Autism Research

Background: Infant muscle tone reflects early central nervous system integrity and has been associated with later motor and cognitive development, including autism traits. The cerebellum regulates both motor control and higher-order socio-cognitive functions and has been repeatedly implicated in autism, but its role in linking infant muscle tone to adolescent autistic traits has not previously been studied in a large, prospective population cohort. Methods: We used data from the prospective Generation R Study. Infant muscle tone (hypotonia and hypertonia) was assessed via Prechtl examination, and third-trimester fetal transcerebellar diameter was measured using ultrasound n=6,842). Cerebellar morphology at ages 6, 10, and 14 years (n=4,861) was measured using structural MRI. Linear mixed-effects models tested associations between infant muscle tone and 35 anatomical and 10 functional cerebellar regions. Causal mediation models tested whether cerebellar volume mediated associations between infant muscle tone and adolescent autistic traits at age 14 (Social Responsiveness Scale). Results: Hypotonia predicted larger vermis IX volumes across childhood (beta=0.037, pFDR =0.043). Hypertonia showed an age-dependent association with left lateral lobule IX (beta=-0.0027, pFDR =0.041), with differences diminishing with age. Third-trimester transcerebellar diameter did not predict postnatal muscle tone. Given its significant main effect, vermis IX volume was tested as a mediator, but did not mediate the pathway to adolescent autistic traits. However, infant hypotonia showed a small direct association with elevated autistic traits at age 14, specific to girls (beta=0.0255, p=0.020). Conclusions: Infant muscle tone is associated with localized differences in cerebellar volumes. These associations are specific to vermal and left hemispheric lobule IX, a region commonly implicated in spinocerebellar postural control, axial stability, and higher-order sensorimotor integration. Furthermore, infant muscle tone was not predicted by prenatal cerebellar diameter, and cerebellar volumes did not mediate the association between infant hypotonia and adolescent autistic traits in our study. Future research should further investigate these findings in clinical populations, integrating longitudinal whole-brain, multi-modal imaging to clarify the association between infant muscle tone, the cerebellar functioning, and autistic traits.

The Autism Spectrum Quotient (AQ-50) is widely used to assess autistic traits, yet its Hungarian version has not been psychometrically evaluated. We assessed the reliability, factor structure, temporal stability, convergent validity, and clinical utility of the Hungarian AQ-50 and a revised translation (AQ-50-HU-R) in two samples (N1 = 1967; N2 = 423), including autistic and non-autistic participants. The AQ-50-HU-R showed high internal consistency and test-retest reliability. A bifactor model provided the best fit ({chi}2[1125] = 1650.433, p < 0.001; CFI = 0.991; TLI = 0.990; RMSEA = 0.033 [90% CI = 0.030-0.037]; SRMR = 0.083), with 71% of common variance attributable to a general autistic traits factor. The total score distinguished clinically verified autistic participants from participants reporting no ASD diagnosis (AUC = 0.906), with a cutoff of 25. Associations with ADOS scores were weak or nonsignificant. The AQ-50-HU-R is best interpreted as a reliable total-score screening measure, supporting referral for comprehensive autism assessment.

In many high-income countries, autistic children attend preschools ranging from exclusive special education (SE) to inclusive mainstream education (ME). These settings differ in staff expertise, capacity to implement structured autism interventions, exposure to typically developing peers, and cost. In this prospective longitudinal study, we compared 119 autistic children across three preschool settings in southern Israel: SE with TABAM services, an extended intervention program; SE without TABAM; and ME. Children completed behavioral assessments at the beginning and end of their first preschool year, yielding measures of cognition, autism symptom severity, joint attention, verbal abilities, adaptive behaviors, and aberrant behaviors. Developmental trajectories varied across children, with some demonstrating marked gains and others showing limited progress. On average, developmental changes were modest across most domains and were not explained by educational setting. The only exception was verbal ability, where children in SE with TABAM showed greater gains than children in SE without TABAM. These findings suggest that autistic children in ME and SE demonstrated broadly similar developmental trajectories during their first preschool year. Further large-scale research is needed to identify which children may benefit more from specific educational environments and intervention approaches, and to inform ongoing efforts to optimize preschool services for autistic children.

