Autism Spectrum Disorder Risk Research Articles

Molecular basis of the CYFIP2 and NCKAP1 autism-linked variants in the WAVE regulatory complex.

The WAVE regulatory pentameric complex regulates actin remodeling. Two components of it (CYFIP2 and NCKAP1) are encoded by genes whose genetic mutations increase the risk for autism spectrum disorder (ASD) and related neurodevelopmental disorders. Here, we use a newly developed computational protocol and hotspot analysis to uncover the functional impact of these mutations at the interface of the correct isoforms of the two proteins into the complex. The mutations turn out to be located on the surfaces involving the largest number of hotspots of the complex. Most of them decrease the affinity of the proteins for the rest of the complex, but some have the opposite effect. The results are fully consistent with the available experimental data. The observed changes in the WAVE regulatory complex stability might impact on complex activation and ultimately play a role in the aberrant pathway of the complex, leading to the cell derangement associated with the disease.

The intersection of inflammation and DNA damage as a novel axis underlying the pathogenesis of autism spectrum disorders.

Autism spectrum disorders (ASD) affects 1 in 36 children and is characterized by repetitive behaviors and difficulties in social interactions and social communication. The etiology of ASD is extremely heterogeneous, with a large number of ASD cases that are of unknown or complex etiology, which suggests the potential contribution of epigenetic risk factors. In particular, epidemiological and animal model studies suggest that inflammation during pregnancy could lead to an increased risk of ASD in the offspring. However, the molecular mechanisms that contribute to ASD pathogenesis in relation to maternal inflammation during pregnancy in humans are underexplored. Several pro-inflammatory cytokines have been associated with increased autistic-like behaviors in animal models of maternal immune activation, including IL-17A. Using a combination of ASD patient lymphocytes and stem cell-derived human neurons exposed to IL-17A we discovered a shared molecular signature that highlights a metabolic and translational node that could lead to altered neuronal excitability. Further, our work on human neurons brings forward the possibility that defects in the DNA damage response could be underlying the effect of IL-17A on human excitatory neurons, linking exacerbated unrepaired DNA damage to the pathogenicity of maternal inflammation in connection to ASD.

Profiles of early expressive vocabulary in children with typical and atypical language development

The development of early childhood vocabulary is influenced by both biological and environmental factors, which shape language acquisition. This research investigates the variability in early expressive vocabulary among typically developing children (TD), Late Talkers (LTs), and those at risk for neurodevelopmental conditions like Autism Spectrum Disorder (ASD), and Developmental Language Disorder (DLD). Participants included 132 Mexican Spanish-speaking children: 37 with TD (M = 24.89, SD =4.01), 37 LTs (M = 24.78, SD 3.51), 41 at risk for ASD (M = 24.39, SD = 4.31) and 17 at risk for DLD (M = 37.71, SD = 4.50). The MacArthur-Bates Communicative Development Inventory II was utilized to assess 23 vocabulary categories, which were grouped into six broader categories (nouns, verbs, adjectives-adverbs, functional words, routines and sounds-onomatopoeias). The results indicated differences in vocabulary distribution among the groups. Although TD children generally exhibited the highest performance, there was notable variability within this group. Both LTs and children at risk for ASD showed differences compared to TD children, with LTs demonstrating the most reduced lexical usage. Children at risk for DLD and LTs displayed similar lexical profiles, characterized by reduced use of verbs and functional words. LTs and most children at risk for ASD exhibited low usage across all vocabulary categories. This analysis identified distinct vocabulary profiles among TD, LTs, ASD, and DLD groups, with variability across vocabulary categories reflecting the unique characteristics of each group. These findings enhance our understanding of the heterogeneity in early language development across clinical populations.

A Machine Learning Framework for Early-Stage Detection of Autism Spectrum Disorders

