Autism Research

BackgroundThe 40Hz auditory steady-state response (ASSR) is a measure of gamma-band neural synchrony sensitive to excitation-inhibition (E/I) balance. Disruptions to E/I balance have been implicated in autism spectrum disorder (ASD), making ASSR an efficient tool for investigating neural synchrony development in this population. Whether age-related differences in 40Hz ASSR are detectable across development in ASD remains understudied. Phelan-McDermid syndrome (PMS), a rare genetic disorder with a phenotype overlapping with autism, caused by SHANK3 disruption, provides a genetically defined model for further investigating E/I-related neural synchrony disruptions. MethodsWe examined 40Hz inter-trial phase coherence (ITPC) as an index of neural synchrony across a wide age range (2-37 years) in 127 participants from four groups: TD (n=43), ASD without intellectual disability (w/o ID; n=37), ASD with intellectual disability (w/ID; n=24), and PMS (n=23). Given the distinct age and cognitive profiles of ASD subgroups in this sample, analyses were conducted in separate models: TD vs. ASD w/o ID across all ages, and TD vs. ASD w/ID vs. PMS restricted to participants under 18. ResultsFor the first time in a cross-sectional sample spanning a large age range, we show that 40Hz ITPC increases significantly with age in TD individuals, while this developmental trajectory is absent in ASD without intellectual disability. Among children and adolescents under 18, 40Hz ITPC did not differ across TD, ASD w/ID, and PMS, and IQ did not predict ITPC in clinical groups. A post-hoc analysis revealed higher ITPC in TD males than females, with no sex differences in ASD or PMS. ConclusionsWe demonstrate that gamma-band ITPC trajectories diverge between TD and ASD, specifically in adulthood, with no such difference detectable in childhood. No significant group differences were found among TD, ASD w/ID, and PMS individuals under 18. These findings highlight the importance of age as a critical variable when measuring ASSR, and underscore the need for lifespan studies, particularly in genetically defined conditions such as PMS, to determine whether similar divergence emerges in adulthood.

Communication deficits are a defining feature of autism spectrum disorder (ASD) and among the earliest detectable markers of atypical neurodevelopment. Yet how specific genetic ASD risk factors shape the developmental trajectory of vocal communication remains poorly understood. Fragile X syndrome (FXS) is the most common inherited cause of ASD, resulting from the transcriptional silencing of the FMR1 gene, and a majority of FXS individuals exhibit impaired language development and atypical vocal communication. Rodent ultrasonic vocalizations (USVs) produced during maternal isolation provide a tractable model for studying the developmental trajectory of early vocal communication in FXS. Here, we characterized isolation- induced USVs in Fmr1 knockout (KO) and littermate wildtype (WT) rats from postnatal days 3- 21 to determine whether Fmr1 mutation disrupts the acoustic structure, temporal organization, or sequential syntax of USVs across postnatal development. We found that Fmr1 KO rat pups exhibited reduced call number during the peak developmental window for isolation-induced calling (p6-p10), while acoustic structure and temporal organization were largely preserved. Network analysis of call transitions revealed that WT pups exhibited a progressive increase in syntactic complexity from p3-p10. However, this developmental trajectory was significantly altered and delayed in Fmr1 KO pups. Together, these findings demonstrate that Fmr1 mutation not only disrupts vocal production but the developmental expansion of syntactic flexibility in rats, highlighting USV syntax as a sensitive marker of atypical communicative development in FXS models.

