Autism research : official journal of the International Society for Autism Research最新文献

{"title":"Cortical Thickness Differences in Autistic Children With and Without Intellectual Disability.","authors":"Derek S Andrews, Andrew J Dakopolos, Joshua K Lee, Brianna Heath, Devani Cordero, Marjorie Solomon, David G Amaral, Christine Wu Nordahl","doi":"10.1002/aur.3313","DOIUrl":"https://doi.org/10.1002/aur.3313","url":null,"abstract":"<p><p>Of the 1 in 36 individuals in the United States who are diagnosed with autism spectrum disorder, nearly 40% also have intellectual disability (ID). The cortex has been widely implicated in neural processes underlying autistic behaviors as well as intellectual ability. Thus, neuroimaging features such as cortical thickness are of particular interest as a possible biomarkers of the condition. However, neuroimaging studies often fail to include autistic individuals with ID. As a result, there are few studies of cortical thickness in autistic individuals across the entire range of intellectual abilities. This study used MRI to evaluate cortical thickness in young autistic children (n = 88, mean age 5.37 years) with a large range of intellectual ability (IQ 19-133) as well as nonautistic, nondevelopmentally delayed (referred to here as typically developing [TD]) peers (n = 53, mean age 5.29 years). We first investigated associations between full scale IQ and cortical thickness in both autistic and TD children. Autistic children had significant negative associations (i.e., thinner cortex, higher IQ) in bilateral entorhinal cortex, right fusiform gyrus, superior, middle and inferior temporal gyri, and right temporal pole that were not present in TD children. Significantly thicker cortex was also observed in these regions for autistic children with ID (i.e., IQ ≤ 70) compared with those without. Last, given the reported correspondence between the severity of autism symptoms and intellectual ability, we compared cortical thickness associations with both IQ and ADOS Calibrated Severity Scores and found these patterns overlapped to a significant degree across the cortex.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naa15 Haploinsufficiency and De Novo Missense Variants Associate With Neurodevelopmental Disorders and Interfere With Neurogenesis and Neuron Development.","authors":"Mei He, Bing Du, Guodong Chen, Yongqing Lyu, Hui Guo, Xiangbin Jia, Kun Xia","doi":"10.1002/aur.3308","DOIUrl":"https://doi.org/10.1002/aur.3308","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDDs) encompass a group of conditions that impact brain development and function, exhibiting significant genetic and clinical heterogeneity. NAA15, the auxiliary subunit of the N-terminal acetyltransferase complex, has garnered attention due to its association with NDDs. However, the precise role of NAA15 in cortical development and its contribution to NDDs remain elusive. By employing targeted sequencing on a large Chinese cohort affected by ASD and conducting an extensive literature review, we have compiled 64 distinct variants in the NAA15 gene identified among individuals with neurodevelopmental disorders. Our research demonstrates that loss of NAA15 leads to a substantial increase in neuronal count, potentially resulting in aberrant brain development and triggering repetitive as well as anxious behaviors in mice models. Furthermore, disorder-associated variants within NAA15 impair axon and synapse formation processes crucial for neural connectivity establishment. These findings shed light on the consequences of NAA15 deficiency along with its de novo mutations on brain development while unraveling the cellular mechanisms underlying NDDs.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demographic Correlates of Autism: How Do Associations Compare Between Diagnosis and a Quantitative Trait Measure?","authors":"Kristen Lyall, Aisha S Dickerson, Annette M Green, Seth Frndak, Lisa A Croen, Jennifer L Ames, Lyndsay A Avalos, Judy L Aschner, Nicole R Bush, Carlos A Camargo, Viren D'Sa, Stephen R Dager, Anne L Dunlop, Assiamira Ferrara, Jody M Ganiban, James E Gern, Tre D Gissandaner, J Carolyn Graff, Irva Hertz-Picciotto, Alison E Hipwell, Tengfei Ma, Meghan Miller, Laura Murphy, Margaret R Karagas, Rachel S Kelly, Amy Margolis, Daphne Koinis-Mitchell, Cindy T McEvoy, Daniel Messinger, Ruby Nguyen, Emily Oken, Sally Ozonoff, Grier P Page, Susan L Schantz, Rebecca J Schmidt, Coral L Shuster, Julie B Schweitzer, Stephen J Sheinkopf, Joseph B Stanford, Cindy O Trevino, Scott T Weiss, Heather E Volk, Robert M Joseph","doi":"10.1002/aur.3296","DOIUrl":"10.1002/aur.3296","url":null,"abstract":"<p><p>Prevalence of autism diagnosis has historically differed by demographic factors. Using data from 8224 participants drawn from the Environmental influences on Child Health Outcomes (ECHO) Program, we examined relationships between demographic factors and parent-reported autism-related traits as captured by the Social Responsiveness Scale (SRS; T score > 65) and compared these to relations with parent-reported