Autism Spectrum Disorder (ASD) is a neuro developmental condition that significantly impacts the daily lives of those affected. While complete eradication remains challenging, early interventions can help alleviate its severity. This study presents a novel framework for assessing various Machine Learning (ML) techniques to detect ASD early. The framework incorporates four Feature Scaling (FS) methods—Quantile Transformer (QT), Power Transformer (PT), Normalizer, and Max Abs Scaler (MAS). Subsequently, the scaled datasets are subjected to classification using eight ML algorithms: Ada Boost (AB), Random Forest (RF), Decision Tree (DT), K-Nearest Neighbors (KNN), Gaussian Naïve Bayes (GNB), Logistic Regression (LR), Support Vector Machine (SVM), and Linear Discriminant Analysis (LDA). Experiments are conducted on four established ASD datasets categorizing individuals by age groups—Toddlers, Adolescents, Children, and Adults. By evaluating classification outcomes through diverse statistical metrics such as Accuracy, Receiver Operating Characteristic (ROC) curve, F1-score, Precision, Recall, Mathews Correlation Coefficient (MCC), Kappa score, and Log loss, optimal classification methods and FS techniques are determined for each dataset. Results show AB achieving the highest accuracy of 99.25% for Toddlers and 97.95% for Children, while LDA achieves 97.12% for Adolescents and 99.03% for Adults. Notably, using normalizer FS for Toddlers and Children, and QT FS for Adolescents and Adults yield the best accuracies. Furthermore, ASD risk factors are quantified, and attribute importance is ranked employing four Feature Selection Techniques (FSTs)—Info Gain Attribute Evaluator (IGAE), Gain Ratio Attribute Evaluator (GRAE), Relief F Attribute Evaluator (RFAE), and Correlation Attribute Evaluator (CAE). These comprehensive evaluations underscore the significance of fine-tuning ML methodologies for accurate ASD prediction across different age groups. The detailed analysis of feature importance presented herein can aid healthcare practitioners in ASD screening, offering promising advancements compared to existing detection approaches.

Genotype-Phenotype Correlations in SYNGAP1-Related Mental Retardation Type 5.

Variants in the SYNGAP1 gene leading to decreased SynGAP protein expression are critical for the pathogenesis of mental retardation type 5 (MRD5). This study aims to explore the relationship between SYNGAP1 genotype and clinical phenotype through an expanded sample size, thereby enhancing the understanding of the specific mechanisms underlying MRD5. Data from previously published cases of patients with SYNGAP1 mutations were collected, and the relationship between genotype and clinical phenotype was analyzed. A total of 246 MRD5 patients were included in the analysis. Among them, 98.7% (224/227) were diagnosed with intellectual disability (ID), 91.6% (208/227) with epilepsy, and 57.3% (137/239) with autism spectrum disorder (ASD). The clinical phenotypes of MRD5 patients were found to be associated with their genotypes. Variants located in exons 1 to 6 may correlate with milder ID and reduced risk of ASD, yet they are more likely to present as refractory epilepsy.

Counteracting the effects of maternal obesity on offspring neurodevelopment through Omega-3-based nutritional strategies.

It is becoming increasingly recognized that, in addition to psychological stress, unbalanced maternal nutritional habits can thwart fetal brain development. Maternal obesity is one of the most pressing public health problems facing the world today, as about 40% of pregnant women are obese or gain excessive weight worldwide. This condition can negatively impact offspring's brain development, increasing the risk for autism spectrum disorders, cognitive deficits, attention deficit hyperactivity disorder, as well as anxiety and depression. In the context of fetal development, nutritional interventions may represent a feasible and safe approach for preventing the negative effects of maternal obesity. We argue that maternal Omega-3 supplementation, among the many dietary strategies available, is especially promising as it buffers oxidative stress and inflammation, both recognized as candidate mechanisms underlying the long-term effects of maternal obesity on the offspring. Notwithstanding the current knowledge, both preclinical studies and clinical trials are needed to refine current strategies addressing dietary content and length of administration according to individual characteristics and needs.

