Molecular Autism最新文献

{"title":"Who benefits most? A randomized controlled trial for Parent-implemented social communication intervention for chinese-speaking autistic preschoolers.","authors":"Li Wang, Yujia Shi, Hon-Cheong So, Hoyee W Hirai, Xin Qi, Carol K S To, Florrie Fei-Yin Ng, Patrick C M Wong","doi":"10.1186/s13229-026-00725-0","DOIUrl":"10.1186/s13229-026-00725-0","url":null,"abstract":"<p><strong>Background: </strong>Parent-implemented interventions (PIIs) are well established for improving developmental outcomes in autistic children. As evidence has accumulated, the field has increasingly shifted toward understanding for whom, and through which delivery formats PIIs can be most effectively implemented. These questions are pressing in non-Western contexts, where access to professional services is limited and culturally appropriate interventions are needed. This RCT, one of the largest of its kind in China, addressed this gap by comparing two scalable delivery formats (speech-language therapist [SLT]-led online groups vs. flexible Self-study format) of a culturally adapted social communication program and examining differential intervention responses and sustained engagement.</p><p><strong>Methods: </strong>A total of 112 Chinese-speaking autistic children aged 24-60 months with limited spontaneous expressive language were randomized to a 20-week SLT-led or Self-study intervention. Autism severity, social functioning, and language skills were assessed at baseline, post-intervention, and 12 months after baseline. Parental stress, parenting sense of competence, and strategy use were also measured. Child, parent, and family baseline characteristics predicting differential outcomes and engagement were examined.</p><p><strong>Results: </strong>No consistent differences between delivery formats were observed across most outcomes. Children's social functioning, expressive and receptive language showed improvement, and parental self-efficacy increased while stress decreased in both formats. Individualized analyses indicated greater benefits of the SLT-led format for children from lower-income families and those with greater developmental needs, whereas families with stronger baseline functioning showed comparable gains in the Self-study format. Attrition was higher in the Self-study format and was associated with lower child social skills and receptive languages, along with lower parental use of engagement-promoting behaviors and lower broader autism-related traits.</p><p><strong>Limitations: </strong>Despite being one of the largest RCTs of its kind in China, the study may have been underpowered to detect small between-format differences, and the relatively modest sample size for the individualized machine-learning analyses limits the interpretation of these exploratory findings. Parental strategy use was measured using a general interaction coding scheme rather than intervention-specific behaviors. Higher attrition in the Self-study format warrants cautious interpretation, although sensitivity analyses supported the robustness of findings.</p><p><strong>Conclusions: </strong>This study provides evidence supporting a culturally grounded PII associated with improvements in social functioning and language outcomes in autistic preschoolers, alongside increases in parental self-efficacy and reductions in parenting stress. Although no consi","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13335151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376111","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":"Autism in neurofibromatosis type 1: prevalence, phenotype and clinical implications.","authors":"Jonathan M Payne, Kristina M Haebich, Anita K Chisholm, Karin S Walsh, Francesca Lami, Alexandra Ure, Tiba Maloof, Amanda Brignell, Stephen J C Hearps, Alice Maier, Hayley Darke, Yael Rothman, Srishti Rau, Belinda Barton, Rena Shrestha, Renee Pascouau, Natasha L Hogan, Yu Fan Eng, Gabriel Dabscheck, Vicki A Anderson, David Coghill, Kathryn N North, Natalie A Pride","doi":"10.1186/s13229-026-00726-z","DOIUrl":"10.1186/s13229-026-00726-z","url":null,"abstract":"<p><strong>Background: </strong>Monogenic conditions, such as neurofibromatosis type 1 (NF1), provide a unique opportunity to study autism within a known molecular pathway. This study estimated the prevalence of autism in a large international NF1 cohort and examined how autistic traits relate to cognitive, behavioral, and adaptive functioning.</p><p><strong>Methods: </strong>In this cross-sectional study, 202 children with NF1 and 106 typically developing controls (aged 3-15 years) completed standardized cognitive testing and parent-reported behavioral measures. NF1 participants scoring ≥ 60 on the Social Responsiveness Scale-2 were evaluated using the Autism Diagnostic Observation Schedule-2 and Autism Diagnostic Interview-Revised, with DSM-5-TR autism diagnoses established by multidisciplinary consensus. Neurodevelopmental profiles were compared across NF1 subgroups (autism, broader autistic traits, no-autistic-traits) and controls.