Molecular Autism最新文献

{"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}

{"title":"The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives.","authors":"Vardan Arutiunian, Megha Santhosh, Emily Neuhaus, Heather Borland, Chris Tompkins, Raphael A Bernier, Susan Y Bookheimer, Mirella Dapretto, Abha R Gupta, Allison Jack, Shafali Jeste, James C McPartland, Adam Naples, John D Van Horn, Kevin A Pelphrey, Sara Jane Webb","doi":"10.1186/s13229-024-00598-1","DOIUrl":"10.1186/s13229-024-00598-1","url":null,"abstract":"<p><strong>Background: </strong>Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance.</p><p><strong>Methods: </strong>We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals.</p><p><strong>Results: </strong>First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills.</p><p><strong>Limitations: </strong>We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis.</p><p><strong>Conclusions: </strong>Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"19"},"PeriodicalIF":6.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851507","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":"Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth","authors":"Blythe A. Corbett, Rachael A. Muscatello, Trey McGonigle, Simon Vandekar, Christina Burroughs, Sloane Sparks","doi":"10.1186/s13229-024-00600-w","DOIUrl":"https://doi.org/10.1186/s13229-024-00600-w","url":null,"abstract":"Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles.","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"19 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}