Effect of Genetics on Autism Spectrum Disorders: A Review Study

Autism Spectrum Disorders (ASD) are intricate neurodevelopmental conditions marked by challenges in social interaction, communication, and repetitive behaviors. The etiology of ASD is multifaceted, involving genetic mutations, perinatal, nutritional and environmental factors. This review explores the various genetic mutations implicated in the development of ASD for the purpose of examining the diverse genetic factors contributing to the pathogenesis of ASD such as SHANK3, SCGN, ADNP, ARID1B, CHD8, DYRK1A, KMT2C, OT, AVP and zinc transporter genes. A comprehensive review of literature was conducted to gather information on genetic influences related to ASD. Studies investigating the complex interplay of those factors were analyzed to elucidate how they contribute to the development of ASD. Results found that genetic mutations in genes like Shank3 and SCGN have been identified as playing a role in the pathogenesis of ASD through their impact on glutamic excitatory pathways and oxytocin signaling. ADNP, ARID1B, CHD8, DYRK1A, KMT2C, OT, AVP and zinc transporter genes have also been linked to an increased risk of ASD and associated cognitive and neurological impairments. In conclusion, research on different genetic mutations and deletions affecting autism spectrum disorder (ASD) highlights the complexity of the disease. Key genes such as SHANK3, SCGN, ADNP, ARID1B, CHD8, DYRK1A, and KMT2C are implicated, each contributing uniquely to ASD. Genetic variations, mutations, and heritability play significant roles, with factors like zinc deficiency and advanced paternal age also linked to increased ASD risk. While genomic technology has identified specific markers and pathways, the effect of multiple genetic mutations on symptom severity remains unclear. Understanding these genetic factors is crucial for improving diagnostic precision and developing targeted therapies, necessitating continued interdisciplinary research.

Review of structural neuroimaging and genetic findings in autism spectrum disorder- a clinical perspective.

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by deficits in social relationships and communication and restrictive, repetitive behaviors and interests. ASDs form a heterogeneous group from a clinical and genetic perspective. Currently, ASDs diagnosis is based on the clinical observation of the individual's behavior. The subjective nature of behavioral diagnoses, in the context of ASDs heterogeneity, contributes tosignificant variation in the age at ASD diagnosis. Early detection has been proved to be critical in ASDs, as early start of appropriate therapeutic interventions greatly improve the outcome for some children. Structural magnetic resonance imaging (MRI) is widely used in the diagnostic work-up of neurodevelopmental conditions, including ASDs, mostly for brain malformations detection. Recently, the focus of brain imaging shifted towards quantitative MRI parameters, aiming to identify subtle changes that may establish early detection biomarkers. ASDs have a strong genetic component; deletions and duplications of several genomic loci have been strongly associated with ASDs risk. Consequently, a multitude of neuroimaging and genetic findings emerged in ASDs in the recent years. The association of gross or subtle changes in brain morphometry and volumes with different genetic defects has the potential to bring new insights regarding normal development and pathomechanisms of various disorders affecting the brain. Still, the clinical implications of these discoveries and the impact of genetic abnormalities on brain structure and function are unclear. Here we review the literature on brain imaging correlated with the most prevalent genomic imbalances in ASD, and discuss the potential clinical impact.

CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning.

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations into how ASD-risk genes alter development. Most functional genomics studies have focused on the role of these genes in neurons and neural progenitor cells. However, roles for ASD risk genes in other cell types are largely uncharacterized. There is evidence from postmortem tissue that microglia, the resident immune cells of the brain, appear activated in ASD. Here, we used CRISPRi-based functional genomics to systematically assess the impact of ASD risk gene knockdown on microglia activation and phagocytosis. We developed an iPSC-derived microglia-neuron coculture system and high-throughput flow cytometry readout for synaptic pruning to enable parallel CRISPRi-based screening of phagocytosis of beads, synaptosomes, and synaptic pruning. Our screen identified ADNP, a high-confidence ASD risk genes, as a modifier of microglial synaptic pruning. We found that microglia with ADNP loss have altered endocytic trafficking, remodeled proteomes, and increased motility in coculture.

Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder

This study explores the association between genetic variations in the vitamin D pathway and autism spectrum disorder (ASD) susceptibility and severity in Thai children. A total of 276 participants, including 169 children with ASD and 107 healthy controls, were recruited. Genotyping of vitamin D pathway genes (CYP2R1, CYP27B1, GC, and VDR) was conducted using TaqMan-based real-time PCR, while serum vitamin D levels were measured by chemiluminescence immunoassay. ASD severity was assessed via the Childhood Autism Rating Scale, 2nd Edition. Results reveal that the VDR gene (ApaI) rs7975232 is linked to a reduced ASD risk. In contrast, the GC gene rs7041 (A > C) polymorphism shows a significant association with increased ASD risk and severity, particularly in individuals with both the GC gene polymorphism and vitamin D insufficiency. Additionally, there was a higher prevalence of the GC1s isoform and GC1s-GC1s haplotype in children with ASD, associated with ASD severity. This study identified that individuals possessing GC rs7041 C alleles and the GC1s genotype (rs7041C/rs4588G) exhibit an increased susceptibility to and more severity of ASD. Further studies with larger cohorts are essential to fully understand these genetic polymorphisms’ roles.