</p><p><strong>Results: </strong>Autistic traits were elevated and continuously distributed in NF1. An estimated 28% (95%CI: 21.7%-34.3%) met DSM-5-TR criteria for autism and 22% exhibited a broader autistic phenotype, with comparable rates in males and females. Children classified as autistic and those with broader autistic traits showed similarly marked behavioral and adaptive challenges, whereas NF1 children without autistic traits showed milder difficulties. Findings establish NF1 as a condition in which autism is common and clinically significant. Autistic features in NF1 occur across the cognitive spectrum and are accompanied by overlapping behavioral and functional impairments that challenge categorical diagnostic boundaries.</p><p><strong>Limitations: </strong>The cross-sectional design precludes conclusions about developmental trajectories. The absence of genotype data prevented exploration of genotype-phenotype correlations and the influence of polygenic risk factors outside the NF1 locus.</p><p><strong>Conclusions: </strong>Findings provide strong support for routine, early screening for autism in NF1 and the recognition that subthreshold traits can be similarly impairing. NF1 provides a powerful model for investigating how a monogenic condition contributes to diverse neurodevelopmental profiles and informs precision-medicine approaches in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369034","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":"Developing a consensus research definition for profound autism using a modified Delphi method.","authors":"Matthew Siegel, Catherine L Lord, Helen Tager-Flusberg, Judith Ursitti, Alycia Halladay, Alison T Singer","doi":"10.1186/s13229-026-00727-y","DOIUrl":"10.1186/s13229-026-00727-y","url":null,"abstract":"<p><strong>Background: </strong>The diagnostic term, autism spectrum disorder, encompasses the full range of impairments associated with the autism spectrum, a significant change from earlier DSM definitions that identified various subtypes of autism. However, the majority of autism-related research and cultural representations in recent years has focused on autistic individuals with strong language and cognitive abilities. In 2021, the administrative term Profound Autism (PA) was proposed by a Lancet Commission to draw attention to autistic people whose impairments require lifelong, round-the-clock care. The initial definition of PA included a minimum age and requiring 24/7 access to an adult to ensure safety, and suggested considering IQ, and verbal ability when defining this group. However, researchers have subsequently utilized widely varying criteria in studies of this group, producing results that are difficult to compare and limit the potential for the identification of this group to advance knowledge about their strengths and needs.</p><p><strong>Methods: </strong>To address the need for studies that use comparable samples and increase clarity in communication and interpretation of results, we carried out a systematic, multi-stage Delphi consensus study with over 70 participants who identified as researchers, caregivers, autistic individuals, and clinicians, to measure consensus on components of a research definition of PA. A series of questions was developed for the primary domains of interest.</p><p><strong>Results: </strong>After two rounds of review and voting, 76% of the respondents agreed on a research definition of PA of: adaptive functioning well below age level, requiring adult supervision to ensure physical and mental health, safety and well-being, being at least 8 years old, diagnosed with ASD, and having severely impaired cognitive abilities (reflected by IQ score below 50) and/or not verbally communicating other than single words or fixed phrases used predominantly to have their basic needs met.</p><p><strong>Limitations: </strong>Variations in access to measurement tools, as well as access to services across the world, limit the utility of this definition outside research practices, and a response rate of 58% yielded a final round sample size of 78 that may underrepresent portions of the stakeholder community and was overwhelmingly composed of respondents from the United States.</p><p><strong>Conclusions: </strong>Based on these findings, a new working research definition of profound autism is proposed. Adoption of this definition could improve comparability across research studies, enhance the impact and generalizability of results, and better target interventions and supports for this high-needs group.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361386","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":"Nuances of double empathy in autistic and non-autistic people: examination using the empathic accuracy paradigm.","authors":"Yonat Rum, Noa Feldman, Shir Genzer, Carrie Allison, Ofer Golan, Anat Perry, Simon Baron-Cohen","doi":"10.1186/s13229-026-00723-2","DOIUrl":"10.1186/s13229-026-00723-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Social communication difficulties in autism were traditionally attributed to deficits in empathy, that is, understanding others' mental states and responding to these with a similar or appropriate emotion, within autistic individuals. The double empathy problem theory proposes that difficulties with cross-neurotype empathy are bidirectional. This study examines predictions from the double empathy problem theory, mainly whether autistic and non-autistic individuals differ in their empathy towards autistic versus non-autistic social targets, using an empathic accuracy paradigm alongside self-report measures of empathy and empathic interest.