clinician diagnosis of ASD, in generalized linear mixed effects regression analyses. Results suggested lower odds of autism diagnosis, but not of SRS T > 65, for non-Hispanic Black children (adjusted odds ratio [OR] = 0.76, 95% CI 0.55, 1.06) relative to non-Hispanic White children. Higher maternal education was associated with reduced odds of both outcomes (OR = 0.73, 95% CI 0.51, 1.05 for ASD autism diagnosis and 0.4, 95% CI 0.29, 0.55 for SRS score). In addition, results suggested a lower likelihood of autism diagnosis but a higher likelihood of an SRS score > 65 in Black girls. Findings suggest lower diagnostic recognition of autism in non-Hispanic Black children, despite a similar degree of SRS-assessed autism-related traits falling in the clinically elevated range. Further work is needed to address this disparity.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of mitochondrial DNA replisome in autism spectrum disorder: Exploring the role of replisome genes.","authors":"Valentina Rojas, Carlos Carrasco-Gallardo, Lidia Tenorio, Margrethe A Olesen, Victor Tapia, Manuel Carrasco, Patricio Araos, Rodrigo A Quintanilla, Lina M Ruiz","doi":"10.1002/aur.3277","DOIUrl":"https://doi.org/10.1002/aur.3277","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition often associated with mitochondrial dysfunction, including increased mitochondrial DNA (mtDNA) copy number and impaired energy production. This study investigates the role of the mitochondrial replisome-specifically, the genes TFAM, TWNK, POLG, and TOP1MT-in mtDNA replication and its potential contribution to ASD pathophysiology. We analyzed samples from the oral mucosa of children with ASD and typically developing (TD) controls, assessing mtDNA copy number, gene expression, and protein levels. Our findings revealed a significant increase in mtDNA copy number in the oral mucosa of ASD children, along with partially deleted mtDNA molecules. However, there were no significant changes in the expression of TFAM, TWNK, POLG, or MT-TL1 genes between ASD and TD samples. Additionally, TFAM protein levels, including monomeric, dimeric, and trimeric forms, did not differ significantly. We also observed increased oxidative stress and inflammatory markers in the oral mucosa of ASD children, suggesting that mitochondrial alterations may be linked to inflammation and oxidative damage in ASD. To further investigate the functional impact of TFAM, we overexpressed it in human HEK293 cells and cortical neurons (CN1.4). TFAM overexpression led to increased mtDNA copy number, cell proliferation, and ATP production in HEK293 cells, but did not significantly alter mitochondrial gene expression, protein oxidation, or mtDNA integrity. In CN1.4 neurons, TFAM overexpression increased mitochondrial membrane potential and length, indicating potential changes in mitochondrial dynamics. Overall, our study suggests that while mtDNA alterations are present in ASD, they are not directly driven by changes in mitochondrial replisome gene expression. These findings highlight the complexity of mitochondrial dysfunction in ASD and suggest the need for further investigation into the underlying molecular mechanisms.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detailed phenotyping of Tbr1-2A-CreER knock-in mice demonstrates significant impacts on TBR1 protein levels and axon development.","authors":"Marissa Co, Grace K O'Brien, Kevin M Wright, Brian J O'Roak","doi":"10.1002/aur.3271","DOIUrl":"10.1002/aur.3271","url":null,"abstract":"<p><p>Cre recombinase knock-in mouse lines have served as invaluable genetic tools for understanding key developmental processes altered in autism. However, insertion of exogenous DNA into the genome can have unintended effects on local gene regulation or protein function that must be carefully considered. Here, we analyze a recently generated Tbr1-2A-CreER knock-in mouse line, where a 2A-CreER cassette was inserted in-frame before the stop codon of the transcription factor gene Tbr1. Heterozygous TBR1 mutations in humans and mice are known to cause autism or autism-like behavioral phenotypes accompanied by structural brain malformations, most frequently a reduction of the anterior commissure (AC). Thus, it is critical for modified versions of Tbr1 to exhibit true wild-type-like activity. We evaluated the Tbr1-2A-CreER allele for its potential impact on Tbr1 function and complementation to Tbr1 loss-of-function alleles. In mice with one copy of the Tbr1-2A-CreER allele, we identified reduction of TBR1 protein in early postnatal cortex along with thinning of the AC, suggesting hypersensitivity of this structure to TBR1 dosage. Comparing Tbr1-2A-CreER and Tbr1-null mice to Tbr1-null complementation crosses showed reductions of TBR1 dosage ranging from 20% to 100%. Using six combinatorial genotypes, we found that moderate to severe TBR1 reductions (≥44%) were associated with cortical layer 5 expansion, while only the complete absence of TBR1 was associated with reeler-like \"inverted\" cortical layering. In total, these results strongly support the conclusion that Tbr1-2A-CreER is a hypomorphic allele. We advise caution when interpreting experiments using this allele, considering the sensitivity of various corticogenic processes to TBR1 dosage and the association of heterozygous TBR1 mutations with complex neurodevelopmental disorders.