Autism Spectrum Disorder Risk Research Articles

Decomposing the variance: The unique and shared associations of fine and ultrafine particulate matter exposed during pregnancy with child autism spectrum disorder

While fine particulate matter (PM2.5) has been associated with autism spectrum disorder (ASD), few studies focused on ultrafine particles (PM0.1). Given that fine and ultrafine particles can be highly correlated due to shared emission sources, challenges remain to distinguish their health effects. In a retrospective cohort of 318,371 mother-child pairs (4549 ASD cases before age 5) in Southern California, pregnancy average PM2.5 and PM0.1 were estimated using a California-based chemical transport model and assigned to residential addresses. The correlation between PM2.5 and PM0.1 was 0.87. We applied a two-step variance decomposition approach: first, decomposing PM2.5 and PM0.1 into the shared and unique variances using ordinary least squares linear regression (OLS) and Deming regression considering errors in both exposures; then assessing associations between decomposed PM2.5 and PM0.1 and ASD using Cox proportional hazard models adjusted for covariates. Prenatal PM2.5 and PM0.1 each was associated with increased ASD risk. OLS decomposition showed that associations were driven mainly by their shared variance, not by their unique variance. Results from Deming regression considering assumptions of measurement errors were consistent with those from OLS. This decomposition approach has potential to disentangle health effects of correlated exposures, such as PM2.5 and PM0.1 from common emissions sources.

Autistic-like social communication disorders and sensory profile in visually impaired children: Similarity and divergence with autism spectrum disorders

This study examined the sensory profile of three groups of children (those with visual impairment, typical development or autism spectrum disorder) aged 3 to 12. The principal aim was to find out whether the Sensory Profile (SP) of children with visual impairment was a good predictor of behaviors typical of ASD. The data was collected through a sensory profile filled out by parents of 37 visually impaired children, 30 with autism spectrum disorder (ASD) and 42 with typical development (TD). To assess the risk of ASD, the Social Communication Questionnaire (SCQ) was also administered. The results indicate that children with visual impairment are at increased risk of exhibiting signs of ASD, and that the sensory profile is a good predictor of risk of autistic signs in children with visual impairment. This study provides for the first time strong evidence for the need to systematically assess the sensory profile in children with visual impairment.

Predicting autism from young Infants' empathic responding: A prospective study.

Difficulties in empathy are frequent among children with autism spectrum disorder (ASD), and often considered a core feature of autism. Reduced empathy during the second year of life has been shown to predict subsequent ASD diagnosis. However, links between empathy in the first year and ASD have not yet been investigated. Moreover, prior work focused on empathy for others' distress but not for others' joy. To address these gaps, this prospective longitudinal study followed 60 infants (33% girls), 39 at high genetic risk of ASD (siblings of children with ASD) and a matching control group. Infants' empathic responses to others' distress and happiness were assessed at ages 6, 9, and 12 months, using simulations by the mother/experimenter and videos of crying and laughing infants. Diagnosis was determined between 18 and 36 months. Infants later diagnosed with ASD showed a reduced empathic response toward a person simulating distress, but not toward a video of a crying peer, and not in response to others' joy (either in simulation or video). Overall, reduced empathic concern during the first year of life appears to be an early prodromal marker of subsequent ASD. Implications for theory, research, and practice are discussed.

Neurodevelopmental disorders in children born to mothers involved in maternal motor vehicle crashes.

To evaluate the association between maternal MVCs during pregnancy and neurodevelopmental disorders (NDDs, including intellectual disability, ADHD, ASD, and infantile cerebral palsy) in children. This population-based cohort of live births in Taiwan was analyzed, comparing children born to mothers involved in MVCs during pregnancy with those without such exposure. Children were linked to the insurance database to identify the possible diagnosis of NDDs. The Cox proportional hazards regression model was used to estimate the relative hazards. A total of 19,277 children with maternal MVCs and 76,015 children without exposure were included. Children exposed to maternal MVCs during the first two trimesters or whose mothers sustained mild to severe injuries showed a higher risk of intellectual disability. Severe maternal injuries also increased the risk of infantile cerebral palsy (aHR = 3.86; 1.27-11.78). MVCs in the third trimester, or mild maternal injuries, were associated with a higher risk of ASD (third trimester: aHR = 1.40; 1.04-1.87; mild injuries: aHR = 1.38; 1.09-1.74). Children exposed to maternal MVCs with severe injuries had a higher risk of intellectual disability and cerebral palsy. Third-trimester exposure may increase the risk of ASD. However, these findings should be interpreted cautiously as genetic factors may contribute to the observed association. There is some evidence linking maternal MVCs during pregnancy to the development of neurodevelopmental disorders in children. Children of mothers with severely injured were more likely to suffer from infantile cerebral palsy and intellectual disability. The risk of autism spectrum disorder is higher in children whose mothers are involved in MVCs during the late stage of pregnancy, and there is also an increased risk of intellectual disability during the first two trimesters.

