Molecular Autism最新文献

{"title":"Exome sequencing in severe non-syndromic specific learning and language disorders in a French cohort.","authors":"Eléonore Viora-Dupont, Julian Delanne, Aurore Garde, Sophie Nambot, Estelle Colin, Marie Bournez, Clémence Fauconnier-Fatus, Caroline Racine, Clément Simao De Souza, Céline Bernard, Agnès Maurer, Aurélie Espitalier, Christine Binquet, Marion Bouctot, Marie-Laure Humbert, Anne-Sophie Briffaut, Véronique Darmency, Patricia Plumet, Audrey Cotinaud-Ricou, Noémie Relin, Patrick Callier, Anne-Laure Mosca-Boidron, Nathalie Marle, Frederic Tran Mau-Them, Anne-Sophie Denommé-Pichon, Hana Safraou, Antonio Vitobello, Christophe Philippe, Yannis Duffourd, Ange-Line Bruel, Christel Thauvin-Robinet, Laurence Faivre","doi":"10.1186/s13229-025-00688-8","DOIUrl":"10.1186/s13229-025-00688-8","url":null,"abstract":"<p><p>BACKGROUND: Specific learning disorders (SLDs) affect approximately 5% of school-age children. In France, genetic investigations of complex non-syndromic SLD cases include chromosomal microarray analysis and fragile X syndrome testing. However, the examples of genes being described in intellectual disability or autism spectrum disorder and also reported in patients with complex and severe SLDs are multiplying. International efforts using exome sequencing have identified monogenic diseases that explain severe SLDs in some instances. The aim of our study was to investigate the value of exome sequencing in children with SLDs without intellectual disability and autism spectrum disorder. METHODS: We initiated a prospective study using exome sequencing in patients with well-documented, severe SLD. RESULTS: Analysis of 82 patients revealed pathogenic/likely pathogenic variants in 11 (13.4%) patients (ADNP, BRAF, CREBBP, KCNN2, KIF1A, RERE, SCN8A, SET, SMARCC2 (x2), TRIO). In addition, 38 variants of uncertain significance in candidate genes for severe neurodevelopmental disorders (NDDs) or in genes of unknown significance that could contribute to the phenotype were identified in 30 patients. LIMITATIONS: The study of 82 patients does not provide sufficient statistical power to conclude that exome testing adds value over chromosomal microarray analysis, or to determine which patient profiles are more likely to benefit from genetic testing. Studies with larger patient numbers are needed to increase statistical power. CONCLUSIONS: This study confirms the involvement of NDD genes in milder phenotypes and suggests the potential of exome sequencing for diagnosing severe SLDs. Further research on larger samples is required to determine which SLDs are most likely to benefit from pangenomic explorations and to clarify the implication of candidate variants.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"54"},"PeriodicalIF":5.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in axon pruning and myelination may alter neural signaling in autism spectrum disorder.","authors":"Kari L Hanson, Thomas Avino, Sandra L Taylor, Karl D Murray, Cynthia M Schumann","doi":"10.1186/s13229-025-00684-y","DOIUrl":"10.1186/s13229-025-00684-y","url":null,"abstract":"<p><strong>Background: </strong>Neuronal connectivity is refined throughout development by the proliferation and pruning of axons in cerebral white matter, and progressive axon myelination that enables rapid communication across brain regions. Differences in connectivity have been observed in autism spectrum disorder (ASD), including changes in white matter volume and connectivity. In the prefrontal cortex, this includes imbalances between short- and long-ranging axons, consistent with a pattern of local hyperconnectivity, and long-range hypoconnectivity. Alterations in temporal lobe white matter development-critical for social behavior-may contribute to atypical neural connectivity.</p><p><strong>Methods: </strong>We used electron microscopy to analyze 54 samples of temporal lobe white matter from 27 age-matched postmortem brains from males with ASD and neurotypical (NT) controls, ages 2-44 years. Defined regions of superficial (SWM) and deep (DWM) white matter were sampled from superior temporal (STG) and fusiform (FG) gyri. Axon density and myelin thickness were quantified, with axon size classified by inner diameter, to evaluate age-related differences between ASD and neurotypical brains.</p><p><strong>Results: </strong>In neurotypical control brains, total axon density significantly decreases with age in both STG and FG SWM. Although ASD cases show a similar trend, the density of small axons in STG is significantly higher than in controls. However, FG SWM in ASD shows no significant change in small-diameter axon density with age in this region. In neurotypical brains, myelin thickness of large-diameter axons increases significantly with age in STG and FG SWM. In contrast, large-diameter axons in ASD display significantly thinner myelin sheaths than controls across both STG and FG regions.