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A novel empathic accuracy stimulus featuring video-recorded autobiographical stories from five autistic and five non-autistic adult storytellers was used. Participants [141 autistic, 94 non-autistic; mean age: 49.09 years (SD = 16.41)] were recruited through the Cambridge Autism Research Database. Each participant viewed two stories (one autistic, one non-autistic storyteller) in a randomized design, continuously rated storytellers' emotional valence, and globally rated the degree to which they believed the storytellers felt each of 12 discrete emotions. Accuracy was computed as concordance with storytellers' own ratings. Participants also self-reported empathy and empathic interest toward the storyteller in the target videos. Mixed linear models examined the effects of rater neurotype, target neurotype, and their interaction. Participants' text responses were qualitatively analyzed using an inductive, data-driven approach to identify patterns within the data, which converged into subthemes and themes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;No significant main effects emerged for rater or target neurotype on continuous valence or specific emotions' empathic accuracy. A trend-level interaction (p=.059, d = 0.13) suggested that autistic raters showed relatively higher continuous valence empathic accuracy toward autistic targets than non-autistic raters. Non-autistic raters reported significantly higher self-reported empathy (p&lt;.001, d=-0.67) and empathic interest (p&lt;.001, d=-0.43) regardless of target neurotype. Qualitative analysis revealed that autistic participants described difficulties in identifying emotions and in performing the EA task, and engaged in metacognitive introspection, while non-autistic participants focused more on task design feedback.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations: &lt;/strong&gt;The use of video-based experimental design may not fully capture the complexity of spontaneous social encounters. The self-selected sample of autistic participants may not represent the full autism spectrum or include individuals requiring greater support, potentially affecting generalizability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Findings suggest partial support for the double empathy problem theory and potential underestimation of autistic participants of their own emp","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218485","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":"A transdiagnostic AI-based measure of interpersonal coordination in autism and other conditions.","authors":"Lisa D Yankowitz, Casey J Zampella, Juhi Pandey, G Keith Bartley, Julia Parish-Morris, Edward S Brodkin, John D Herrington, Birkan Tunç, Robert T Schultz, Evangelos Sariyanidi","doi":"10.1186/s13229-026-00722-3","DOIUrl":"10.1186/s13229-026-00722-3","url":null,"abstract":"<p><strong>Background: </strong>Interpersonal coordination is a fundamental social behavior that has been shown to be reduced in autism, though less is known about other psychiatric conditions. An automated quantitative measure of interpersonal coordination would enhance assessment, diagnosis, and monitoring of treatment-related change in autism and other psychiatric conditions. We introduce and apply a novel AI-based measure ('concurrence') to quantify and compare nonverbal interpersonal coordination during naturalistic conversation in individuals with and without various psychiatric presentations.</p><p><strong>Methods: </strong>The primary analysis included 380 12-18-year-olds with neurotypical development (NT), autism (AUT), or other psychiatric conditions (PSY), recorded during videoconference get-to-know-you conversations with a research staff member ('partner'). Replication analyses included 72 12-18-year-olds with NT or AUT, recorded during face-to-face conversations. A self-supervised AI method (concurrence) was applied to time series data representing facial expressions and head movements of participants and their conversation partners. This yielded interpersonal coordination scores for all participant-partner dyads, which were then compared transdiagnostically. Convergent and discriminant validity were assessed using annotated subsamples from a combined sample of 609 5-52-year-olds. Convergent validity was assessed with measures of social gaze, motor imitation ability, and conversation quality; discriminant validity was assessed with IQ scores.