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction and association between multiple vitamins and social adaptability and severity of autism: A large-scale retrospective study from China.","authors":"Qi Liu, Dongchuan Yu","doi":"10.1002/aur.3241","DOIUrl":"https://doi.org/10.1002/aur.3241","url":null,"abstract":"<p><p>Since children with autism spectrum disorder (ASD) often exhibit selective eating behaviors, it is generally believed that they may have abnormal nutrient structure, leading to aberrant concentrations of some serum vitamins. However, previous studies on serum vitamins in individuals with ASD are mixed. Additionally, the interaction and association between multiple serum vitamin and ASD-related symptoms remain unclear. This study utilized a cross-sectional survey with a large sample size (n = 1235) from China to clarify previous mixed findings, and examine the interaction and association between multiple serum vitamins (including folic acid [FA], vitamin A [VA], vitamin E [VE], vitamin B12 [VB12], and vitamin D [VD]) and social adaptability and symptom severity in children with ASD. Findings found that symptom severity was negatively associated with concentrations of serum VA, VE, VB12, and VD; while, social adaptability was significantly associated with the natural log-transformed concentrations of FA and VB12. Finding also revealed the interaction of VA and VE on the association between both vitamins and severity of ASD symptoms, as well as the interaction of VB12 and FA on the association between both vitamins and social adaptability. In particular, the combination of low concentration of VA and high concentration of VE is associated with the lowest risk of being \"severely autistic\"; while, the combination of low concentration of FA and high concentration of VB12 is associated with the lowest risk of being \"poor social adaptability\". This study offers the evidence for the requirement of considering multiple vitamins comprehensively, as well as valuable references for revealing the association between vitamin disparities and food selectivity in children with ASD.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual and auditory attention in individuals with DYRK1A and SCN2A disruptive variants.","authors":"Caitlin M Hudac, Kelsey Dommer, Monique Mahony, Trent D DesChamps, Brianna Cairney, Rachel Earl, Evangeline C Kurtz-Nelson, Jessica Bradshaw, Raphael A Bernier, Evan E Eichler, Emily Neuhaus, Sara Jane Webb, Frederick Shic","doi":"10.1002/aur.3202","DOIUrl":"10.1002/aur.3202","url":null,"abstract":"<p><p>This preliminary study sought to assess biomarkers of attention using electroencephalography (EEG) and eye tracking in two ultra-rare monogenic populations associated with autism spectrum disorder (ASD). Relative to idiopathic ASD (n = 12) and neurotypical comparison (n = 49) groups, divergent attention profiles were observed for the monogenic groups, such that individuals with DYRK1A (n = 9) exhibited diminished auditory attention condition differences during an oddball EEG paradigm whereas individuals with SCN2A (n = 5) exhibited diminished visual attention condition differences noted by eye gaze tracking when viewing social interactions. Findings provide initial support for alignment of auditory and visual attention markers in idiopathic ASD and neurotypical development but not monogenic groups. These results support ongoing efforts to develop translational ASD biomarkers within the attention domain.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder.","authors":"Vardan Arutiunian, Megha Santhosh, Emily Neuhaus, Catherine A W Sullivan, Raphael A Bernier, Susan Y Bookheimer, Mirella Dapretto, Daniel H Geschwind, Allison Jack, James C McPartland, John D Van Horn, Kevin A Pelphrey, Abha R Gupta, Sara Jane Webb","doi":"10.1002/aur.3193","DOIUrl":"10.1002/aur.3193","url":null,"abstract":"<p><p>One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental-4 (CELF-4) and Vineland-II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF-4 measures but not Vineland-II in youth with ASD, follow-up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non-verbal individuals with ASD.</p>","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1111/mpp.13295","DOIUrl":"https://doi.org/10.1111/mpp.13295","url":null,"abstract":"","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42341964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1111/phpr.12792","DOIUrl":"https://doi.org/10.1111/phpr.12792","url":null,"abstract":"","PeriodicalId":72339,"journal":{"name":"Autism research : official journal of the International Society for Autism Research","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44225024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}