Molecular Autism最新文献

{"title":"Evolutionary constrained genes associated with autism spectrum disorder across 2,054 nonhuman primate genomes.","authors":"Yukiko Kikuchi, Mohammed Uddin, Joris A Veltman, Sara Wells, Christopher Morris, Marc Woodbury-Smith","doi":"10.1186/s13229-024-00633-1","DOIUrl":"10.1186/s13229-024-00633-1","url":null,"abstract":"<p><strong>Background: </strong>Significant progress has been made in elucidating the genetic underpinnings of Autism Spectrum Disorder (ASD). However, there are still significant gaps in our understanding of the link between genomics, neurobiology and clinical phenotype in scientific discovery. New models are therefore needed to address these gaps. Rhesus macaques (Macaca mulatta) have been extensively used for preclinical neurobiological research because of remarkable similarities to humans across biology and behaviour that cannot be captured by other experimental animals.</p><p><strong>Methods: </strong>We used the macaque Genotype and Phenotype (mGAP) resource consisting of 2,054 macaque genomes to examine patterns of evolutionary constraint in known human neurodevelopmental genes. Residual variation intolerance scores (RVIS) were calculated for all annotated autosomal genes (N = 18,168) and Gene Set Enrichment Analysis (GSEA) was used to examine patterns of constraint across ASD genes and related neurodevelopmental genes.</p><p><strong>Results: </strong>We demonstrated that patterns of constraint across autosomal genes are correlated in humans and macaques, and that ASD-associated genes exhibit significant constraint in macaques (p = 9.4 × 10^- 27). Among macaques, many key ASD-implicated genes were observed to harbour predicted damaging mutations. A small number of key ASD-implicated genes that are highly intolerant to mutation in humans, however, showed no evidence of similar intolerance in macaques (CACNA1D, MBD5, AUTS2 and NRXN1). Constraint was also observed across genes associated with intellectual disability (p = 1.1 × 10^- 46), epilepsy (p = 2.1 × 10^- 33) and schizophrenia (p = 4.2 × 10^- 45), and for an overlapping neurodevelopmental gene set (p = 4.0 × 10^- 10).</p><p><strong>Limitations: </strong>The lack of behavioural phenotypes among the macaques whose genotypes were studied means that we are unable to further investigate whether genetic variants have similar phenotypic consequences among nonhuman primates.</p><p><strong>Conclusion: </strong>The presence of pathological mutations in ASD genes among macaques, along with evidence of similar genetic constraints to those in humans, provides a strong rationale for further investigation of genotype-phenotype relationships in macaques. This highlights the importance of developing primate models of ASD to elucidate the neurobiological underpinnings and advance approaches for precision medicine and therapeutic interventions.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"5"},"PeriodicalIF":6.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autistic and transgender/gender diverse people's experiences of health and healthcare.","authors":"Kate Green, Elizabeth Weir, Lily Wright, Carrie Allison, Simon Baron-Cohen","doi":"10.1186/s13229-024-00634-0","DOIUrl":"10.1186/s13229-024-00634-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Autistic people and transgender/gender diverse people experience poorer healthcare experiences and greater risk of diagnosed, suspected, and assessment recommended health conditions, compared to non-autistic and cisgender individuals, respectively. Despite this, there is a paucity of studies on the healthcare experiences and health outcomes of transgender/gender diverse autistic individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We compared the healthcare experiences and health outcomes of cisgender autistic (n = 1094), transgender/gender diverse autistic (n = 174), and cisgender non-autistic adults (n = 1295) via an anonymous, self-report survey. All individuals whose sex assigned at birth did not match their current gender identity were categorized as transgender/gender diverse; this was possible to determine, as the survey asked about sex assigned at birth and gender in separate questions. Unfortunately, n = 57 transgender/gender diverse non-autistic participants were excluded from these analyses a priori, due to low power. Unadjusted and adjusted binomial logistic regression models with FDR correction were employed to assess healthcare experiences and rates of co-occurring mental and physical health conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Both transgender/gender diverse and cisgender autistic adults had higher rates of all health conditions (including conditions that are formally diagnosed, suspected, or recommended for assessment), compared to cisgender non-autistic adults. Transgender/gender diverse autistic adults were 2.3 times more likely to report a physical health condition, 10.9 times more likely to report a mental health condition, and 5.8 times more likely to report self-harm than cisgender non-autistic adults. Both autistic groups also reported significantly poorer healthcare experiences across 50/51 items.