Background The global increase in autism spectrum disorder (ASD) diagnoses is expected to substantially increase demand for long-term rehabilitation services. However, little is known about how this increase affects rehabilitation service utilization and capacity in low- and middle-income countries. Methods We conducted a retrospective longitudinal study of children receiving developmental care at a tertiary rehabilitation center in Salvador, Brazil (2017-2026). Patients were classified into Childhood Autism, Other ASD, and non-ASD diagnostic groups according to ICD-10 diagnoses. Temporal trends in admissions and patients under follow-up were analyzed using generalized additive models and segmented Poisson regression. Factors associated with follow-up duration were evaluated using multivariable Cox proportional hazards models. Results Among 2,123 eligible children, 833 (39.2%) had Childhood Autism, 462 (21.8%) had Other ASD, and 828 (39.0%) had non-ASD diagnoses. Compared with children with non-ASD diagnoses, those with Childhood Autism entered care at younger ages, were predominantly male (77.9% vs. 57.2%), attended more visits, and remained under follow-up longer (all P<0.001). Admissions of children with Childhood Autism increased by 30.2% annually before 2023 but declined thereafter (-19.6% annually; P<0.001). Despite this decline, the number of children with Childhood Autism receiving ongoing rehabilitation continued to increase, reflecting prolonged follow-up. In adjusted analyses, Childhood Autism was associated with a substantially lower hazard of reaching the last recorded follow-up visit than non-ASD diagnoses (adjusted hazard ratio, 0.35; 95% CI, 0.30-0.40; P<0.001). Conclusions The rapid increase in ASD admissions fundamentally reshaped rehabilitation service utilization. Because children with ASD remained under follow-up substantially longer than those with other developmental conditions, they accounted for an increasing share of the rehabilitation caseload, even after new admissions began to decline. These findings highlight the importance of planning rehabilitation services according to both new admissions and the cumulative demand generated by long-term follow-up.

Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by a microdeletion within chromosome 22q13.3 1-6, and accounts for [~]1-3% of cases of autism spectrum disorders (ASD). Individuals with PMS typically present with neonatal hypotonia, severe speech delay, intellectual disability, motor impairments, and autism-related features, although additional manifestations such as epilepsy, sleep disturbances, and developmental regression are common. As in ASD, there is considerable heterogeneity in cognitive and behavioral impairments in PMS, making it difficult to determine which features arise directly from SHANK3/Shank3 deficiency and how deficits manifest across development. In the present study, we transferred the targeted Shank3 mutation, previously characterized on the Sprague Dawley background, onto the Long-Evans strain and performed a longitudinal behavioral assessment of Shank3-deficient rats from infancy to adulthood. The rats were evaluated for delays in early sensory and motor development, and ultrasonic vocalizations as neonates, social behavior, short term memory and gait as juveniles, and cognitive-executive dysfunction using a touchscreen-based visual discrimination and reversal learning task as adults. Despite profound reductions and/or complete loss of Shank3 protein expression, heterozygous and homozygous male and female rats showed normal physical and neurological reflexes across development, yet female Shank3 knockout pups showed a selective reduction in distress-associated ultrasonic vocalizations. As juveniles, subtle abnormalities emerged in short-term memory and limb coordination, while social preference for novelty and recognition was normal. Prominent behavioral abnormalities were observed in adults characterized by rapid and error-prone responding to visual stimuli during discrimination learning and reversal. These data suggest that rats with complete or partial Shank3 deficiency produce a selective behavioral profile in which high-order cognitive dysfunction is more pronounced than deficits in basic sensorimotor or select social behaviors. More broadly, these findings highlight executive dysfunction as a key consequence of the loss of Shank3. For the first time, we report the loss of Shank3 expression on a Long-Evans background strain as a valuable translational tool for investigating cognitive dysfunction and therapeutic windows in Shank3-associated disorders.