EphB2 Signaling Is Implicated in Astrocyte-Mediated Parvalbumin Inhibitory Synapse Development.

Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch-clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice. While inhibitory synapse development is adversely affected by PV-specific expression of EphB2, a strong candidate ASD risk gene, astrocytic ephrin-B1 facilitates PV→PC connectivity through a mechanism involving EphB signaling in PV boutons. In contrast, the loss of astrocytic ephrin-B1 reduces PV→PC connectivity and inhibition, resulting in increased seizure susceptibility and an ASD-like phenotype. Our findings underscore the crucial role of astrocytes in regulating inhibitory circuit development and discover a new role of EphB2 receptors in PV-specific inhibitory synapse development.

A scalable, high-throughput neural development platform identifies shared impact of ASD genes on cell fate and differentiation.

Deleterious mutations in hundreds of genes confer high risk for neurodevelopmental disorders (NDDs), posing significant challenges for therapeutic development. Identifying convergent pathways shared across NDD genes could reveal high-impact therapeutic targets. To identity convergent pathways in NDD genes, we optimized Perturb-seq, a method combining CRISPR perturbation with single-cell RNA sequencing (scRNA-seq), and applied structural topic modeling (STM) to simultaneously assess impact on cell fate and developmental stage. We then studied a subset of autism spectrum disorder (ASD) genes implicated in regulation of gene expression using these improved molecular and analytical approaches. Results from targeting 60 high-confidence ASD risk genes revealed significant effects on neural development. As expected, ASD risk genes impacted both progenitor fate and/or neuronal differentiation. Using STM, we could identify latent topics jointly capturing cell types, cell fate, and differentiation stages. Repression of ASD risk genes led to changes in topic proportions and effects of four genes (DEAF1, KMT2A, MED13L, and MYT1L) were validated in an independent dataset. Our optimized Perturb-seq method, combined with a novel analytical approach, provides a powerful, cost-effective framework for uncovering convergent mechanisms among genes involved in complex neurodevelopmental processes. Application of these methods advanced understanding of the impact of ASD mutations on multiple dimensions of neural development, and provides a framework for a broader examination of the function of NDD risk genes.

Alterations in microbiota-metabolism-circRNA crosstalk in autism spectrum disorder-like behaviours caused by maternal exposure to glyphosate-based herbicides in mice

Epidemiological evidence indicates exposure to glyphosate-based herbicides (GBHs) increases the risk for autism spectrum disorder (ASD). The gut microbiota has been found to influence ASD behaviours through the microbiota-gut-brain axis. However, the underlying links between early life GBH exposure and ASD-like phenotypes through the microbiota-gut-brain axis remain unclear. Therefore, we exposed mice to low-dose GBH (0.10, 0.25, 0.50, and 1.00 %) and determined the effects on ASD-like behaviours. Furthermore, three kinds of omics (gut microbiomics, metabolomics, and transcriptomics) were conducted to investigate the effects of GBH exposure on gut microbiota, gut metabolites, and circular RNAs (circRNAs) in the prefrontal cortex (PFC) using a cross-generational mouse model. Behavioural analyses suggested social impairment and repetitive/stereotypic behaviours in the GBH-exposed offspring. Furthermore, maternal exposure to glyphosate significantly altered the ASD-associated gut microbiota of offspring, and ASD-associated gut metabolites were identified. Specifically, we found that alterations in the gut microenvironment may contribute to changes in gut permeability and the blood-brain barrier, which are related to changes in the levels of circRNAs in the PFC. Our results suggest a potential effect of circRNAs through the disruption of the gut-brain interaction, which is an important factor in the pathogenesis of ASD in offspring induced by maternal exposure to GBH.

Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements

CRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive cis-regulatory elements and the gene(s) they regulate. Random combinations of many gRNAs are introduced to each of many cells, which are then profiled and partitioned into test and control groups to test for effect(s) of CRISPRa perturbations of both enhancers and promoters on the expression of neighboring genes. Applying this method to a library of 493 gRNAs targeting candidate cis-regulatory elements in both K562 cells and iPSC-derived excitatory neurons, we identify gRNAs capable of specifically upregulating intended target genes and no other neighboring genes within 1 Mb, including gRNAs yielding upregulation of six autism spectrum disorder (ASD) and neurodevelopmental disorder (NDD) risk genes in neurons. A consistent pattern is that the responsiveness of individual enhancers to CRISPRa is restricted by cell type, implying a dependency on either chromatin landscape and/or additional trans-acting factors for successful gene activation. The approach outlined here may facilitate large-scale screens for gRNAs that activate genes in a cell type-specific manner.

HLA-A, -B, -C and -DRB1 Association with Autism Spectrum Disorder Risk: A Sex-Related Analysis in Italian ASD Children and Their Siblings.

Autism Spectrum disorders (ASD) are diagnosed more often in males than in females, by a ratio of about 3:1; this is likely to be due to a difference in risk burden between the sexes and/or to "compensatory skills" in females, that may delay the diagnosis of ASD. Identifying specific risk factors for ASD in females may be important in facilitating early diagnosis. We investigated whether HLA- class I: -A, -B, -C and class II -DRB1 alleles, which have been suggested to play a role in the development of ASD, can be considered as sex-related risk/protective markers towards the ASD. We performed HLA allele genotyping in 178 Italian children with ASD, 94 healthy siblings, and their parents. HLA allele distribution was compared between children with ASD, sex-matched healthy siblings, and a cohort of healthy controls (HC) enrolled in the Italian bone marrow donor registry. Allele transmission from parents to children with ASD and their siblings was also assessed. Our findings suggest that HLA-A*02, B*38, and C*12 alleles are more frequently carried by females with ASD compared to both HC and healthy female siblings, indicating these alleles as potential risk factors for ASD in females. Conversely, the HLA-A*03 allele was more commonly transmitted to healthy female siblings, suggesting it might have a protective effect. Additionally, the HLA-B*44 allele was found to be more prevalent in boys with ASD, indicating it is a potential risk factor for male patients. This is the first Italian study of sex-related HLA association with ASD. If confirmed, these results could facilitate early ASD diagnosis in female patients, allowing earlier interventions, which are crucial in the management of neurodevelopmental disorders.

Congenital hypothyroidism and risk of subsequent autism spectrum disorder and attention-deficit/hyperactivity disorder in Taiwan.

Evidence suggests an association between maternal hypothyroidism and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in offspring. We examined the risk of ASD and ADHD in individuals with congenital hypothyroidism (CHT). A nationwide population-based cohort study enrolled a total of 1260 children younger than 12 years with a confirmed diagnosis of CHT and no prior diagnosis of any neurodevelopmental disorders, selected from the National Health Insurance Research Database of Taiwan between 1998 to 2013. In addition, 12,600 controls matched for sex, age, and residence were selected. Cox proportional hazards analysis was used to investigate the association among CHT, ASD, and ADHD. Children with CHT were associated with a higher incidence of ASD (7.1‰ vs 1.3‰, P < 0.001) and ADHD (39.7‰ vs 18.7‰, P < 0.001) than the control group. Cox regression analyses demonstrated that children with CHT were associated with elevated risks of ASD (hazard ratio [HR], 4.72 [95% confidence interval (CI), 2.08-10.70]) and ADHD (HR, 2.03 [95% CI, 1.49-2.77]), after adjusting for demographic data and family history of major psychiatric disorders, compared with the control group. Children with CHT were associated with approximately a two-fold increased risk of ADHD and a four-fold increased risk of ASD than the control group. Our study highlights the need for future research to elucidate the potential pathophysiology among CHD, ASD, and ADHD.

Causal association between mitochondrial function and psychiatric disorders: Insights from a bidirectional two-sample Mendelian randomization study

BackgroundPrevious observational studies have suggested that there appears to be a close association between mitochondrial function and psychiatric disorders, but whether a causal role exists remains unclear. MethodsWe extracted genetic instruments for 67 mitochondrial-related proteins and 10 psychiatric disorders from publicly available genome-wide association studies, and employed five distinct MR methods and false discovery rate correction to detect causal associations between them. Additionally, we conducted a series of sensitivity tests and additional model analysis to ensure the robustness of the results. For potential causal associations, we further performed reverse MR analyses to assess the impact of reverse causality. ResultsWe identified a total of 2 significant causal associations and 24 suggestive causal associations. Specifically, Phenylalanine-tRNA ligase was found to increase the risk of Alzheimer's disease, while Mitochondrial glutamate carrier 2 decreased the risk of autism spectrum disorder. Furthermore, there was no evidence of significant pleiotropy, heterogeneity, or reverse causality. LimitationsThis study was limited to individuals of European ancestry, and the conclusions drawn are merely revelatory. ConclusionThis study provides novel insights into the relationship between mitochondria and psychiatric disorders, as well as the pathogenesis and treatment strategies for psychiatric disorders.