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations: &lt;/strong&gt;These data were not originally collected to understand the experiences of transgender/gender diverse individuals. In addition, our recruitment strategies, use of a convenience sampling method, and the use of a self-report survey limit the generalizability of the study. As our sample was biased towards white individuals, UK residents, relatively highly educated individuals, those assigned female at birth, and those who currently identify as female, our findings may be less applicable to individuals of differing demographics. Finally, the present study does not include information on the experiences of transgender/gender diverse non-autistic people.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Autistic people have poorer self-reported health and healthcare; however, being gender diverse is associated with further risk for certain adverse experiences and outcomes. Future research on the health and healthcare experiences of transgender/gender diverse autistic people is urgently needed. In particular, forthcoming studies in this area should aim to recruit large-scale and repres","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"4"},"PeriodicalIF":6.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008531","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 preference for surprise in reinforcement learning underlies the differences in developmental changes in risk preference between autistic and neurotypical youth.","authors":"Motofumi Sumiya, Kentaro Katahira, Hironori Akechi, Atsushi Senju","doi":"10.1186/s13229-025-00637-5","DOIUrl":"https://doi.org/10.1186/s13229-025-00637-5","url":null,"abstract":"<p><strong>Background: </strong>Risk preference changes nonlinearly across development. Although extensive developmental research on the neurotypical (NTP) population has shown that risk preference is highest during adolescence, developmental changes in risk preference in autistic (AUT) people, who tend to prefer predictable behaviors, have not been investigated. Here, we aimed to investigate these changes and underlying computational mechanisms.</p><p><strong>Method: </strong>We ran a game-like risk-sensitive reinforcement learning task on 75 participants aged 6-30 years (AUT group, n = 31; NTP group, n = 44). Focusing on choices between alternatives with the same objective value but different risks, we calculated the risk preference and stay probability of a risky choice after a rewarding or non-rewarding outcome. Analyses using t-tests and multiple regression analyses were conducted. Using the choice-related data of each participant, we fit four reinforcement learning models and compared the fit of each model to the data. Furthermore, we validated the results of model fitting with multiple methods, model recovery, parameter recovery, and posterior predictive check.</p><p><strong>Results: </strong>We found a significant difference in nonlinear developmental changes in risk preference between the AUT and NTP groups. The computational modeling approach with reinforcement learning models revealed that individual preferences for surprise modulated such preferences.</p><p><strong>Conclusions: </strong>These findings indicate that for NTP people, adolescence is a developmental period involving risk preference, possibly due to lower surprise aversion. Conversely, for AUT people, who show opposite developmental change of risk preference, adolescence could be a developmental period involving risk avoidance because of low surprise preference.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"3"},"PeriodicalIF":6.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008538","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":"Suboptimal but intact integration of Bayesian components during perceptual decision-making in autism.","authors":"Laurina Fazioli, Bat-Sheva Hadad, Rachel N Denison, Amit Yashar","doi":"10.1186/s13229-025-00639-3","DOIUrl":"10.1186/s13229-025-00639-3","url":null,"abstract":"<p><strong>Background: </strong>Alterations in sensory perception, a core phenotype of autism, are attributed to imbalanced integration of sensory information and prior knowledge during perceptual statistical (Bayesian) inference. This hypothesis has gained momentum in recent years, partly because it can be implemented both at the computational level, as in Bayesian perception, and at the level of canonical neural microcircuitry, as in predictive coding. However, empirical investigations have yielded conflicting results with evidence remaining limited. Critically, previous studies did not assess the independent contributions of priors and sensory uncertainty to the inference.