Background: Altered gamma-aminobutyric acid (GABA) neurotransmission is a proposed mechanism underlying autism spectrum disorder (ASD), prompting evaluation of several GABA-modulating pharmacotherapies. However, it remains unclear whether these interventions improve ASD broadly or preferentially affect specific symptom domains. Methods: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials evaluating GABA-modulating pharmacotherapies in individuals with ASD. PubMed/MEDLINE, Embase, Scopus, and CENTRAL were searched from inception to April 1, 2026. Outcomes were prespecified as global autism severity, social communication, functional communication, restricted and repetitive behaviours (RRBs), adaptive behaviour, and irritability. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results: Thirteen randomized controlled trials evaluating three GABA-modulating interventions (bumetanide, arbaclofen, and valproate) were included. GABA-modulating therapies were associated with statistically significant improvements in global autism severity (Hedges' g = -0.25, 95% CI -0.46 to -0.03; p = 0.028) and adaptive behaviour (Hedges' g = -0.09, 95% CI -0.15 to -0.02; p = 0.023). No significant pooled effects were observed for social communication (Hedges' g = -0.26, p = 0.077), functional communication (Hedges' g = -0.01, p = 0.869), RRBs (Hedges' g = -0.21, p = 0.126), or irritability (Hedges' g = -0.07, p = 0.543). After Holm-Bonferroni step down procedure, neither global autism severity nor adaptive behaviour remained statistically significant (Holm-adjusted p = .140 and .138, respectively). Adverse events were predominantly gastrointestinal, neurological, metabolic, and appetite-related. Overall risk of bias was variable, and the certainty of evidence ranged from very low to moderate. Conclusions: GABA-modulating pharmacotherapies did not demonstrate a robust, multiplicity-corrected benefit in any of the six prespecified ASD symptom domains. Nominal, unadjusted improvements in global autism severity and adaptive behaviour did not withstand correction for multiple comparisons and should be regarded as hypothesis-generating rather than confirmatory. Larger, adequately powered randomized trials using standardized domain-specific outcome measures are needed to determine whether individual GABA-modulating agents provide clinically meaningful benefit.

Background: Sleep problems are common in autism, emerge early in life and reduce quality of life, yet the mechanistic link between autism and poor sleep remains unclear. Human and rodent data indicate that difficulty falling asleep is a core feature of autistic insomnia, pointing to impaired responses to sleepiness as the underlying cause. We previously showed that adult mice carrying a mutation in the high-confidence autism gene Shank3 (Shank3{Delta}C) recapitulate this insomnia phenotype and struggle to respond to sleepiness after acute sleep deprivation. Here, we used Shank3{Delta}C mice to examine the molecular basis of sleepiness and how this autism-associated mutation alters it to inform understanding of sleep problems in autistic individuals. Methods: This study used RNA-sequencing and bioinformatics to identify molecular targets underlying the effect of the Shank3{Delta}C mutation on the molecular basis of sleepiness across development in male mice. We first compared cortical genome-wide gene expression following acute sleep deprivation and recovery sleep in adult wild-type (WT) and mutant mice. We then used polysomnography and RNA-sequencing to assess the response to increased sleepiness in WT and mutant mice at postnatal days 24 and 30. Results: The neurotypical response to acute sleep deprivation shifted from upregulating neuronal growth and development pathways at P24/P30 to upregulating DNA damage repair and neuronal activity-dependent transcription in adulthood. The Shank3{Delta}C mutation largely blocked recruitment of these pathways at P24 and in adulthood while paradoxically increasing the magnitude of the mutant response at P30. In addition, mutants consistently upregulated oxidative stress pathways linked to neurodegeneration and protein synthesis regardless of age, whereas WT animals downregulated these functions. Limitations: This study examined gene expression only in male mice, used a single autism rodent model, and averaged signals across mixed cortical cell types. Future work should include females, additional autism models, and single-cell approaches in additional brain regions to further characterize the cellular effects of sleep deprivation and autism-associated mutations. Conclusions: The Shank3{Delta}C mutation impairs the molecular accumulation of and response to sleepiness, both by elevating oxidative stress responses and by blocking the age-typical upregulation of pathways that differ between juveniles and adults.

Objectives To evaluate the positive and adverse effects of parent-mediated interventions (PMIs) versus care as usual for children with autism. Setting Systematic review and meta-analysis and Trial Sequential Analyses (TSA), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods We searched for randomised clinical trials of PMIs for children with autism in the databases CENTRAL, EMBASE, LILACS, PsycINFO, MEDLINE, and SCI-EXPANDED (up to 13 August, 2025), complemented with manual searches. 12,359 articles were screened. Data were synthesised using meta-analyses and Trial Sequential Analyses (TSA), and risks of bias and certainty of the evidence were evaluated. Primary and secondary outcome measures The primary outcome was autism characteristics. Secondary outcomes were adverse effects, child adaptive functioning, child language, child and parent quality of life, and parental stress. Ten exploratory outcomes were included. Results 32 trials (N=1,625) comparing PMIs to usual care, waiting list, or no intervention were included. All trials had a high risk of bias. The multiplicity-adjusted threshold for statistical significance was p = 0.013 due to the number of outcomes. Meta-analyses and TSAs showed it could be rejected that PMIs reduced autism characteristics (MD = -0.88; 95% confidence interval -2.92 to 1.15; p = 0.05, 4 trials, N=353, low certainty), child adaptive functioning (7 trials, N=408), child language (4 trials, N=308), or parental stress (7 trials, N=385). Due to insufficient data, the remaining secondary meta-analyses could not be conducted. Meta-analyses of exploratory outcomes showed beneficial effects concerning child behaviour problems and parent sensitivity/synchronicity. Conclusions This meta-analysis found no benefits of PMIs on child autism characteristics, child adaptive functioning, child language, or parental stress. Benefits were found in reduction of child behaviour problems and improved parent sensitivity/synchronicity. The evidence remains uncertain, and more trials including outcomes of adverse effects and quality of life are needed.

