Molecular Autism最新文献

{"title":"Mate selection and current trends in the prevalence of autism.","authors":"Elizabeth Forsen, Natasha Marrus, Jacqueline Joyce, Yi Zhang, John N Constantino","doi":"10.1186/s13229-024-00607-3","DOIUrl":"10.1186/s13229-024-00607-3","url":null,"abstract":"<p><strong>Background: </strong>According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children.</p><p><strong>Methods: </strong>Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2).</p><p><strong>Results: </strong>We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30).</p><p><strong>Limitations: </strong>The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report.</p><p><strong>Conclusion: </strong>Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"29"},"PeriodicalIF":6.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627181","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":"Phenotypic and ancestry-related assortative mating in autism.","authors":"Jing Zhang, J Dylan Weissenkampen, Rachel L Kember, Jakob Grove, Anders D Børglum, Elise B Robinson, Edward S Brodkin, Laura Almasy, Maja Bucan, Ronnie Sebro","doi":"10.1186/s13229-024-00605-5","DOIUrl":"10.1186/s13229-024-00605-5","url":null,"abstract":"<p><strong>Background: </strong>Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.</p><p><strong>Methods: </strong>To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).</p><p><strong>Results: </strong>We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D² on the order of 1 × 10^-5).</p><p><strong>Limitations: </strong>We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.</p><p><strong>Conclusions: </strong>This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"27"},"PeriodicalIF":6.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321165","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":"Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder.","authors":"Laura Simões de Oliveira, Heather E O'Leary, Sarfaraz Nawaz, Rita Loureiro, Elizabeth C Davenport, Paul Baxter, Susana R Louros, Owen Dando, Emma Perkins, Julien Peltier, Matthias Trost, Emily K Osterweil, Giles E Hardingham, Michael A Cousin, Sumantra Chattarji, Sam A Booker, Tim A Benke, David J A Wyllie, Peter C Kind","doi":"10.1186/s13229-024-00601-9","DOIUrl":"10.1186/s13229-024-00601-9","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5^-/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5^-/y rats.</p><p><strong>Methods: </strong>To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology.</p><p><strong>Results: </strong>Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5^-/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca²⁺ permeable AMPA receptor mediated currents are unchanged in Cdkl5^-/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses.</p><p><strong>Conclusions: </strong>Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity.</p><p><strong>Limitations: </strong>This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"28"},"PeriodicalIF":6.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321164","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":"Enhanced interest in letters and numbers in autistic children.","authors":"Alexia Ostrolenk, David Gagnon, Mélanie Boisvert, Océane Lemire, Sophie-Catherine Dick, Marie-Pier Côté, Laurent Mottron","doi":"10.1186/s13229-024-00606-4","DOIUrl":"10.1186/s13229-024-00606-4","url":null,"abstract":"<p><strong>Background: </strong>An intense and precocious interest in written material, together with a discrepancy between decoding and reading comprehension skills are defining criteria for hyperlexia, which is found in up to 20% of autistic individuals. It may represent the extreme end of a broader interest in written material in autism. This study examines the magnitude and nature of the interest in written material in a large population of autistic and non-autistic children.</p><p><strong>Methods: </strong>All 701 children (391 autistic, 310 non-autistic) under the age of 7 referred to an autism assessment clinic over a span of 4 years were included. Ordinal logistic regressions assessed the association between diagnosis and the level of interest in letters and numbers. A nested sample of parents of 138 autistic, 99 non-autistic clinical, and 76 typically developing (TD) children completed a detailed questionnaire. Cox proportional hazards models analyzed the age of emergence of these interests. Linear regressions evaluated the association between diagnosis and interest level. The frequency of each behaviour showing interest and competence with letters and numbers were compared.</p><p><strong>Results: </strong>In the two studies, 22 to 37% of autistic children had an intense or exclusive interest in letters. The odds of having a greater interest in letters was 2.78 times higher for autistic children than for non-autistic clinical children of the same age, and 3.49 times higher for the interest in numbers, even if 76% of autistic children were minimally or non-verbal. The age of emergence of these interests did not differ between autistic and TD children and did not depend on their level of oral language. Non-autistic children showed more interest in letters within a social context.</p><p><strong>Limitations: </strong>The study holds limitations inherent to the use of a phone questionnaire with caregivers and missing sociodemographic information.</p><p><strong>Conclusions: </strong>The emergence of the interest of autistic children toward written language is contemporaneous to the moment in their development where they display a strong deficit in oral language. Together with recent demonstrations of non-social development of oral language in some autistic children, precocious and intense interest in written material suggests that language acquisition in autism may follow an alternative developmental pathway.