Reported perceptual differences in autism may arise from reduced use of prior context to shape incoming sensory input. Speech perception provides a critical test of this account because stable perception requires listeners to integrate variable acoustic signals with contextual expectations. This study examined context-dependent modulation of speech encoding in autistic and non-autistic adults using the frequency-following response (FFR), a neurophysiological measure of phase-locked auditory encoding. Participants heard English intonational pitch contours presented in repetitive and variable contexts while EEG was recorded. Principal component analysis of FFR metrics yielded components indexing neural encoding fidelity and timing. Non-autistic participants showed enhanced encoding fidelity in more predictable contexts, whereas autistic participants showed reduced context-dependent modulation. Neural encoding timing also showed divergent context effects across groups, suggesting altered balance between feedback-based predictive mechanisms and locally driven adaptation processes. Within the autistic group, greater context-related modulation of encoding fidelity was associated with lower ADOS-2 Social Affect severity but poorer speech-in-noise perception, suggesting that the functional impact of contextual modulation depends on input reliability and task demands. These findings indicate that context-dependent modulation of speech encoding is altered in autism and may contribute to individual differences in auditory and social-communicative function.

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.

PurposeInterpersonal entrainment, defined as the tendency of interacting individuals to temporally align their behaviours, is considered a key mechanism supporting social interactions through predictive and multisensory processes. Autism Spectrum Disorder (ASD), characterized by social and communication difficulties, has been associated with atypical predictive and multisensory integration processes, which may affect spontaneous entrainment to others actions during rhythmic interactions. MethodsThe present study investigated spontaneous interpersonal entrainment in 24 autistic and 22 neurotypical young adults using a unidirectional adaptation of the drifting metronomes paradigm developed by Rosso et al. (2021). Participants synchronized their finger tapping with an auditory metronome while either seeing or not seeing a partners hand movements performing the same task at a slightly different tempo. Individual synchronization performance was assessed using asynchrony measures and computational modelling of sensorimotor synchronization, while interpersonal coordination dynamics were quantified using joint recurrence analysis. ResultsVisual exposure to the partners hand movements significantly increased tapping variability while simultaneously enhancing spontaneous interpersonal entrainment. Contrary to previous findings, these effects were comparable across groups, suggesting similar sensitivity to spontaneous low-level interpersonal coupling under stable and predictable conditions. ConclusionOverall, the findings support accounts proposing selective rather than generalized atypicalities in predictive processing and interpersonal entrainment in ASD.

Although language acquisition delays are frequently observed in children with autism spectrum disorder (autism), our current understanding of the neurobiological mechanisms underlying language development in autism is sparse. Previous studies have found resting-state electroencephalography (EEG) power to be associated with language abilities in autistic children. However, longitudinal studies examining resting-state EEG phase coherence in relation to language development in preschool-aged children with autism are limited. This study aimed to characterize age- and group-related changes in whole-brain coherence in neurotypical children and in autistic children with and without language delay. Resting-state EEG and language data were collected at 2, 3, and 4 years of age. Peak phase coherence within the alpha band (6-11 Hz) was calculated at each timepoint and differences in the developmental trajectory of peak alpha coherence (PAC) were analyzed. In neurotypical children, PAC increased between 2 and 4 years of age. In contrast, PAC did not significantly change with age in children with autism. However, when examining autistic children based on language delay status, PAC increased with age in autistic children without language delay, but not in children with language delay. Exploratory analysis revealed evidence for an interaction between PAC and age, suggesting that the direction of the association between PAC and VDQ varied across age. Overall, these results support previous findings of altered oscillatory connectivity in autism and suggest that differences become apparent early in development. Importantly, phase coherence may not only differentiate diagnostic groups but also capture meaningful variability within the autism group. Future research should further investigate the use of EEG coherence as a biomarker of language development in autism.

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.