Empirical evidence from traditional inhibitory control tasks regarding inhibitory deficits in high autistic traits has been mixed, indicating that this issue remains controversial. Although sex differences are widely documented in autistic cognitive profiles, their role in inhibitory gating mechanisms remains underexplored. Given that the expression of inhibitory gating deficits may be modulated by the social versus non-social nature of stimuli, and no prior study has investigated this topic by integrating both sex differences and stimulus domain, we addressed these two questions with the attribute amnesia paradigm. We manipulated stimulus type (non-social vs. social). In Experiment 1, participants performed a location task with animal drawings as targets and were unexpectedly asked to report animal identity on a surprise trial. High autistic trait females showed significantly higher accuracy on the surprise trial than all other groups, reflecting a failure to actively filter out task-irrelevant non-social information, that is, a reduced inhibitory gating efficiency. In Experiment 2, using face stimuli and a self-vs. other-face design, this gating deficit was no longer expressed: all groups performed at chance levels on the identity judgment, regardless of autistic trait level, sex, or face type. This dissociation aligns with a dual-mechanism framework: the inhibitory gating deficit in high autistic trait females is specific to non-social stimuli and masked by camouflaging for social ones. This study demonstrates that the inhibitory gating deficit in high autistic trait females is not a global impairment but rather a stimulus-dependent one, highlighting the need to consider sex and stimulus type.

Children and adolescents with hearing loss frequently encounter reduced auditory access and delayed language development, factors that may influence the maturation of executive functions. This study examined developmental differences in planning, a core executive function, in 98 children and adolescents with hearing loss or normal hearing aged 7 to18 years using the Tower of London task. Compared to normal hearing peers, participants with hearing loss made more unnecessary moves and rule violations and initiated problem-solving more rapidly, suggesting reduced preplanning efficiency and increased impulsivity. These group differences were most pronounced in adolescents, who showed faster initiation and greater movement inefficiency than age-matched normal hearing participants. Within the hearing loss group, adolescents displayed higher accuracy and longer initiation times than children, reflecting developmental improvements despite persistent gaps relative to hearing peers. Language development age did not alter the main effects. Findings indicate that reduced early auditory and language access may contribute to differences in planning development, highlighting the need for targeted executive functions support in educational and clinical settings for youth with hearing loss.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition defined by differences in social communication and restricted, repetitive behaviours. As diagnostic criteria have broadened, ASD is now recognised across a wider range of individuals, raising key questions about its structure: does ASD have discrete sub-types, or is it better conceptualised as a continuous, possibly multidimensional, condition? We aim to explore whether a multidimensional continuum model more accurately captures the variability within ASD. We analysed a large SPARK phenotypic dataset of medical history and diagnostic surveys (background history, SCQ, RBS-R; n=36,710 individuals). We apply and compare two traditional statistical approaches, Factor Analysis and Gaussian Mixture Models, with a modern machine learning technique, the Variational Autoencoder (VAE). VAEs reconstructed unseen test data with ~4-fold better accuracy than Factor Analysis, and ~8-fold better accuracy than Gaussian Mixture Models. We identified four stable latent factors across 100 independently trained VAEs. These four dimensions provide an individual behavioural profile that can be visualized using radar-plots, offering a compact way to compare profiles at the person level. Through further analysis, we found evidence for 3 overlapping clusters or subtypes of ASD identified within the 4D latent space. This work aims to inform new ways of modelling ASD using a VAE that will be able to discern between a continuum or a clustered output and that go beyond binary diagnosis, instead reflecting the complex range of trait profiles, with implications for personalised diagnosis and intervention.