</p><p><strong>Method: </strong>We addressed this gap by quantitatively assessing both the independent and interdependent contributions of priors and sensory uncertainty to perceptual decision-making in autistic and non-autistic individuals (N = 126) during an orientation categorization task.</p><p><strong>Results: </strong>Contrary to common views, autistic individuals integrated the two Bayesian components into their decision behavior, and did so indistinguishably from non-autistic individuals. Both groups adjusted their decision criteria in a suboptimal manner.</p><p><strong>Limitations: </strong>This study focuses on explicit priors in a perceptual categorization task and high-functioning adults. Thus, although the findings provide strong evidence against a general and basic alteration in prior integration in autism, they cannot rule out more specific cases of reduced prior effect - such as due to implicit prior learning, particular level of decision making (e.g., social), and level of functioning of the autistic person.</p><p><strong>Conclusions: </strong>These results reveal intact inference for autistic individuals during perceptual decision-making, challenging the notion that Bayesian computations are fundamentally altered in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"2"},"PeriodicalIF":6.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979420","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":"Molecular architecture of the altered cortical complexity in autism.","authors":"Makliya Mamat, Yiyong Chen, Wenwen Shen, Lin Li","doi":"10.1186/s13229-024-00632-2","DOIUrl":"10.1186/s13229-024-00632-2","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication challenges, and repetitive behaviors. Despite extensive research, the molecular mechanisms underlying these neurodevelopmental abnormalities remain elusive. We integrated microscale brain gene expression data with macroscale MRI data from 1829 participants, including individuals with ASD and typically developing controls, from the autism brain imaging data exchange I and II. Using fractal dimension as an index for quantifying cortical complexity, we identified significant regional alterations in ASD, within the left temporoparietal, left peripheral visual, right central visual, left somatomotor (including the insula), and left ventral attention networks. Partial least squares regression analysis revealed gene sets associated with these cortical complexity changes, enriched for biological functions related to synaptic transmission, synaptic plasticity, mitochondrial dysfunction, and chromatin organization. Cell-specific analyses, protein-protein interaction network analysis and gene temporal expression profiling further elucidated the dynamic molecular landscape associated with these alterations. These findings indicate that ASD-related alterations in cortical complexity are closely linked to specific genetic pathways. The combined analysis of neuroimaging and transcriptomic data enhances our understanding of how genetic factors contribute to brain structural changes in ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"1"},"PeriodicalIF":6.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951728","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":"Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome.","authors":"Siddhi S Ozarkar, Ridthi K-R Patel, Tasmai Vulli, Audrey L Smith, Martin A Styner, Li-Ming Hsu, Sung-Ho Lee, Yen-Yu Ian Shih, Heather C Hazlett, Mark D Shen, Alain C Burette, Benjamin D Philpot","doi":"10.1186/s13229-024-00636-y","DOIUrl":"10.1186/s13229-024-00636-y","url":null,"abstract":"<p><strong>Background: </strong>Angelman syndrome (AS), a severe neurodevelopmental disorder resulting from the loss of the maternal UBE3A gene, is marked by changes in the brain's white matter (WM). The extent of WM abnormalities seems to correlate with the severity of clinical symptoms, but these deficits are still poorly characterized or understood. This study provides the first large-scale measurement of WM volume reduction in children with AS. Furthermore, we probed the possibility of underlying WM neuropathology by examining the progression of myelination in an AS mouse model.