</p><p><strong>Results: </strong>In the videoconference sample, AUT demonstrated significantly lower interpersonal coordination than PSY (unadjusted Cohen's d = 0.46, p < 0.001) and NT (d = 1.03, p < 0.001), with PSY also lower than NT (d = 0.50, p < 0.001). The AUT < NT effect was replicated in the face-to-face sample (d = 0.73, p < 0.05). The group-by-context interaction was nonsignificant (p = 0.33), suggesting group differences are robust to recording context. Convergent and discriminant validity was demonstrated through positive associations between interpersonal coordination and mutual social gaze (r(108) = 0.46, p < 0.0001), gross motor imitation ability (r(35) = 0.41, p < 0.05), and conversation quality ratings (r(364) = 0.34, p < 0.0001), but not IQ (r(367) = 0.03, p = 0.55).</p><p><strong>Limitations: </strong>Generalizability is limited by sample characteristics including cognitive and verbal ability, age, and sex.</p><p><strong>Conclusions: </strong>The study demonstrates reduced interpersonal coordination in adolescents with autism and other psychiatric conditions (AUT<PSY<NT) using a novel, transdiagnostic computational measure. This finding replicated across different conversational contexts and the concurrence measure demonstrated convergent and discriminant validity, highlighting its potential as an automated and scalable individual-level measure of social skills.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055882","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":"From cognitive abstraction to adaptive behavior: neural bases of concept learning in autistic adolescents.","authors":"Yijun Chen, Brylee Hawkins, Hannah Puckett, Kat Sharp, Andrea Lopez, Dagmar Zeithamova, Hua Xie, Alyssa Verbalis, Ashley S VanMeter, William D Gaillard, Lauren Kenworthy, Chandan J Vaidya","doi":"10.1186/s13229-026-00721-4","DOIUrl":"10.1186/s13229-026-00721-4","url":null,"abstract":"<p><strong>Background: </strong>Learned knowledge does not consistently generalize to new contexts in autistic individuals, limiting potential for adapting to real-world demands. This challenge is hypothesized to stem from difficulties with forming abstract representations, potentially arising from perceptual processing that favors local details over the gestalt. We tested the prediction that generalization would be primarily based on exemplar-specific representations in autistic youth using computational modelling coupled with neuroimaging.</p><p><strong>Methods: </strong>Sixty-four autistic adolescents without intellectual disability (69% males; ages 14-18 years) completed a category generalization task during functional magnetic resonance imaging at two time points. Computational models estimated abstract (prototype-based) and specific (exemplar-based) representations and underlying neural correlates. We further examined associations with adaptive functioning and moderation by autistic traits.</p><p><strong>Results: </strong>Contrary to predictions, we observed a consistent prototype-dominant majority, a subgroup who generalized without consistent representational reliance, and a small minority who failed to acquire category structure. Neural prototype correlates were observed in bilateral ventromedial prefrontal cortex (VMPFC), inferior parietal lobule (IPL), right frontal pole, and right lateral occipital cortex, while neural exemplar correlates were observed in bilateral cuneus. Better generalization predicted better real-world adaptive functioning. Moreover, greater prototype-related activation in left IPL predicted better adaptive functioning in participants with higher autistic traits.</p><p><strong>Limitations: </strong>Generalizability is limited to autistic adolescents without intellectual disability as the design did not include typically developing youth.</p><p><strong>Conclusions: </strong>These findings challenge the prevailing view that concept learning in autism relies primarily on hyper-specific perceptual processing, identify meaningful variability in representational strategies, and reveal neural pathways through which abstract representation may support real-world adaptive behavior. These findings set the foundation for exploring abstract representation as an intervention target in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005831","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":"JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder.","authors":"Qi Wang, Huamin Yin, Qi Jiang, Yubo Qi, Jieli Bai, Zhendong Wang, Kailai Liu, Ruizhen Sun, Wenhang Wang, Canying Liu, Weishuo Yan, Jin Luo, Lian Duan, Zhiyan Shan","doi":"10.1186/s13229-026-00717-0","DOIUrl":"10.1186/s13229-026-00717-0","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated stress responses are increasingly implicated in the pathophysiology of autism spectrum disorder (ASD). Astrocytes, which are highly vulnerable to stress, critically support neuronal survival; however, their specific role in ASD remains poorly defined.</p><p><strong>Methods: </strong>We analyzed single nucleus RNA sequencing data from postmortem cortices of ASD and control donors. Our analysis included enrichment analysis of astrocyte subpopulations and integrated pySCENIC-based GRN reconstruction, TF profiling, regulon-DEG analysis, and cell-cell communication. Mechanistic studies involved human iPSC-derived astrocytes-neurons co-culture and astrocyte-specific JUND overexpression in mice. Functional and behavioral assessments were performed to evaluate neuronal viability and ASD-relevant phenotypes.