Background/Objectives. Autism spectrum disorder (ASD) has been associated with microbiome alterations, but the relative contribution of environmental and individual factors remains unclear. This study explored oral and gut microbiome profiles in environmentally matched dizygotic triplets discordant for ASD. Materials and Methods. Triplets in the 5-9 year age range, including one child with ASD and two neurotypical siblings, underwent standardized oral examination. Oral tongue-dorsum and rectal swab samples were analyzed by 16S rRNA sequencing. Taxonomic composition and beta diversity were evaluated descriptively. Results. Dominant bacterial phyla were broadly similar across siblings, but oral microbial profiles showed greater interindividual variation. The participant with ASD had the highest dental biofilm accumulation, predominance of Streptococcus, and reduced representation of several secondary genera. One neurotypical sibling with mild gingival inflammation showed greater representation of Fusobacterium, Prevotella, and Leptotrichia. Beta diversity demonstrated clearer interindividual separation among oral than gut samples. Conclusions. Individual-specific factors may influence microbiome patterns even under highly similar environmental and dietary conditions. These findings support further investigation of the oral microbiome as a complementary component of ASD microbiome research.

Background: Autism polygenic scores (PGS) reliably predict case-control status yet explain little variance in autism-related traits. Landscape accounts of neurodevelopmental diversity propose that genetic liability broadens the range of viable neural configurations rather than shifting brain organisation toward dysfunction. We tested whether autism polygenic load is associated with increased variability in functional network organisation among non-autistic adults. Methods: We analysed resting-state functional connectivity from 910 non-autistic adults (aged 22-35) in the Human Connectome Project. Polygenic scores were derived from the iPSYCH autism GWAS at a pre-specified threshold (p = 0.1). Modularity (segregation) and global efficiency (integration) were computed at a pre-selected parcellation size and density (100-node, 20%), and residualised for age, intracranial volume, and head motion. Variance effects were assessed by variance regression including a PGS-by-sex interaction, decile-stratified dispersion trends, and PGS-balanced bootstrap resampling. Edge-wise analyses used false discovery rate correction. Results: Modularity variability broadened with polygenic load in a sex-dependent manner (sex-by-PGS beta = 1.92e-4, p = 0.031). Decile trends (male minus female difference = 0.82, p = 0.034) and balanced-bootstrap trends (difference = 1.19, p = 0.032) both differed by sex: variance increased across polygenic bins in males (r = 0.57, one-tailed p = 0.021) but not females. No comparable effect emerged for global efficiency (all p >= 0.54). Polygenic scores showed no association with social-cognitive difficulty (beta = 0.11, p = 0.209), mean network organisation, or connectivity after correction. Limitations: All participants were non-autistic adults and the analysis was cross-sectional. The identified effects are small and the sample size not sufficient to resolve very small effects often reported in genetics studies. Characterisation of genetic effects in women may be influenced by biases in the data used to calculate polygenic scores. Conclusions: Autism polygenic load broadened modular network configurations in males without shifting mean organisation or its behavioural correlates, offering partial support for landscape accounts.

Generalization is a key cognitive process that allows humans to flexibly apply prior knowledge to guide new behaviors. Difficulties with generalization and flexibility are observed across neurodevelopmental disorders, especially autism, limiting adaptive function and quality of life. Cognitive-behavioral treatment benefits some but not all autistic individuals. As treatment requires application of learned skills to everyday life, variability in generalization ability may limit intervention success in autism. While cognitive substrates of learning and generalization are well established, their potential for explaining clinical outcomes is not known. Here, we combined a category learning task with computational modelling to distinguish two learning strategies underlying generalization -- prototype abstraction vs. exemplar memorization -- and tested whether individual differences in these learning strategies predicted real-world intervention outcomes in autistic youth. Fifty-four participants completed the category learning task at two pre-intervention timepoints, and then completed Unstuck and On Target:14-22 intervention targeting flexible problem solving, goal setting, and planning. We found that participants who consistently relied on prototype abstraction (N=26) were subsequently more likely to benefit from the intervention, showing improvement in parent- and self-reported flexibility. These findings identify prototype abstraction as a clinically relevant cognitive capacity that may help explain individual differences in intervention response and support the tailoring of interventions. More broadly, they demonstrate the value of linking basic cognitive mechanisms to clinical outcomes and may inform strategies to enhance the effectiveness of cognitive-behavioral interventions for youth with developmental disabilities.