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"26"},"PeriodicalIF":6.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311080","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":"Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.","authors":"Laura Hegemann, Elizabeth C Corfield, Adrian Dahl Askelund, Andrea G Allegrini, Ragna Bugge Askeland, Angelica Ronald, Helga Ask, Beate St Pourcain, Ole A Andreassen, Laurie J Hannigan, Alexandra Havdahl","doi":"10.1186/s13229-024-00599-0","DOIUrl":"10.1186/s13229-024-00599-0","url":null,"abstract":"<p><strong>Background: </strong>Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations.</p><p><strong>Methods: </strong>In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests.</p><p><strong>Results: </strong>We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r_g range = - 0.27-0.78), ADHD (items r_g range = - 0.40-1), and schizophrenia (items r_g range = - 0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other.</p><p><strong>Conclusions: </strong>These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"25"},"PeriodicalIF":6.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288323","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":"Measuring self and informant perspectives of Restricted and Repetitive Behaviours (RRBs): psychometric evaluation of the Repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settgs.","authors":"Catherine R G Jones, Lucy A Livingston, Christine Fretwell, Mirko Uljarević, Sarah J Carrington, Punit Shah, Susan R Leekam","doi":"10.1186/s13229-024-00603-7","DOIUrl":"10.1186/s13229-024-00603-7","url":null,"abstract":"<p><strong>Background: </strong>Brief questionnaires that comprehensively capture key restricted and repetitive behaviours (RRBs) across different informants have potential to support autism diagnostic services. We tested the psychometric properties of the 20-item Repetitive Behaviours Questionnaire-3 (RBQ-3), a questionnaire that includes self-report and informant-report versions enabling use across the lifespan.</p><p><strong>Method: </strong>In Study 1, adults referred to a specialised adult autism diagnostic service (N = 110) completed the RBQ-3 self-report version, and a relative or long-term friend completed the RBQ-3 informant-report version. Clinicians completed the abbreviated version of the Diagnostic Interview for Social and Communication Disorders (DISCO-Abbreviated) with the same adults as part of the diagnostic process. For half of the assessments, clinicians were blind to the RBQ-3 ratings. We tested internal consistency, cross-informant reliability and convergent validity of the RBQ-3. In Study 2, a follow-up online study with autistic (N = 151) and non-autistic (N = 151) adults, we further tested internal consistency of the RBQ-3 self-report version. We also tested group differences and response patterns in this sample.</p><p><strong>Results: </strong>Study 1 showed good to excellent internal consistency for both self- and informant-report versions of the RBQ-3 (total score, α = 0.90, ω = 0.90, subscales, α = 0.76-0.89, ω = 0.77-0.88). Study 1 also showed cross-informant reliability as the RBQ-3 self-report scores significantly correlated with RBQ-3 informant-report scores for the total score (r^s = 0.71) and subscales (r^s= 0.69-0.72). Convergent validity was found for both self and informant versions of the RBQ-3, which significantly correlated with DISCO-Abbreviated RRB domain scores (r^s = 0.45-0.54). Moreover, the RBQ-3 scores showed significantly weaker association with DISCO -Abbreviated scores for the Social Communication domain, demonstrating divergent validity. Importantly, these patterns of validity were found even when clinicians were blind to RBQ-3 items. In Study 2, for both autistic and non-autistic groups, internal consistency was found for the total score (α = 0.82-0.89, ω = 0.81-0.81) and for subscales (α = 0.68-0.85, ω = 0.69-0.85). A group difference was found between groups.</p><p><strong>Limitations: </strong>Due to the characteristics and scope of the specialist autism diagnostic service, further testing is needed to include representative samples of age (including children) and intellectual ability, and those with a non-autistic diagnostic outcome.</p><p><strong>Conclusions: </strong>The RBQ-3 is a questionnaire of RRBs that can be used across the lifespan. The current study tested its psychometric properties with autistic adults without intellectual disability and supported its utility for both clinical diagnostic and research settings.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"24"},"PeriodicalIF":6.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284245","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":"Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning.","authors":"Jaana Van Overwalle, Birte Geusens, Stephanie Van der Donck, Bart Boets, Johan Wagemans","doi":"10.1186/s13229-024-00604-6","DOIUrl":"10.1186/s13229-024-00604-6","url":null,"abstract":"<p><strong>Background: </strong>Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization.</p><p><strong>Methods: </strong>The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures.</p><p><strong>Results: </strong>Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results.</p><p><strong>Limitations: </strong>Data-collection occurred during the COVID-19 pandemic.</p><p><strong>Conclusions: </strong>Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"23"},"PeriodicalIF":6.