</p><p><strong>Conclusions: </strong>The temporal lobe exhibits atypical patterns of white matter development in ASD. In neurotypical individuals, decreased axon density in SWM with age reflects effective neural pruning and refinement of local and short-range connectivity. In contrast, individuals with ASD maintain a high density of small-diameter axons in STG SWM, suggesting reduced pruning that results in local overconnectivity. Moreover, myelin thickness in SWM does not increase with age in ASD, implying reduced efficacy of neurotransmission. These alterations in white matter ultrastructure may contribute to the atypical connectivity and neural communication observed in ASD across the lifespan.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"53"},"PeriodicalIF":5.5,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Developmental Assessment of Social Communication Ability (DASCA): initial creation and psychometric description.","authors":"Aaron J Kaat, Audrey Thurm, Cristan Farmer, Shuting Zheng, Sheila Ghods, Stelios Georgiades, Stephen Kanne, Shrikanth Narayanan, Somer L Bishop","doi":"10.1186/s13229-025-00683-z","DOIUrl":"10.1186/s13229-025-00683-z","url":null,"abstract":"<p><strong>Objective: </strong>The dearth of tools to quantify and track growth in social communication ability has been a barrier to understanding and monitoring treatment outcomes for neurodevelopmental disorders. We undertook a multi-staged, multisite study to create the Developmental Assessment of Social Communication Ability (DASCA), a new measure explicitly developed as a clinical outcome assessment for monitoring change-both over the course of development and in response to treatment.</p><p><strong>Methods: </strong>The DASCA is a caregiver-report instrument created using a mixed-methods approach. Qualitative components of this approach included focus groups and cognitive debriefing interviews. Quantitative components included dimensionality analysis, differential item functioning, and item response theory modeling. The item bank was iteratively refined to assess social communication skills that are typically acquired by early- to middle- childhood.</p><p><strong>Results: </strong>The final DASCA item bank contains 184 items. Expressive language was a major factor in determining the appropriateness of some items for certain groups of children. Negligible differential item functioning, primarily by age, was observed for some items. However, impact analyses determined that this differential item functioning did not meaningfully impact overall scores.</p><p><strong>Limitations: </strong>Given that sample size limitations prevented us from using separate samples for exploratory and confirmatory phases of modeling, it will be important to gather additional validity evidence in independent samples, especially as the current data were collected during the COVID-19 pandemic.</p><p><strong>Conclusion: </strong>The DASCA holds promise as an outcome measure for assessing changes in social communication ability. Ongoing development efforts include creating a computer adaptive test administration to allow for serial assessments using different item sets to yield a consistent score that is sensitive to change.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"52"},"PeriodicalIF":5.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12529783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype correlations with autism spectrum disorder-related traits in noonan syndrome and noonan syndrome with multiple lentigines: a cross-sectional study.","authors":"Chloe Alexa McGhee, Julia R Plank, Luca Pannone, Odeya Russo, Naomi Fuhrmann, Aurora Ruggeri, Francesca Clementina Radio, Simone Martinelli, Marco Tartaglia, Tamar Green","doi":"10.1186/s13229-025-00681-1","DOIUrl":"10.1186/s13229-025-00681-1","url":null,"abstract":"<p><strong>Background: </strong>Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are neurodevelopmental conditions caused by genetic variants leading to upregulated signaling in the RAS-MAPK pathway. While previous research has focused on genetic variability in cognitive and cardiac phenotypes, behavioral phenotypes, and their correlations across genetic variants and within the PTPN11 gene remain poorly characterized.</p><p><strong>Methods: </strong>This study included 121 individuals with NS (PTPN11: 88, SOS1: 18, RAF1: 6, KRAS: 2, RIT1: 3, NRAS: 2, LZTR1: 2, SOS2: 1) and seven individuals with NSML (PTPN11), compared to age- and sex-matched typically developing (TD) (N = 71). Behavioral questionnaires assessed social responsiveness and ASD-related traits (using SRS-2), and emotional problems (using CBCL) to identify genetic variant-specific behavioral profiles. Biochemical profiling of SHP2 activity in PTPN11-associated NS variants examined genotype-phenotype relationships.