Background: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition for which timely diagnosis is critical to early intervention, family support, and equitable access to care. However, substantial disparities in access to ASD diagnostic services persist across socioeconomic, geographic, clinical, and health-system contexts. This systematic review and meta-analysis synthesized evidence on determinants of access across the ASD diagnostic pathway, from recognition and referral to diagnostic completion and timely diagnosis. Methods: We systematically searched MEDLINE/PubMed, Embase, Scopus, Web of Science, Global Health, and grey-literature sources for studies published between January 2004 and December 2024. Eligible studies examined determinants of ASD diagnostic completion, diagnostic pathways, diagnostic timeliness, or barriers and facilitators to diagnostic access. Two reviewers independently extracted data and assessed methodological quality using the Mixed Methods Appraisal Tool (MMAT). Quantitatively comparable estimates were synthesized using random-effects models with restricted maximum likelihood estimation. Heterogeneity was assessed using Cochran's Q, I2, tau2, and 95% prediction intervals. Pre-specified subgroup analyses, meta-regression, sensitivity analyses, funnel-plot assessments, and Bayesian random-effects analyses were undertaken. Results: The search identified 4,899 records; after removal of 537 records without associated data, 4,362 records underwent title/abstract screening. 3,800 records were excluded, 562 reports were sought for retrieval, and 450 full-text reports were assessed after 112 could not be retrieved. Ultimately, 22 unique studies met the inclusion criteria. Nine unique studies contributed 23 quantitative effect estimates, while the remaining studies contributed to the narrative synthesis. The evidence covered socioeconomic, geographic, family, communication, screening, child developmental, provider, and health-system determinants. The overall random-effects meta-analysis yielded a pooled diagnostic access outcome of 74.1% (95% CI 65.8-81.1%), with substantial heterogeneity (Qe=209.95, p<0.001; I2=88.4%, 95% CI 79.1-94.4%; tau2=0.691) and a wide 95% prediction interval of 32.8-94.4%. Bayesian analysis produced a highly concordant pooled estimate of 73.3% (95% CrI 65.3-80.2%), with I2=87.5% and tau=0.833, and satisfactory MCMC convergence (R-hat=1.000). By outcome domain, pooled successful outcomes were highest for diagnostic pathways (89.3%, 95% CI 70.1-96.7%), followed by timely diagnosis (76.3%, 95% CI 62.9-86.0%), and lowest for diagnostic completion (67.1%, 95% CI 61.8-72.0%) (Qm=5.98, p=0.050). Timely diagnosis demonstrated particularly high heterogeneity (I2=91.2%), whereas diagnostic completion showed moderate heterogeneity (I2=40.6%). Across determinant domains, frequentist pooled estimates were 79.5% for child developmental/neurobehavioral factors, 74.2% for family/socioeconomic/perceptual factors, 68.0% for intervention/care-navigation factors, and 63.6% for provider/clinical recognition factors. Bayesian estimates were 76.7% (BF=53.76), 72.9% (BF=226.32), 64.3% (BF=25.60), and 53.7% (BF=0.684), respectively. Meta-regression indicated that determinant category (Qm=13.48, p=0.004) and effect measure (Qm=7.81, p=0.020) significantly explained between-study variation, whereas age group (p=0.203) and geographic region (p=0.453) did not. Family/socioeconomic factors had significantly larger effect sizes (B=2.703, 95% CI 0.661-4.744; p=0.009), as did child developmental/neurobehavioral factors (B=1.516, 95% CI 0.047-2.985; p=0.043). Potential small-study effects were detected by two of three asymmetry tests, although the Rosenthal fail-safe N was 1,723. Trim-and-fill identified seven potentially missing estimates, with an adjusted pooled effect of 68.4% (95% CI 27.7-109.1%). Importantly, exclusion of two influential outlying estimates produced a pooled outcome of 77.1% (95% CI 71.6-81.9%), indicating that the principal finding was robust. Conclusions: Approximately three-quarters of observed ASD diagnostic outcomes represented successful access, but the substantial heterogeneity indicates that diagnostic access is highly context-dependent. Families were more likely to successfully navigate diagnostic pathways than to complete diagnostic assessment, while timely diagnosis showed the greatest variability across settings. Family and socioeconomic circumstances and child developmental characteristics emerged as particularly important determinants, whereas provider-related effects were more heterogeneous and uncertain. Improving equitable ASD diagnosis requires interventions spanning the entire diagnostic pathway, including developmental surveillance, screening, referral coordination, family navigation, provider capacity, specialist availability, and mechanisms to ensure completion of diagnostic assessment. Greater longitudinal and implementation research is particularly needed in low- and middle-income countries, where diagnostic infrastructure and specialist capacity remain limited.