</p><p><strong>Methods: </strong>We conducted magnetic resonance imaging (MRI) on children with AS (n = 32) and neurotypical controls (n = 99) aged 0.5-12 years. In parallel, we examined myelination in postnatal Ube3a maternal-null mice (Ube3a^m-/p+; AS model), Ube3a paternal-null mice (Ube3a^m+/p-), and wildtype controls (Ube3a^m+/p+) using MRI, immunohistochemistry, western blotting, and electron microscopy.</p><p><strong>Results: </strong>Our data revealed that AS individuals exhibit significant reductions in brain volume by ~ 1 year of age, and by 6-12 years of age WM is reduced by 26% and gray matter by 21%-approximately twice the reductions observed in the adult AS mouse model. Our AS mouse model saw a global delay in the onset of myelination, which normalized within days (likely corresponding to months or years in human development). This myelination delay is caused by the loss of UBE3A in neurons rather than UBE3A haploinsufficiency in oligodendrocytes. Interestingly, ultrastructural analyses did not reveal abnormalities in myelinated or unmyelinated axons.</p><p><strong>Limitations: </strong>It is difficult to extrapolate the timing and duration of the myelination delay observed in AS model mice to individuals with AS.</p><p><strong>Conclusions: </strong>This study reveals WM deficits as a hallmark in children with AS, demonstrating for the first time that these deficits are already apparent at 1 year of age. Parallel studies in a mouse model of AS show these deficits occur alongside the delayed onset of myelination, which results from the loss of neuronal (but not glial) UBE3A, though the causal relationship between these phenotypes remains to be determined. These findings emphasize the potential of WM as both a therapeutic target for interventions and a valuable biomarker for tracking the progression of AS and the effectiveness of potential treatments.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"54"},"PeriodicalIF":6.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896168","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":"Impact of chronic intranasal oxytocin administration on face expression processing in autistic children: a randomized controlled trial using fMRI.","authors":"Matthijs Moerkerke, Nicky Daniels, Stephanie Van der Donck, Tiffany Tang, Jellina Prinsen, Elahe' Yargholi, Jean Steyaert, Kaat Alaerts, Bart Boets","doi":"10.1186/s13229-024-00635-z","DOIUrl":"10.1186/s13229-024-00635-z","url":null,"abstract":"<p><strong>Background: </strong>Difficulties with (non-verbal) social communication, including facial expression processing, constitute a hallmark of autism. Intranasal administration of oxytocin has been considered a potential therapeutic option for improving social difficulties in autism, either by enhancing the salience of social cues or by reducing the social stress and anxiety experienced in social encounters.</p><p><strong>Methods: </strong>We recorded fMRI brain activity while presenting neutral, fearful and scrambled faces, to compare the neural face processing signature of autistic children (n = 58) with that of matched non-autistic controls (n = 38). Next, in the autistic children group, we implemented this fMRI face processing task in a double-blind, placebo-controlled, multiple-dose oxytocin clinical trial, to evaluate the impact of four-week repeated oxytocin administration (24 IU daily dose) on brain activity in face processing regions.</p><p><strong>Results: </strong>No significant diagnostic-group differences were identified between autistic versus non-autistic children with regard to neural face processing. Furthermore, no significant treatment effects were found in the oxytocin clinical trial. However, exploratory analyses (uncorrected for multiple comparisons) demonstrated decreases in brain activity in the left superior temporal sulcus (STS) and inferior frontal region in the oxytocin compared to the placebo group, and change-from-baseline analyses in the oxytocin group revealed significantly reduced neural activity in the core face-processing network (STS, inferior occipital, and posterior fusiform), as well as in amygdala and inferior frontal region.</p><p><strong>Conclusion: </strong>These findings suggest an attenuating effect of multiple-dose oxytocin administration on neural face processing, potentially supporting the anxiolytic account of oxytocin.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"53"},"PeriodicalIF":6.