</p><p><strong>Results: </strong>Compared to TD individuals, those with PTPN11-associated NS, NSML, and SOS1-associated NS exhibited clinically elevated scores, indicating increased ASD-related behaviors, poorer social functioning, and heightened emotional problems. Genetic variant comparisons revealed that individuals with PTPN11-associated NS and NSML exhibited greater ASD-related challenges than those with RAF1. Individuals with NSML exhibit elevated attention problems compared to all other genetic groups. Logistic regression results suggested each one-unit increase in SHP2 fold activation for PTPN11-associated NS corresponded to a 64% higher likelihood of markedly elevated restricted and repetitive behaviors, suggesting genotype-phenotype links.</p><p><strong>Limitations: </strong>Small sample sizes for rarer variants, leading to unequal group sizes across subgroups, with PTPN11 variants comprising most of the NS group. Future research should address these sampling constraints and conduct functional studies to clarify variant impacts. Longitudinal assessments could elucidate behavioral phenotype trajectories.</p><p><strong>Conclusions: </strong>This study underscores the importance of genetic variant-specific research to understand unique behavioral phenotypes in NS and NSML. Our findings indicate a higher risk for ASD-related symptoms in PTPN11-associated NS and NSML compared to other variants. Additionally, individuals with PTPN11-associated NS and higher SHP2 fold activation exhibited greater impairments in restricted and repetitive behaviors, suggesting SHP2 activation variations may contribute to phenotypic variability. By linking ASD-related symptoms to biochemical predictors in PTPN11-associated NS, this study may inform future targeted treatment approaches.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"51"},"PeriodicalIF":5.7,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing three algorithms of automated facial expression analysis in autistic children: different sensitivities but consistent proportions.","authors":"Liora Manelis-Baram, Tal Barami, Michal Ilan, Gal Meiri, Idan Menashe, Elizabeth Soskin, Carmel Sofer, Ilan Dinstein","doi":"10.1186/s13229-025-00685-x","DOIUrl":"10.1186/s13229-025-00685-x","url":null,"abstract":"<p><strong>Background: </strong>Difficulties with non-verbal communication, including atypical use of facial expressions, are a core feature of autism. Quantifying atypical use of facial expressions during naturalistic social interactions in a reliable, objective, and direct manner is difficult, but potentially possible with facial analysis computer vision algorithms that identify facial expressions in video recordings.</p><p><strong>Methods: </strong>We analyzed > 5 million video frames from 100 verbal children, 2-7 years-old (72 with autism and 28 controls), who were recorded during a ~ 45-minute ADOS-2 assessment using modules 2 or 3, where they interacted with a clinician. Three different facial analysis algorithms (iMotions, FaceReader, and Py-Feat) were used to identify the presence of six facial expressions (anger, fear, sadness, surprise, disgust, and happiness) in each video frame. We then compared results across algorithms and across autism and control groups using robust non-parametric statistical tests.</p><p><strong>Results: </strong>There were significant differences in the performance of the three facial analysis algorithms including differences in the proportion of frames identified as containing a face and frames classified as containing each of the six examined facial expressions. Nevertheless, analyses across all three algorithms demonstrated that there were no significant differences in the quantity of any facial expression produced by children with autism and controls. Furthermore, the quantity of facial expressions did not correlate with autism symptom severity as measured by ADOS-2 CSS scores.</p><p><strong>Limitations: </strong>The current findings are limited to verbal children with autism who completed ADOS-2 assessments using modules 2 and 3 and were able to sit in a stable manner while facing a wall-mounted camera. Furthermore, the analyses focused on comparing the quantity of facial expressions across groups rather than their quality, timing, or social context.</p><p><strong>Conclusions: </strong>Commonly used automated facial analysis algorithms exhibit large variability in their output when identifying facial expressions of young children during naturalistic social interactions. Nonetheless, all three algorithms did not identify differences in the quantity of facial expressions across groups, suggesting that atypical production of facial expressions in verbal children with autism is likely related to their quality, timing, and social context rather than their quantity during natural social interaction.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"50"},"PeriodicalIF":5.