Bayesian accounts of autism propose that perception is less influenced by prior expectations and more strongly driven by incoming sensory information in autistic than non-autistic individuals, with this altered balance cascading through the cognitive hierarchy to also influence higher cognitive functions. However, empirical support for these accounts remains mixed. Previous work has mostly tested these ideas in the context of objective environmental statistics, but recent work suggests that it may be subjective experience of structure, rather than structure itself, that shapes perceptual processing. Characterising these subjective experiences in autistic individuals is therefore crucial for understanding predictive processing in autism. In the present study, we thus examined subjective experience of statistical structure in autistic and non-autistic adults and tested how this experience relates to perceptual decisions. Participants were exposed to statistical regularities between action cues and visual stimuli (shapes), and we measured their speed and accuracy in reporting which shape they had seen. At the end of the study, participants were asked to estimate the probability and rate their surprise for each action-shape combination. Autistic and non-autistic participants showed similar subjective probability and surprise ratings and a comparable relationship between these ratings and perceptual decisions. Across participants, subjective ratings explained perceptual decisions better than objective structure. Together, these findings show that autistic and non-autistic adults experience statistical structure similarly, with these experiences exerting a similar influence on perceptual decisions - therefore suggesting that subjective experience plays a comparable role in predictive processing in autistic and non-autistic adults.

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.

The Quebec 1000 Families (Q1K) platform has been designed to recruit, phenotype, and collect biospecimens from a large cohort of families with at least one member with autism spectrum disorder or a related neurodevelopmental condition. As part of the Q1K protocol, an experimental test battery was developed and validated using simultaneous high-density electroencephalography (EEG) and eye tracking (ET). We report on the general approach and design principles, multimodal EEG/ET integration, the tasks, and their validation, providing a blueprint for implement such a project. It also describes the cohort and its methods as a reference for future studies using this dataset. By releasing openly this experimental test battery, we aim to support task standardization and multi-project data pooling in autism and related neurodevelopmental disorders.

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.

Purpose: Autism spectrum disorder (ASD) is genetically and phenotypically heterogeneous condition, complicating identification of causal variants. Current diagnostic approaches, have limited diagnostic yield, underscoring the need for new strategies. Methods: We developed a phenotype-driven framework to prioritize ASD-associated genetic variants using comprehensive phenotypic and exome sequencing (ES) data from 125 children with ASD. We used the Human Phenotype Ontology (HPO) nomenclature to prioritize candidate variants in each child based on the similarity between its observed phenotypes and variant-specific expected phenotypes. Results: We identified 228 HPO terms grouped into 41 phenotype categories. ASD-associated genes, according to HPO and SFARI Gene databases, were significantly enriched with these phenotypes compared to non-ASD genes (mean 16.1+/-5.7 vs. 6.5+/-5.4; p=1.1e-231; HPO, and 16.0+/-6.7 vs. 7.3+/-6.0; p=2.1e-57; SFARI) supporting the relevance of this phenotype battery to ASD genetics. In 36 genetically resolved participants, the phenotype-similarity approach ranked 58% of causal variants first and 89% within the top three. In the 89 unresolved cases, it highlighted six novel clinically relevant variants, thus increasing the diagnostic yield by 45%. Conclusions: Our novel ASD phenotype battery facilitates prioritization of clinically relevant ASD variants and hence may enhance diagnostic yield, gene discovery, and phenotype-guided precision medicine of ASD.

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 The global prevalence of autism spectrum disorder (ASD) has significantly increased over the past two decades. Despite substantial research advances, critical aspects, including etiology, diagnostic biomarkers, and pharmacological interventions, remain incompletely elucidated. This persistent knowledge gap warrants systematic mapping of the field's evolution to inform future research priorities. Methods A bibliometric analysis of ASD-related publications indexed in Web of Science was conducted from January 2020 to May 2025. Following a systematic deduplication process, original articles, reviews, case reports, and clinical trials were included in the analysis. The analytical framework comprised co-authorship networks, institutional collaboration patterns, national research contributions, and keyword co-occurrence structures, all of which were examined using CiteSpace (version 5.8.R3) and VOSviewer. Results After deduplication, 8,162 publications (January 2020-May 2025) were analyzed. The annual output grew steadily, confirming ASD as a sustained priority in neuroscience. Research remains academia-driven, led by the United States, with China as the second-largest contributor. Chinese institutions place greater emphasis on mechanistic and developmental phenotyping, which aligns with national priorities. These studies maintain strong methodological rigor, and their growing volume underscores the central role of ASD in translational neuroscience. Conclusion Future research on ASD should focus on strengthening case identification, refining clinical phenotyping, and expanding large-scale cohort studies to advance our understanding of its etiology and identify reliable diagnostic biomarkers. It is equally important to develop and evaluate targeted interventions for core symptoms and integrate telemedicine into service delivery models. A critical yet understudied priority is improving the quality of life for autistic individuals and their families, an area in which research globally, including in China, requires greater depth and consistency. With China's growing investment in autism research, it is well-positioned to contribute to these pressing international challenges.