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872623","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":"Behavioral decline in Shank3^Δex4-22 mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes.","authors":"Rajaram Kshetri, James O Beavers, Romana Hyde, Roseline Ewa, Amber Schwertman, Sarahi Porcayo, Ben D Richardson","doi":"10.1186/s13229-024-00628-y","DOIUrl":"10.1186/s13229-024-00628-y","url":null,"abstract":"<p><strong>Background: </strong>SHANK3, a gene encoding a synaptic scaffolding protein, is implicated in autism spectrum disorder (ASD) and is disrupted in Phelan-McDermid syndrome (PMS). Despite evidence of regression or worsening of ASD-like symptoms in individuals with PMS, the underlying mechanisms remain unclear. Although Shank3 is highly expressed in the cerebellar cortical granule cells, its role in cerebellar function and contribution to behavioral deficits in ASD models are unknown. This study investigates behavioral changes and cerebellar synaptic alterations in Shank3^Δex4-22 mice at two developmental stages.</p><p><strong>Methods: </strong>Shank3^Δex4-22 wildtype, heterozygous, and homozygous knockout mice lacking exons 4-22 (all functional isoforms) were subjected to a behavioral battery in both juvenile (5-7 weeks old) and adult (3-5 months old) mouse cohorts of both sexes. Immunostaining was used to show the expression of Shank3 in the cerebellar cortex. Spontaneous excitatory postsynaptic currents (sEPSCs) from cerebellar granule cells (CGCs) were recorded by whole-cell patch-clamp electrophysiology.</p><p><strong>Results: </strong>Deletion of Shank3 caused deficits in motor function, heightened anxiety, and repetitive behaviors. These genotype-dependent behavioral alterations were more prominent in adult mice than in juveniles. Reduced social preference was only identified in adult Shank3^Δex4-22 knockout male mice, while self-grooming was uniquely elevated in males across both age groups. Heterozygous mice showed little to no changes in behavioral phenotypes in most behavioral tests. Immunofluorescence staining indicated the presence of Shank3 predominantly in the dendrite-containing rosette-like structures in CGCs, colocalizing with presynaptic markers of glutamatergic mossy fiber. Electrophysiological findings identified a parallel relationship between the age-related exacerbation of behavioral impairments and the enhancement of sEPSC amplitude in CGCs.</p><p><strong>Limitations: </strong>Other behavioral tests of muscle strength (grip strength test), memory (Barnes/water maze), and communication (ultrasonic vocalization), were not performed. Further study is necessary to elucidate how Shank3 modulates synaptic function at the mossy fiber-granule cell synapse in the cerebellum and whether these changes shape the behavioral phenotype.</p><p><strong>Conclusions: </strong>Our findings reveal an age-related exacerbation of behavioral impairments in Shank3^Δex4-22 mutant mice. These results suggest that Shank3 may alter the function of glutamatergic receptors at the mossy fiber-cerebellar granule cell synapse as a potential mechanism causing cerebellar disruption in ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"52"},"PeriodicalIF":6.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780507","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":"Harmonizing two measures of adaptive functioning using computational approaches: prediction of vineland adaptive behavior scales II (VABS-II) from the adaptive behavior assessment system II (ABAS-II) scores.","authors":"Corinna Smith, Alexandra Lautarescu, Tony Charman, Jennifer Crosbie, Russell J Schachar, Alana Iaboni, Stelios Georgiades, Robert Nicolson, Elizabeth Kelley, Muhammad Ayub, Jessica Jones, Paul D Arnold, Jason P Lerch, Evdokia Anagnostou, Azadeh Kushki","doi":"10.1186/s13229-024-00630-4","DOIUrl":"10.1186/s13229-024-00630-4","url":null,"abstract":"<p><strong>Background: </strong>Very large sample sizes are often needed to capture heterogeneity in autism, necessitating data sharing across multiple studies with diverse assessment instruments. In these cases, data harmonization can be a critical tool for deriving a single dataset for analysis. This can be done through computational approaches that enable the conversion of scores across various instruments. To this end, our study examined the use of analytical approaches for mapping scores on two measures of adaptive functioning, namely predicting the scores on the vineland adaptive behavior scales II (VABS) from the scores on the adaptive behavior assessment system II (ABAS).