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent aperiodic slope and alpha dynamics expose cortical excitability gradients in fragile X syndrome.","authors":"Rana Elmaghraby, Yanchen Liu, Priya Ramesh, Grace Westerkamp, Meredith A Nelson, Travis Larsh, Elizabeth Smith, Donald L Gilbert, Steve W Wu, Craig A Erickson, Ernest V Pedapati","doi":"10.1186/s13229-025-00682-0","DOIUrl":"10.1186/s13229-025-00682-0","url":null,"abstract":"<p><strong>Background: </strong>Fragile X syndrome (FXS) is characterized by cortical hyperexcitability, a core neurophysiological feature that contributes to sensory hypersensitivity, cognitive dysfunction, and other disabling symptoms. This disruption in excitatory-inhibitory balance is a key pharmacological target, yet reliable biomarkers to quantify it noninvasively remain limited. Spectral slope, derived from the aperiodic component of the EEG power spectrum, has emerged as a potential index of cortical excitability. Here, we evaluated spectral slope and theta-alpha peak frequency in individuals with FXS to assess their utility as candidate neurophysiological biomarkers.</p><p><strong>Methods: </strong>Five minutes of resting state EEG data were collected from 70 subjects with FXS (mean age 20.5 ± 10 years; 32 females) and 71 age-matched controls (mean age 22.2 ± 10.7 years; 30 females). The Spectral Parameterization toolbox (SpecParam) was used to separate periodic and aperiodic components of the source localized power spectra and characterize aperiodic slope and theta-alpha peak frequency.</p><p><strong>Results: </strong>Statistical modeling of aperiodic slope revealed a significant two-way interaction between sex and diagnostic group, but no interaction with brain lobe. Among males, the aperiodic slope was significantly decreased in FXS, indicating greater cortical excitability, compared to typically developing controls (TDC), whereas no difference was observed between FXS and TDC females. For peak alpha frequency, statistical modeling identified significant two-way interactions between sex and diagnostic group, and between brain lobe and diagnostic group, but no significant three-way interaction.</p><p><strong>Limitations: </strong>This study is limited by the absence of non-invasive measures of cortical fragile X mental retardation protein (FMRP). Additionally, participants were not stratified by mosaic status and FMRP levels were not quantified, which could affect variability and interpretation.</p><p><strong>Conclusion: </strong>Compared to traditional band-limited power measures, aperiodic slope provides a more direct and validated index of excitation-inhibition balance. Our findings of reduced aperiodic slope in male subjects with FXS align with preclinical circuit-level evidence of increased excitability in FXS and are consistent with previous findings of reduced individual alpha peak frequency, supporting with thalamocortical dysrhythmia models of FXS. Importantly, aperiodic slope measurements can be applied directly to various modalities of local field potential data, enabling more robust cross-species and translational comparisons.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"49"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different exploration strategies along the autism spectrum: diverging effects of autism diagnosis and autism traits.","authors":"Fien Goetmaeckers, Judith Goris, Jan R Wiersema, Tom Verguts, Senne Braem","doi":"10.1186/s13229-025-00679-9","DOIUrl":"10.1186/s13229-025-00679-9","url":null,"abstract":"<p><p>BACKGROUND: When faced with many options to choose from, humans typically need to explore the utility of new choice options. People with an autism diagnosis or elevated autism traits are thought to avoid exploring such unknown options, but it remains unclear how autism affects exploration in decision spaces with many options. METHODS: In a large online sample (N = 588), we investigated the impact of autism diagnosis or elevated autism traits on exploration behavior during value-based decision-making in vast decision spaces. We used a 121-armed bandit with spatially correlated choice options, and a dedicated computational model to disentangle generalization, uncertainty-guided exploration, and random exploration strategies. RESULTS: Our findings show that participants with a self-reported autism diagnosis were less likely to explore novel choice options and more likely to exploit known high-value options. Computational modeling suggests they engaged in less uncertainty-driven exploration but exhibited equal random exploration and generalization strategies. Interestingly, among non-diagnosed participants, people with elevated autism traits did not explore less. LIMITATIONS: This study relies on self-reported autism diagnoses and trait measures collected online. This may limit the generalizability of the findings to clinically verified or more diverse autism populations. CONCLUSIONS: Our findings highlight important differences in exploration strategies between clinical and subclinical populations and emphasize the importance of cognitive modeling and using vast decision spaces to better understand autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"47"},"PeriodicalIF":5.