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237954","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":"Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms.","authors":"Eric Courchesne, Vani Taluja, Sanaz Nazari, Caitlin M Aamodt, Karen Pierce, Kuaikuai Duan, Sunny Stophaeros, Linda Lopez, Cynthia Carter Barnes, Jaden Troxel, Kathleen Campbell, Tianyun Wang, Kendra Hoekzema, Evan E Eichler, Joao V Nani, Wirla Pontes, Sandra Sanchez Sanchez, Michael V Lombardo, Janaina S de Souza, Mirian A F Hayashi, Alysson R Muotri","doi":"10.1186/s13229-024-00602-8","DOIUrl":"10.1186/s13229-024-00602-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with \"profound\" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations: &lt;/strong&gt;Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;By embryogenesis, t","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"22"},"PeriodicalIF":6.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093745","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":"Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium.","authors":"Hannah E Laue, Kevin S Bonham, Modupe O Coker, Yuka Moroishi, Wimal Pathmasiri, Susan McRitchie, Susan Sumner, Anne G Hoen, Margaret R Karagas, Vanja Klepac-Ceraj, Juliette C Madan","doi":"10.1186/s13229-024-00597-2","DOIUrl":"10.1186/s13229-024-00597-2","url":null,"abstract":"<p><strong>Background: </strong>Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors.</p><p><strong>Methods: </strong>Utilizing the Environmental influences on Children Health Outcomes (ECHO) consortium of United States (U.S.) pediatric cohorts, we gathered data on 304 participants with fecal metagenomic sequencing between 6-weeks to 2-years postpartum (481 samples). ASD-related social development was assessed with the Social Responsiveness Scale (SRS-2). Linear regression, PERMANOVA, and Microbiome Multivariable Association with Linear Models (MaAsLin2) were adjusted for sociodemographic factors. Stratified models estimated sex-specific effects.</p><p><strong>Results: </strong>Genes encoding pathways for synthesis of short-chain fatty acids were associated with higher SRS-2 scores, indicative of ASDs. Fecal concentrations of butyrate were also positively associated with ASD-related SRS-2 scores, some of which may be explained by formula use.</p><p><strong>Limitations: </strong>The distribution of age at outcome assessment differed in the cohorts included, potentially limiting comparability between cohorts. Stool sample collection methods also differed between cohorts. Our study population reflects the general U.S. population, and thus includes few participants who met the criteria for being at high risk of developing ASD.</p><p><strong>Conclusions: </strong>Our study is among the first multicenter studies in the U.S. to describe prospective microbiome development from infancy in relation to neurodevelopment associated with ASDs. Our work contributes to clarifying which microbial features associate with subsequent diagnosis of neuropsychiatric outcomes. This will allow for future interventional research targeting the microbiome to change neurodevelopmental trajectories.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"21"},"PeriodicalIF":6.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957630","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":"Moral foundations in autistic people and people with systemizing minds.","authors":"Yeshaya David M Greenberg, Rosemary Holt, Carrie Allison, Paula Smith, Robbie Newman, Theo Boardman-Pretty, Jonathan Haidt, Simon Baron-Cohen","doi":"10.1186/s13229-024-00591-8","DOIUrl":"10.1186/s13229-024-00591-8","url":null,"abstract":"<p><strong>Background: </strong>Do autistic people share the same moral foundations as typical people? Here we built on two prominent theories in psychology, moral foundations theory and the empathizing-systemizing (E-S) theory, to observe the nature of morality in autistic people and systemizers.</p><p><strong>Methods: </strong>In dataset 1, we measured five foundations of moral judgements (Care, Fairness, Loyalty, Authority, and Sanctity) measured by the Moral Foundations Questionnaire (MFQ) in autistic (n = 307) and typical people (n = 415) along with their scores on the Empathy Quotient (EQ) and Systemizing Quotient (SQ). In dataset 2, we measured these same five foundations along with E-S cognitive types (previously referred to as \"brain types\") in a large sample of typical people (N = 7595).</p><p><strong>Results: </strong>Autistic people scored the same on Care (i.e., concern for others) as typical people (h1). Their affective empathy (but not their cognitive empathy) scores were positively correlated with Care. Autistic people were more likely to endorse Fairness (i.e., giving people what they are owed, and treating them with justice) over Care (h2). Their systemizing scores were positively correlated with Fairness. Autistic people or those with a systemizing cognitive profile had lower scores on binding foundations: Loyalty, Authority, and Sanctity (h3). Systemizing in typical people was positively correlated with Liberty (i.e., hypervigilance against oppression), which is a sixth moral foundation (h4). Although the majority of people in all five E-S cognitive types self-identified as liberal, with a skew towards empathizing (h5), the percentage of libertarians was highest in systemizing cognitive types (h6). E-S cognitive types accounted for 2 to 3 times more variance for Care than did sex.</p><p><strong>Limitations: </strong>Our study is limited by its reliance on self-report measures and a focus on moral judgements rather than behavior or decision-making. Further, only dataset 2 measured political identification, therefore we were unable to assess politics in autistic people.</p><p><strong>Conclusions: </strong>We conclude that some moral foundations in autistic people are similar to those in typical people (despite the difficulties in social interaction that are part of autism), and some are subtly different. These subtle differences vary depending on empathizing and systemizing cognitive types.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"20"},"PeriodicalIF":6.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921217","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}