Autism spectrum disorder (ASD) is characterized by differences in social communication, interaction, and restricted and repetitive behaviors. The hypothesis that ASD involves altered cortical excitation-inhibition (EI) balance has been extensively investigated, yet evidence remains mixed, partly because EI balance changes substantially during typical maturation. We used resting-state magnetoencephalography (MEG) to examine developmental trajectories of cortical EI alterations with regional specificity in a large cross-sectional cohort (N = 172; 92 typically developing, 80 ASD; ages 6-32). Functional EI (fEI), derived from critical brain dynamics, was estimated across 500 cortical parcellations. Group-averaged fEI maps revealed broadly similar large-scale topographic patterns across groups. Age-stratified analyses revealed increased global fEI in childhood and decreased fEI in adolescence in ASD, with no evidence of a group difference in adulthood. Parcel-wise regressions identified a significant main effect of diagnosis in right dorsolateral prefrontal cortex, where typically developing individuals showed higher fEI across all ages. A significant group-by-age interaction in left inferior parietal cortex indicated diverging developmental trajectories. Finally, fEI in paracentral and precuneus regions was associated with the magnitude of ASD symptoms. These findings indicate that EI imbalance in ASD is neither globally distributed nor static, but expressed through regionally and developmentally specific differences, with relevance for ASD heterogeneity.

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.

Background: Previous large-scale structural MRI analyses of the brain in autism have identified gray matter (GM) differences when using region-of-interest analyses based on gross anatomical regions. However, such analyses have limited spatial specificity for localizing neuroanatomical alterations and may obscure subtle, spatially focal differences. Whole brain voxel-based morphometry (VBM) analyses enable greater spatial precision for localizing GM and white matter (WM) alterations in autism. Purpose: To rigorously identify voxel-wise GM and WM volume differences in autism in the largest VBM mega-analysis to date. Materials and Methods: This retrospective mega-analysis included structural 3D volumetric T1-weighted MRI brain scans from 3,051 participants (1,519 autism; 1,532 neurotypicals) collected across 51 sites/scanners. Voxel-wise GM and WM volumes were quantified using the ENIGMA CAT12 VBM pipeline. Linear mixed-effects regression was performed at each voxel to evaluate the association between diagnostic group and voxel-wise volume while adjusting for standard nuisance covariates Results: A total of 3,051 participants (15.0 {+/-} 8.2 yrs; 2,342 male) were included in the study. Autism was associated with widespread lower GM volume involving cortical, subcortical, and cerebellar regions. The most extensive alterations in autism were detected in the orbitofrontal cortex, amygdala, thalamus, and posterior lobes of the cerebellum. WM volume was lower in autism across major projection, commissural, association, and cerebellar/brainstem tracts, including the corona radiata, internal capsule, corpus callosum, and cerebellar peduncles. These findings remained consistent in sensitivity analyses, including the application of increasingly strict motion exclusion criteria. Conclusion: Autism is associated with smaller voxel-wise GM and WM volume involving widespread cortical, subcortical, and cerebellar regions. Our findings remained robust across supplementary analyses and provide high-resolution localization of structural brain differences in autism. These findings support the involvement of distributed neural systems underlying reward processing, sensory integration, and motor functioning in autism.