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autistic traits are associated with lower perceived executive function but not poorer executive function task performance in the general population: complementary meta-analytic evidence.","authors":"Michael K Yeung, Cassie T Y Li, Harris C W Chung, Tsz-Hei Au, Sin-Yue Lee, Jieru Bai","doi":"10.1186/s13229-025-00680-2","DOIUrl":"10.1186/s13229-025-00680-2","url":null,"abstract":"<p><strong>Background: </strong>Autistic individuals generally exhibit real-world executive function (EF) difficulties and perform poorly on EF tasks. However, while autistic traits are distributed continuously throughout the general population, the relationships between autistic traits and EF among nonclinical individuals remain unclear. Here, we conducted complementary meta-analyses to clarify the relationships between autistic traits and various aspects of EF in the general population.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, PsycINFO, and Web of Science on July 11, 2025. After screening by two independent reviewers, 39 articles that reported 40 studies were included. These studies either compared EF between groups with high and low autistic traits, based on a cutoff, or investigated the relationships between continuous measures of autistic traits and EF.</p><p><strong>Results: </strong>We found significant negative associations between autistic traits and EF among nonclinical individuals across EF processes. Notably, these relationships were observed only when EFs were measured using questionnaires rather than behavioral tasks. Specifically, random-effects and robust Bayesian meta-analyses revealed significant, strong correlations between higher autistic traits and poorer ratings on EF questionnaires, with primarily substantial evidence supporting the presence than absence of relationships. In contrast, the meta-analyses indicated nonsignificant, very weak correlations between higher autistic traits and poorer performances on EF tasks, with primarily substantial evidence supporting the absence than presence of relationships.</p><p><strong>Limitations: </strong>These findings were mainly based on self-reported measures of autistic traits in adults and derived from single studies without follow up or replication.</p><p><strong>Conclusions: </strong>Autistic traits are associated with lower perceived real-world EF behavior rather than poorer EF task performance in the general population. These findings underscore the importance of paying closer attention to addressing the concerns of individuals with high autistic traits and their parents regarding their own and their children's EF behavior. Based on the available evidence, we construct a picture of the relationships between autistic traits and EF across the trait's continuum.</p><p><strong>Registration: </strong>This study was preregistered at https://osf.io/zncv3 .</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"48"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcortical brain volume variations in autistic individuals across the lifespan.","authors":"Danielle Christensen, Young Seon Shin, Jingying Wang, Carolina R Cuomo, Tyler Dentry, Hanna M Gemmell, Stormi L Pulver, Ann-Marie Orlando, Walker S McKinney, Cassie J Stevens, Kathryn E Unruh, Bikram Karmakar, Stephen A Coombes, Matthew W Mosconi, Zheng Wang","doi":"10.1186/s13229-025-00673-1","DOIUrl":"10.1186/s13229-025-00673-1","url":null,"abstract":"<p><strong>Background: </strong>Structural alterations in subcortical brain regions-including the amygdala, hippocampus, basal ganglia, and cerebral ventricles-have been linked to various clinical features of autism spectrum disorder (ASD). However, volumetric features among these regions in autistic individuals across the lifespan remain poorly understood. This cross-sectional study aimed to investigate age-associated volumetric deviations in these clinically implicated subcortical regions of autistic individuals and neurotypical controls, and to examine the structural interrelationships within each group.</p><p><strong>Methods: </strong>We examined multi-site T1-weighted MRI data from 119 autistic and 122 neurotypical participants aged 7-73 years. Volumetric data for the amygdala, hippocampus, basal ganglia, and cerebral ventricles were harmonized across sites using the ComBat algorithm. Following this, volumetric composite indices (principal component scores) were extracted for each region using principal component analysis. These scores represent dominant volumetric patterns of each subcortical region, with higher values reflecting greater volume. These composite scores were then compared between groups and with increasing age.