</p><p><strong>Results: </strong>A subpopulation of stress-responsive astrocytes (SRAs) was identified as specifically enriched in ASD, displaying early transcriptional activation and increased abundance. These SRAs showed marked upregulation of both stress-response pathways and distinct reactive signatures. JUND was established as the core transcriptional orchestrator, controlling 23.8% of the dysregulated transcriptome that defines the core stress-responsive signature, including multiple ASD risk genes. JUND overexpression in astrocytes recapitulated the SRAs molecular profile, while astrocyte-specific JUND activation in mouse cortex elicited core ASD-like behaviors. Mechanistically, JUND upregulated the gap junction gene GJA1, enhancing astrocyte-neuron communication and promoting neuronal apoptosis. This pathogenic cascade was rescued by the gap junction inhibitor GAP27.</p><p><strong>Limitations: </strong>This study is focused solely on specific brain regions, the generalizability of the JUND-GJA1-GAP axis across diverse ASD subtypes remains to be validated, and the complete activation pathway of JUND signaling within SRAs as well as their interaction mechanisms with other glial cells are not well understood.</p><p><strong>Conclusions: </strong>Our findings demonstrate that a specialized astrocyte subpopulation mediates stress-induced dysfunction in ASD via a JUND-GJA1-GAP apoptotic signaling axis, providing a translational anchor for targeting astrocyte-specific pathways in ASD therapy.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973879","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":"Subclinical neuropsychiatric trait variation in parents of children with autism spectrum disorder: a cohort study.","authors":"Lindsay J Mullin, Kai Xia, Jeffrey Wang, Chimei M Lee, Tessa G Buscher, Carolyn Lasch, Catherine A Burrows, Jed T Elison, Mark D Shen, Steven R Dager, Annette M Estes, Heather C Hazlett, Natasha Marrus, Juhi Pandey, Robert T Schultz, Tanya St John, Lonnie Zwaigenbaum, John N Constantino, Joseph Piven, Jessica B Girault","doi":"10.1186/s13229-026-00720-5","DOIUrl":"10.1186/s13229-026-00720-5","url":null,"abstract":"<p><strong>Background: </strong>Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism.</p><p><strong>Methods: </strong>Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were compared across groups using analysis of variance. Between-parent and within-parent correlations across trait domains examined patterns of familial trait aggregation and assessed shared versus unique contributions to the inheritance of autism. Logistic regression assessed the predictive utility of parental traits for simplex vs. multiplex group membership.</p><p><strong>Results: </strong>Mean levels of paternal autistic traits (F(2, 224) = 5.67, FDR-adjusted p-value (q) = 0.013) and maternal anxious (F(2, 262) = 11.14, q < 0.001) and depressive (F(2, 262) = 7.08, q = 0.005) traits differed between groups. Post-hoc tests revealed elevated autistic traits in multiplex fathers (q = 0.009) and elevated anxious (q < 0.001) and depressive (q = 0.004) traits in multiplex mothers compared to parents of non-autistic children; simplex parents did not differ from either of the other groups. Parental traits jointly accounted for 7.9% of autism recurrence liability in multiplex families. Elevations in autistic traits co-occur with elevations in neuropsychiatric traits in simplex parents (0.35 ≤ r ≤ 0.43) but were uncorrelated in multiplex parents.</p><p><strong>Limitations: </strong>Findings from this study may not generalize to more heterogeneous samples with differing racial, ethnic, and socioeconomic demographics. Exclusionary criteria for the original study may result in families with a lower trait burden for psychiatric disorders than the broader population of parents of autistic children.</p><p><strong>Conclusions: </strong>Results highlight unique patterns of autistic, anxious, and depressive trait presentation and aggregation in multiplex parents. Findings call for a transdiagnostic approach to quantifying genetic liability in families with autistic children.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948363","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":"Mapping sensory sensitivity in autism.","authors":"Bat-Sheva Hadad, Inbar Leon, Marissa Hartston, Erez Freud, Ahmad Abu-Akel","doi":"10.1186/s13229-026-00719-y","DOIUrl":"10.1186/s13229-026-00719-y","url":null,"abstract":"<p><strong>Background: </strong>Sensory perception in autism is strikingly heterogeneous, with individuals showing both hypo- and hypersensitivity across different sensory domains. While sensory differences are widely recognized as a core feature of autism, the structure and underlying patterns of this variability remain poorly understood. Previous studies have yielded mixed findings, often examining sensory processing in isolation within single domains, thereby limiting a comprehensive understanding of sensory sensitivity in autism.