Metastability is a fundamental dynamical property of large-scale brain networks and reflects the capacity of the brain to flexibly reorganize transient coordination patterns. In this study, we investigated whether metastable properties of resting-state electroencephalographic (EEG) phase synchronization networks are associated with individual differences in autistic traits. Resting-state EEG data from 88 neurotypical adults were analyzed using two complementary metrics: synchrony coalition entropy (SCE), which quantifies the diversity of transient phase synchronization patterns, and the metastability index (MSI), which quantifies temporal variance in global phase synchronization. SCE showed frequency-specific associations with the Autism-Spectrum Quotient (AQ) attention-switching subscore at 18-24 Hz and the communication subscore at 4-8 Hz, suggesting that frequency- and network-specific patterns of metastable synchronization are associated with distinct aspects of autistic traits. In contrast, MSI showed a modest association with the social-skill subscore in the lower-beta range, but this effect did not survive a cluster-based permutation test. This exploratory observation suggests that global synchronization variability may capture a weaker, complementary aspect of trait-related metastable dynamics. These findings suggest that, within a neurotypical population, individual differences in autistic traits may be more sensitively captured by the repertoire of transient phase synchronization patterns, as indexed by SCE, than by global phase synchronization variability, as indexed by MSI. Moreover, the associations of distinct AQ subscores with SCE in different frequency ranges suggest that different dimensions of autistic traits may be related to metastable network dynamics operating at different temporal scales. Author SummaryThe brain constantly coordinates activity across many regions, and this coordination changes over time rather than remaining constant. Understanding these dynamic patterns is important for explaining individual differences in cognition and behavior. In this study, we focused on a dynamical property called "metastability," which describes how brain activity flexibly shifts between different patterns of coordination. Instead of remaining in a stable state, the brain repeatedly forms and dissolves coordinated activity across regions. We analyzed brain signals recorded with resting-state electroencephalography (EEG) and examined whether these dynamic patterns were related to individual differences in autistic traits. We found that different aspects of time-varying coordination were linked to different dimensions of autistic traits in a neurotypical population. These findings suggest that examining how brain activity changes over time, rather than relying only on time-averaged measures, can reveal neural features associated with individual differences in autistic traits. Our study highlights metastability as a useful concept for understanding the flexible and dynamic nature of human brain function.

Purpose: There is a long-standing perception that individuals who stutter are less intelligent, with the disfluencies unique to stuttered speech often assumed to be the overt reflection of lower intelligence, despite no supporting evidence. The purpose of the present study was to explore the validity of this assumption by examining the cognitive abilities of adults who stutter compared to the general population using the NIH Toolbox (C) Cognition Battery (NIHTB-CB). Method: Sixty-three adults who stutter completed the NIHTB-CB, which includes seven standardized measures assessing crystallized cognition (Picture Vocabulary, Oral Reading) and fluid cognition (List Sorting Memory Test, Pattern Comparison Processing Speed Test, Flanker Inhibitory Control Test, Dimensional Change Card Sort Test, Picture Sequence Memory Test). The NIHTB-CB generates t-scores adjusted for demographic variables based on a large sample of neurotypical adults. Results: Composite scores of overall cognition for adults who stutter were not statistically equivalent, rather, their scores were higher than the general population. Higher scores were driven by crystallized cognition, with significantly higher scores on Oral Reading subscale. Conclusions: Present findings demonstrate that adults who stutter possess cognitive skills that are comparable to or potentially higher, than the general population. These results challenge the misconception that stuttering reflects diminished intelligence and offer evidence to mitigate stereotype threat.