</p><p><strong>Results: </strong>Autistic participants exhibited greater amygdala volume in early life, followed by more pronounced age-associated reductions in adulthood compared to neurotypical controls. A similar trend was observed for the hippocampus, with early volumetric enlargement giving way to steeper declines in later years. In contrast, the autistic group consistently trended towards larger basal ganglia across the lifespan. Additionally, autistic participants showed accelerated enlargement in the cerebral ventricles with increasing age. Both groups exhibited patterns of inverse volumetric associations between the cerebral ventricles and surrounding subcortical regions in later adulthood; however, these relationships were more pronounced and widely distributed in the autistic group.</p><p><strong>Limitations: </strong>The cross-sectional design of this study limited us from capturing intra-individual differences at baseline and quantifying the lifespan trajectories of each participant. Site-related sampling differences may have introduced cohort bias in the results.</p><p><strong>Conclusions: </strong>Autistic participants and neurotypical controls exhibit distinct, age-related volumetric patterns across key subcortical brain regions. Enlargement of the cerebral ventricles and their inverse structural relationships with neighboring structures in later life may indicate atrophic processes beginning in middle adulthood in ASD. These findings highlight the need to further investigate mechanisms of atypical brain aging in ASD and consider these subcortical brain regions as potential biomarkers of neurodegeneration and intervention targets across the adult lifespan.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"46"},"PeriodicalIF":5.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postural sway dynamics in adults across the autism spectrum: a multifactor approach.","authors":"Bess F Bloomer, Amanda R Bolbecker, Emily L Gildea, Daniel P Kennedy, Krista M Wisner, Brian F O'Donnell, William P Hetrick","doi":"10.1186/s13229-025-00676-y","DOIUrl":"10.1186/s13229-025-00676-y","url":null,"abstract":"<p><p>BACKGROUND: Motor challenges are highly prevalent within autism, and increased postural sway has been consistently demonstrated in autistic youth. However, the extent to which sway anomalies extend into adulthood remains understudied. This study aimed to investigate whether increased postural sway is altered in autistic adults compared to neurotypical controls using established sway metrics including sway area and path, as well as rambling-trembling decomposition—an approach that differentiates the postural sway signal into central and peripheral nervous system components. METHODS: 49 adults with autism spectrum conditions (ASC) and 94 neurotypical controls (NC) participated in a postural sway task on a force platform with manipulations of visual input and stance width. Traditional geometric methods (sway area and path), the spatial characteristics of the body’s adjustment to maintain balance, were measured. As resulting sway measures often covary, multiple factor analysis (MFA) was applied to reduce the measures into distinct, non-redundant dimensions that simplified the data. Group comparisons were completed across these different levels of analysis. RESULTS: We observed increased sway path and medio-lateral trembling in ASC compared to NC (p < 0.05). Significant group by vision interactions revealed that ASC sway increases were more apparent in eyes-open conditions for sway area and rambling and trembling in the anterior-posterior plane (p < 0.01), possibly suggesting differential sensory reweighting of visual input by ASC, or difficulties with multisensory integration. MFA revealed two key dimensions. A fast frequency dimension, linked to peripheral processes, explained most of the overall variance (62.9%) and captured more variance in the ASC group than in NC. A slower frequency dimension, linked to central processes, explained 8.0% of the variance. LIMITATIONS: Order of sway conditions was consistent among all participants, so it is possible that participant fatigue influenced later sway conditions. CONCLUSIONS: Building upon previous research finding increased postural sway in autism, we found that combining multiple approaches collectively suggest the critical role of peripheral contributions and visual input in postural sway in autism. Fast-frequency processes that are peripherally-driven may be of particular importance in sway in autistic adults, and should be prioritized in future research to better understand balance performance in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"44"},"PeriodicalIF":5.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}