</p><p><strong>Methods: </strong>We compiled psychophysical data from 107 autistic and 408 age- and IQ-matched non-autistic individuals across 32 experimental conditions spanning multiple perceptual domains, including size, brightness, orientation, pitch, and face processing. Two complementary statistical approaches were used: segmented regression and a Bayesian hierarchical model.</p><p><strong>Results: </strong>Despite substantial inter- and intra-individual variability, both models revealed a consistent domain-specific pattern: on average, autistic individuals showed reduced sensitivity to faces and speech, while performance on basic non-social tasks was comparable to or exceeded that of the comparison group. Bayesian modelling further indicated that social relevance, rather than domain alone, accounted for the primary source of divergence between groups.</p><p><strong>Limitations: </strong>This study focused on sensory sensitivity thresholds and did not assess perceptual biases or changes in subjective appearance of the stimuli. A full account of perception in autism requires considering these broader alterations.</p><p><strong>Conclusions: </strong>The current findings suggest that sensory differences in autism reflect a structured perceptual profile shaped by social relevance, stimulus complexity, and individual variability. The results highlight the importance of individualized sensory profiling and may inform both theoretical models and personalized approaches to intervention in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941449","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":"Advantages of combining multiple eye-tracking paradigms for distinguishing young autistic from non-autistic children.","authors":"Dan Xu, Lan Zhang, Xiangqin Wang, Xun Zeng, Linghong Huang, Yanan Qing, Menghan Zhou, Qin Li, Xiaojiao Yang, Weihua Zhao, Shuxia Yao, Jiao Le, Keith M Kendrick","doi":"10.1186/s13229-026-00718-z","DOIUrl":"10.1186/s13229-026-00718-z","url":null,"abstract":"<p><strong>Background: </strong>Single-paradigm, single-measure eye-tracking protocols have demonstrated utility in distinguishing between autistic and non-autistic children although effect sizes and reproducibility vary. There is a need for brief, scalable digital behavioral biomarkers that integrate complementary information from multiple eye-tracking paradigms and achieve improved accuracy in combination.</p><p><strong>Methods: </strong>74 autistic and 63 non-autistic children aged 24-72 months performed five different eye-tracking paradigms (facial emotion processing, gaze-following, dynamic social versus geometric patterns, social interaction, and spinning) lasting 3.25 min in hospital or kindergarten settings. A broad set of fixation-based metrics was extracted from each paradigm. We compared discrimination performance of single-paradigm models versus a combined multi-paradigm model using random forest (RF) classifiers. In the autistic group, symptom severity was assessed using standardized clinical measures. We further evaluated whether paradigms contributed complementary information, estimated potential clinical value of multi-paradigm models, and conducted exploratory subgrouping analyses to examine whether eye-tracking-defined profiles aligned with symptom-based groupings.</p><p><strong>Results: </strong>All individual paradigms distinguished between autistic and non-autistic children, but RF models found a combined paradigm-based model performed best, achieving an AUC of 95% and an accuracy of 90%. Representational similarity analysis indicated that paradigms contributed partially distinct information rather than reflecting a single redundant dimension of social attention. Decision curve analysis demonstrated that the multi-paradigm model provided added net benefit across clinically relevant threshold probabilities compared with strategies based on treating all or no children as autistic. Clustering of eye-tracking features revealed three autistic subgroups with distinct visual preference profiles, whereas clustering based on clinical symptoms alone identified only two subgroups.</p><p><strong>Limitations: </strong>Sex imbalance and group differences in developmental quotient may have confounded some effects. Models were only internally cross-validated in a single cohort and decision curve analysis relied on assumed clinic prevalence, so external validation and testing in larger, more diverse and high-risk samples, including other neurodevelopmental conditions, are needed.</p><p><strong>Conclusions: </strong>A brief multi-paradigm eye-tracking battery yields robust case-control discrimination and non-redundant behavioral readouts, suggesting that it may complement symptom-based approaches and provide a scalable behavioral framework for future studies seeking to bridge molecular findings with observable autistic profiles.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817697","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}