Background: Autistic Chronic Energy Depletion Syndrome, commonly referred to as Autistic Burnout, is a debilitating condition characterized by exhaustion, loss of function, and reduced tolerance to stimuli. While several instruments attempt to measure it, validation studies have only used cross-sectional designs and/or convenience samples with low support needs, limiting understanding of their performance across heterogeneous, autistic populations and over time. Methods: Using a community-based participatory research (CBPR) approach, we revised the 27-item AASPIRE Autistic Burnout Measure (AABM) into a 14-item AASPIRE Autistic Burnout Measure-Revised (AABM-R) and tested it in a longitudinal study of 835 autistic adults recruited from healthcare systems, disability services, and the community. Participants completed surveys directly (with or without support) or via a caregiver. We assessed structural validity and measurement invariance using exploratory and confirmatory factor analysis, tested construct validity through a priori hypothesis testing, examined discriminant validity from depression using longitudinal factor analysis and cross-lagged panel models, and assessed criterion validity using ROC analysis. Results: The AABM-R demonstrated a clear single-factor structure among direct reporters, with and without support, and measurement invariance across these groups; findings were less conclusive for the smaller caregiver-report subsample. Autistic burnout correlated as hypothesized with stressors (e.g., discrimination, masking, adverse childhood experiences), supports (e.g., social support, receiving needed help with daily living activities), and broader outcomes (e.g., quality of life, depression, anxiety). Longitudinal modeling supported autistic burnout as empirically distinct from, though related to, depression. ROC analysis (AUC = 0.89) supported cut-offs distinguishing probable (33-56, LR 7.38), unsure, and unlikely (0-22, LR 0.15) burnout. Conclusions: The AABM-R is a brief, accessible, psychometrically sound measure of autistic burnout suitable for heterogeneous autistic populations, with preliminary clinical cut-offs to guide screening. Further research is needed on the caregiver-report version and on longitudinal predictors and outcomes of burnout.

Gastrointestinal (GI) conditions are common among children with neurodevelopmental disabilities (NDDs), and are associated with functional impairment, behavioral symptoms, and increased health care utilization. A unique relationship between autism and GI dysfunction has been proposed, leading to a focus on autism in GI research, management guidelines, and clinical tool development. Leveraging >20 years of electronic health record data and a cohort of 42,204 cases with attention-deficit/hyperactivity disorder, autism, cerebral palsy, epilepsy, or intellectual disability and 297,402 controls without NDDs, we quantified associations between NDDs and GI conditions in children. GI conditions were more common in cases than controls across all individual NDDs; intellectual disability and cerebral palsy were most strongly associated with having a GI condition. In this work, clinically recognized GI morbidity was elevated across all NDDs and not unique to autism, suggesting that a broader, transdiagnostic approach to GI dysfunction in children with NDDs is warranted.

Background and aimVery preterm birth (VPT; [&le;]32 weeks gestation) is associated with an increased risk of later psychiatric disorders, including psychosis. Although psychosis typically emerges in adulthood, subclinical early signs along the psychosis continuum, such as psychotic-like experiences (PLEs), can be observed much earlier. We therefore aimed to study PLEs in childhood in VPT individuals recruited from a clinical cohort compared with full-term (FT) controls. We subsequently investigated whether findings could be replicated in an independent population-based cohort. MethodsPrimary analyses were conducted in the Brain, Immunity and Psychopathology (BIPP) study, including 197 children born VPT recruited through Neonatal Intensive Care Units and 72 FT controls assessed at a mean age of 10.50{+/-}1.77 years. Between-group differences in PLEs were then examined in the Adolescent Brain Cognitive Development (ABCD) study, including 149 children born VPT and 9519 FT controls assessed at a mean age of 9.94 {+/-} 0.63 years. PLEs were assessed using the Prodromal Questionnaire-Brief Child Version (PQ-BC), yielding frequency and distress-related scores for both the total scale and three specific domains (unusual thought content, perceptual abnormalities, disorganised speech). Regression models tested associations between birth status (VPT and control) and PQ-BC scores adjusting for age, sex, and socio-economic status, with secondary models additionally adjusting for cognitive ability and broader psychopathology. Pooled analyses examined cohort effects (BIPP and ABCD) and cohort-by-group status (VPT and control) interactions. ResultsIn BIPP, VPT birth was associated with higher PQ-BC total ({beta}=1.61, p=0.004) and distress scores ({beta}=0.78, p=0.039), with the strongest and most consistent associations observed for perceptual abnormalities across total score (sum of endorsed items), distressing items, and distress severity scores (all p[&le;]0.01). These associations were attenuated but largely persisted after adjustment for cognitive ability and broader psychopathology, particularly for perceptual abnormalities. In ABCD, VPT birth was not significantly associated with global or domain-specific PQ-BC outcomes. DiscussionVPT birth is associated with increased vulnerability to PLEs in childhood, particularly in the domain of perceptual abnormalities. The lack of clear replication in the population-based ABCD cohort may reflect differences in the composition of its VPT subgroup, which may not fully represent VPT individuals typically seen in clinical cohorts.