Mitochondrial related Mendelian randomization identifies causal associations between metabolic disorders and childhood neurodevelopmental disorders.

Childhood neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder, and Tourette syndrome, are a predominant cause of health-related disabilities in children and adolescents. Nevertheless, disease biomarkers are still limited. The aim of this study was to evaluate the potential, causal relationship between mitochondrial DNA copy number (mtDNA-CN), metabolic disorders, and childhood NDDs using the two-sample Mendelian randomization (MR) method. Genetic associations with mtDNA-CN, disorders of lipoprotein metabolism, and disorders of iron metabolism were selected as exposures, and genome-wide association data from ASD, attention-deficit hyperactivity disorder, and Tourette syndrome were utilized as outcomes. Results of the study suggested that a high degree of disordered lipoprotein metabolism related increases in ASD risk result from a decrease in mtDNA-CN (disordered lipoprotein metabolism-mtDNA: inverse variance weighting β: -0.03, 95% confidence interval: -0.05 to -0.02, P = 2.08 × 10-5; mtDNA-CN-ASD: inverse variance weighting odds ratio: 0.83, 95% confidence interval: 0.69-0.99, P = .034). The research findings implied that mtDNA-CN can mediate disorders of lipoprotein metabolism, potentially influencing the development of ASD. The potential impact of the results of this study for the prevention and treatment of childhood NDDs warrants validation in robust randomized clinical trials.

Development and evaluation of an autism pig model

Developing cost-effective and disease-relevant animal models is essential for advancing biomedical research into human disorders. Here we investigate the feasibility of a pig model for autism spectrum disorder (ASD) using embryonic exposure to valproic acid (VPA), an antiepileptic drug known to increase ASD risk. We established experimental paradigms to assess the behavioral characteristics of these pig models. Administration of VPA to Bama miniature pigs (Sus scrofa domestica) during critical embryonic stages resulted in abnormal gait, increased anxiety levels, reduced learning capabilities and altered social patterns, while largely preserving social preference of treated piglets. Notably, we detected significant neuroanatomical changes in cortical regions associated with ASD in the VPA-treated pigs, including cortical malformation, increased neuronal soma size, decreased dendritic complexity and reduced dendritic spine maturation. Transcriptome analysis of the prefrontal cortex of VPA-treated pigs further revealed substantial alterations in the expression of genes linked to ASD, especially genes of the dopamine signaling pathway, highlighting the model’s relevance and potential for shedding light on ASD’s underlying neuropathological and molecular mechanisms. These findings suggest that pig models could serve as a promising alternative to traditional rodent models and provide a more ethical substitute for the use of primates in translational research on neurodevelopmental disorders.

Air pollution: an emerging risk factor for autism spectrum disorder

The global surge in air pollution poses an increasingly concerning environmental risk factor for neurodevelopmental disorders, particularly autism spectrum disorder (ASD). Recent epidemiological studies have revealed compelling associations between exposure to specific air pollutants, including fine particulate matter (PM), nitrogen oxides (NO, NO2), sulfur dioxide (SO2) and ozone (O3), and increased ASD risk. While the rising global ASD prevalence, now affecting 1%–1.5% of the population, partially reflects expanded diagnostic criteria and enhanced screening, mounting evidence points to the critical role of gene–environment interactions in ASD etiology. Air pollutants can trigger multiple pathogenic mechanisms, including neuroinflammation, oxidative/nitrosative stress, epigenetic modifications, and glutamatergic/GABAergic neurotransmitter system disruption. The timing of exposure appears crucial, with heightened vulnerability during prenatal development and early childhood when critical neurodevelopmental processes, such as neuronal migration, synaptogenesis, and myelination occur. Research priorities should focus on how air pollutants affect brain development in genetically susceptible individuals, especially during pregnancy and early childhood. Better ways are needed to identify individuals at the highest risk and develop practical protective measures. Given the rising global pollution levels, this knowledge will help shape meaningful public health policies to protect future generations from environmental factors that may contribute to ASD.

GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2−/− Cerebral Organoids

BackgroundThe polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations. MethodsWe developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the CNTNAP2 ASD risk gene. ResultsCNTNAP2−/− cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding. Proteomic analysis revealed disruptions in glutamatergic/GABAergic (gamma-aminobutyric acidergic) synaptic pathways and neurodevelopment, and transcriptomic analysis revealed differentially expressed genes belonging to inhibitory neuron–related gene networks. Interestingly, there was a weak correlation between the 2 datasets, suggesting nuanced translational control mechanisms. Along these lines, we found upregulated Akt/mTOR (mechanistic target of rapamycin) signaling in CNTNAP2−/− organoids. Spatial transcriptomic analysis of CNTNAP2−/− ventricular-like zones demonstrated pervasive changes in gene expression, implicating upregulation of cell cycle regulation, synaptic, and glutamatergic/GABAergic pathways. We noted significant overlap of all day 30 organoid omics datasets differentially expressed genes from idiopathic ASD (macrocephaly) induced pluripotent stem cell–derived telencephalic organoids, where FOXG1 was upregulated. Moreover, we detected increased GAD1- and decreased TBR1--expressing cells, suggesting altered GABAergic/glutamatergic neuron development. ConclusionsThese findings potentially highlight a shared mechanism in the early cortical development of various forms of ASD, further elucidate the role of CNTNAP2 in ASD pathophysiology and cortical development, and pave the way for targeted therapies that use cerebral organoids as preclinical models.

Identifying the impact of ARHGAP and MAP gene families on autism spectrum disorders.

The rising incidence of Autism Spectrum Disorder (ASD) has become a major concern, affecting children's psychological well-being and placing a significant strain on healthcare systems. Despite its impact, the etiological mechanisms underpinning ASD remain elusive. This study leveraged dorsolateral prefrontal cortex gene data from 452 individuals of European descent, sourced from the CommonMindConsortium, and examined ASD-related gene expression data from the Gene Expression Omnibus (GEO) database (GSE18123), along with Genome-Wide Association Studies (GWAS) data from the Lundbeck Foundation Integrated Psychiatric Research and Psychiatric Genomics Consortium. Expression quantitative trait loci data were sourced from the GTExv8 database. We employed Transcriptome-Wide Association Studies (TWAS) and Weighted Gene Co-expression Network Analysis (WGCNA) to pinpoint genes within ASD-associated susceptibility gene families (ARHGAP, MAP). Four genes-ARHGAP27, MAPT, ARHGAP19, and MAP1B-were scrutinized, and their biological implications were elucidated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-Protein Interaction (PPI) analysis and conditional analysis within the TWAS framework helped identify pivotal genes (ARHGAP27, MAPT). A subsequent verification phase involving Mendelian Randomization (MR) evaluated the potential causal links between the identified genes and ASD. The findings revealed no causal association between ARHGAP19, MAP1B, and ASD. In contrast, significant causal relationships were established for ARHGAP27 and MAPT, suggesting that ARHGAP27 may elevate ASD risk as a susceptibility gene, whereas MAPT appears to reduce the risk as a protective gene.

The pleiotropic spectrum of proximal 16p11.2 CNVs.

Recurrent genomic rearrangements at 16p11.2 BP4-5 represent one of the most common causes of genomic disorders. Originally associated with increased risk for autism spectrum disorder, schizophrenia, and intellectual disability, as well as adiposity and head circumference, these CNVs have since been associated with a plethora of phenotypic alterations, albeit with high variability in expressivity and incomplete penetrance. Here, we comprehensively review the pleiotropy associated with 16p11.2 BP4-5 rearrangements to shine light on its full phenotypic spectrum. Illustrating this phenotypic heterogeneity, we expose many parallels between findings gathered from clinical versus population-based cohorts, which often point to the same physiological systems, and emphasize the role of the CNV beyond neuropsychiatric and anthropometric traits. Revealing the complex and variable clinical manifestations of this CNV is crucial for accurate diagnosis and personalized treatment strategies for carrier individuals. Furthermore, we discuss areas of research that will be key to identifying factors contributing to phenotypic heterogeneity and gaining mechanistic insights into the molecular pathways underlying observed associations, while demonstrating how diversity in affected individuals, cohorts, experimental models, and analytical approaches can catalyze discoveries.

Association Between Exposure to Antibiotics During Pregnancy or Early Infancy and Risk of Autism Spectrum Disorder, Intellectual Disorder, Language Disorder, and Epilepsy in Children: Population Based Cohort Study

Association Between Exposure to Antibiotics During Pregnancy or Early Infancy and Risk of Autism Spectrum Disorder, Intellectual Disorder, Language Disorder, and Epilepsy in Children: Population Based Cohort Study

Association between combined use of epidural analgesia and oxytocin administration during labor and offspring outcomes: a narrative review and proposal.

