of autism. We examined whether the degree of neural stability differs based on the evoking stimulus and response component analyzed, and whether neural stability relates to parent-reported autistic traits, as measured by the Autism Spectrum Quotient (AQ) and social responsiveness scale-2 (SRS-2). Methods: In total, 41 participants had usable click ABRs and 34 had usable sABRs. Neural stability was quantified using Pearson correlation analyses between binaurally evoked subaverage ABR waveforms. Parent-reported measures of autistic traits were collected. Results: Neural stability differed across ABR components, with the click ABR being significantly more stable than sABR components. Decreased neural stability is significantly related to autistic traits measured by the AQ but not the SRS-2. There was no significant response component by AQ interaction. Conclusions: Neural stability in the auditory brainstem pathway is linked to individual differences in autistic traits measured by the AQ but not the SRS, implying that early sensory processing neural stability may be related to broader features of autistic traits rather than social communication alone. Full article