</p><p><strong>Methods: </strong>Data from the province of Ontario neurodevelopmental disorders network were used. The dataset included scores VABS and the ABAS for 720 participants (autism n = 547, 433 male, age: 11.31 ± 3.63 years; neurotypical n = 173, 95 male, age: 12.53 ± 4.05 years). Six regression approaches (ordinary least squares (OLS) linear regression, ridge regression, ElasticNet, LASSO, AdaBoost, random forest) were used to predict VABS total scores from the ABAS scores, demographic variables (age, sex), and phenotypic measures (diagnosis; core and co-occurring features; IQ; internalizing and externalizing symptoms).</p><p><strong>Results: </strong>The VABS scores were significantly higher than the ABAS scores in the autism group, but not the neurotypical group (median difference: 8, 95% CI = (7,9)). The difference was negatively associated with age (beta = -1.2 ± 0.12, t = -10.6, p < 0.0001). All estimators demonstrated similar performance, with no statistically significant differences in mean absolute error (MAE) values across estimators (MAE range: 4.96-6.91). The highest contributing features to the prediction model were ABAS composite score, diagnosis, and age.</p><p><strong>Limitations: </strong>This study has several strengths, including the large sample. We did not examine the conversion of domain scores across the two measures of adaptive functioning and suggest this as a future area of investigation.</p><p><strong>Conclusion: </strong>Overall, our results supported the feasibility of harmonization. Our results suggest that a linear regression model trained on the ABAS composite score, the ABAS raw domain scores, and age, sex, and diagnosis would provide an acceptable trade-off between accuracy, parsimony, and data collection and processing complexity.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"51"},"PeriodicalIF":6.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770453","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":"Socio-affective communication in Tph2-deficient rat pups: communal nesting aggravates growth retardation despite ameliorating maternal affiliation deficits.","authors":"Tianhua Wang, Judith R Homberg, Laura Boreggio, Marta C F Samina, Rogério C R Castro, Sharon M Kolk, Natalia Alenina, Michael Bader, Jinye Dai, Markus Wöhr","doi":"10.1186/s13229-024-00629-x","DOIUrl":"10.1186/s13229-024-00629-x","url":null,"abstract":"<p><strong>Background: </strong>A lack of serotonin (also known as 5-hydroxytryptamine, 5-HT) in the brain due to deficiency of the rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 2 (TPH2), was recently reported to result in impaired maternal affiliation across species, including mice, rats, and monkeys. In rodents, this was reflected in a lack of preference for maternal odors and reduced levels of isolation-induced ultrasonic vocalizations (USV), possibly contributing to a severe growth retardation phenotype.</p><p><strong>Methods: </strong>Here, we tested whether growth retardation, maternal affiliation deficits, and/or impairments in socio-affective communication caused by Tph2 deficiency can be rescued through early social enrichment in rats. To this aim, we compared male and female Tph2^-/- knockout and Tph2^+/- heterozygous rat pups to Tph2^+/+ wildtype littermate controls, with litters being randomly assigned to standard nesting (SN; one mother with her litter) or communal nesting (CN; two mothers with their two litters).</p><p><strong>Results: </strong>Our results show that Tph2 deficiency causes severe growth retardation, together with moderate impairments in somatosensory reflexes and thermoregulatory capabilities, partially aggravated by CN. Tph2 deficiency further led to deficits in socio-affective communication, as evidenced by reduced emission of isolation-induced USV, associated with changes in acoustic features, clustering of subtypes, and temporal organization. Although CN did not rescue the impairments in socio-affective communication, CN ameliorated the maternal affiliation deficit caused by Tph2 deficiency in the homing test. To close the communicative loop between mother and pup, we assessed maternal preference and showed that mothers display a preference for Tph2^+/+ controls over Tph2^-/- pups, particularly under CN conditions. This is consistent with the aggravated growth phenotype in Tph2^-/- pups exposed to the more competitive CN environment.</p><p><strong>Conclusion: </strong>Together, this indicates that CN aggravates growth retardation despite ameliorating maternal affiliation deficits in Tph2-deficient rat pups, possibly due to reduced and acoustically altered isolation-induced USV, hindering efficient socio-affective communication between mother and pup.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"15 1","pages":"50"},"PeriodicalIF":6.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755401","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}