Studies have suggested that the administration of epidural analgesia (Epi) and oxytocin (OT) during labor affects offspring outcomes. However, the effects of their combined use remain unclear. This article aimed to review the outcomes of offspring exposed to Epi and OT, identify research gaps, and discuss future research directions. We searched the MEDLINE/PubMed, Web of Science, and Cochrane Library databases to identify studies describing offspring outcomes in the Epi, OT, Epi-OT, and control groups. We included one systematic review, six cohort studies, and one case-control study. The offspring outcomes at birth did not differ between the Epi-OT and Epi groups. In the first hour of life, the pre-feeding and sucking behaviors of the Epi-OT group showed an inverse correlation. At 2 days of age, the breastfeeding behavior and skin temperature patterns differed significantly between the Epi-OT and other groups. At 4 days of age, hyperbilirubinemia was more prevalent in the Epi-OT versus control group. Behavioral scores at 1 month differed little among the Epi-OT, Epi, and control groups. No eligible studies examined 1 month to 1 year of life. From 1 to >13 years of age, the risk of autism spectrum disorder was higher in the Epi and Epi-OT groups versus the control group. Most eligible studies were small and observational without randomization, and the results were inconsistent. Additional large cohort studies of various aspects of offspring development are required to assess the long-term effects of Epi-OT administration.

Transdiagnostic and Diagnosis-Specific Morphological Similarity Related Transcriptional Profile in Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable developmental psychiatric disorders and exhibit a high degree of comorbidity. Our objective is to enhance understanding of the transdiagnostic and diagnosis-specific structural alterations and related cellular and genetic pathophysiological mechanisms between ADHD and ASD. We used structural magnetic resonance imaging data of 247 subjects from the publicly available 1000 Functional Connectomes Project, including 91 individuals with ADHD, 49 individuals with ASD, and 107 age- and sex-matched controls. We performed morphological similarity networks (MSN) and gene transcriptional profile analysis on these image data to identify the anatomical changes and MSN-related genes. Enrichment analysis was further conducted on ADHD/ASD risk genes and MSN-related genes. Individuals with ADHD showed the diagnosis-specific MSN changes distributing in areas related to high-level cognitive functions, whereas ASD had MSN changes in areas related to language comprehension and spatial location. ADHD and ASD exhibited the transdiagnostic morphological increase in the right middle temporal gyrus. Gene transcriptional profile analysis showed enrichment of ADHD and ASD risk genes in more than 10 biological processes, primarily including function of synapse transmission and development. Genes in excitatory and inhibitory neurons also enriched in pathways with similar function. The transdiagnostic morphological dedifferentiation in the right middle temporal gyrus might indicate the shared motion impairments in ADHD and ASD. Evidence from the transcription of MSN-related genes further indicates a potential imbalance in excitatory and inhibitory neural pathways in ADHD and ASD. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure diversity in experimental samples through the selection of the cell lines. We worked to ensure diversity in experimental samples through the selection of the genomic datasets. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

The Deficiency of the ASD-Related Gene CHD8 Disrupts Behavioral Patterns and Inhibits Hippocampal Neurogenesis in Mice.

Chromodomain helicase DNA-binding 8 (CHD8) is a gene that poses a high risk for autism spectrum disorder (ASD) and neurological development delay. Nevertheless, the impact of CHD8 haploinsufficiency on both hippocampus neurogenesis and behavior remains uncertain. Here, we performed behavioral assessments on male and female CHD8 heterozygous mice. The study discovered that both male and female CHD8 heterozygous mice displayed an impairment in preference for social novelty. Concurrently, CHD8 heterozygous mice exhibited anxiety-like behavior. However, its cognitive capacity for learning and memory is within the expected range. Furthermore, we discovered a reduction in the number of both immature and mature new neurons in mice with CHD8 heterozygous, resulting in an impeded neurogenesis process in the hippocampus. Taken together, our findings indicate that CHD8 plays a crucial role in the regulation of hippocampal neurogenesis, and further suggest that ASD-like behaviors observed in CHD8 heterozygous mice may be associated with disruptions in hippocampal neurogenesis.