Modification and Validation of an Autism Observational Assessment Including ADOS-2® for Use with Children with Visual Impairment.

Children with visual impairment (VI) are at risk of autism spectrum disorder (ASD); however standard observational diagnostic assessments are not validated for this population. The primary objective of the study is to validate a modified version of the Autism Diagnostic Observation Schedule (ADOS-2®, Module 3), for children with VI. A cross-sectional observational study was undertaken with 100 (mean 5½ years, SD 10.44 months, range 4-7 years; 59 (59%) males) children with congenital disorders of the peripheral visual system with moderate/severe-profound VI. As the primary objective, 83 (83%) who were 'verbally fluent' were assessed with the modified ADOS-2® (Module 3). Their scores were investigated for reliability, construct and criterion validity against expert clinician formulation and parent-rated social and communication questionnaires (Social Responsiveness Scale-2, SRS-2; Children's Communication Checklist-2). The secondary objective with the total sample was to report on frequency and distribution of ASD ratings in this VI population. The modified ADOS-2® (Module 3) was found to have strong internal coherence and construct validity (two factor model) and inter-rater reliability. A new VI diagnostic algorithm was established which showed high sensitivity and specificity against clinician formulation. Using the best cut-off threshold for 'High Risk for ASD', strong concurrent criterion validity was found according to parent-rated scores on the SRS-2. The modified ADOS-2® (Module 3) was shown to have promising reliability and validity in establishing children at 'High Risk of ASD' in this vulnerable population. Elevated rates of ASD were found across the sample, in line with previous estimates.

Risk of psychiatric neurodevelopmental disorders after meningitis in childhood: a nationwide, population-based cohort study.

Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis. Nationwide population-based cohort study (Denmark, 1995-2021) of children with positive cerebrospinal fluid for bacteria or enterovirus, stratified on age as young infants (0 to <90 days, n = 637) or older children (≥90 days to <17 years, n = 1,218). We constructed a comparison cohort from the general population (n = 18,550), and cohorts of siblings of participants. As risk estimates of PNDD we calculated age- and sex-adjusted hazard ratios (aHRs) with 95% confidence intervals (95%CI). Children with bacterial meningitis had increased risks of PNDD, especially learning and intellectual developmental disorders (young infants: aHR 4.2, 95%CI: 2.4-7.1; older children: aHR 1.5, 95%CI: 1.0-2.3), attention deficit disorder (ADHD) (young infants: aHR 2.8, 95%CI: 1.5-5.2; older children: 1.4, 95%CI: 0.9-2.2) and redemption of ADHD medication (young infants: aHR 2.2, 95%CI: 1.0-4.7; older children: 1.5, 95%CI: 1.0-2.3). Young infants with bacterial meningitis additionally had increased risks of autism spectrum disorders (aHR 1.9, 95%CI: 0.9-4.1) and behavioural and emotional disorders (aHR 2.0, 95%CI: 1.0-3.9). In young infants, the excess risk of PNDD was especially observed in premature children. Siblings of older children with bacterial meningitis also had increased risks of PNDD. Children with enteroviral meningitis at any age did not have increased risks of PNDD or redemption of ADHD medication. Bacterial meningitis in childhood is associated with subsequent diagnosis of PNDD, while enteroviral meningitis is not. The association appears to be partly explained by prematurity and familial and socioeconomic factors.

HCBiLSTM-WOA: hybrid convolutional bidirectional long short-term memory with water optimization algorithm for autism spectrum disorder

Autism Spectrum Disorder (ASD) is a type of brain developmental disability that cannot be completely treated, but its impact can be reduced through early interventions. Early identification of neurological disorders will better assist in preserving the subjects’ physical and mental health. Although numerous research works exist for detecting autism spectrum disorder, they are cumbersome and insufficient for dealing with real-time datasets. Therefore, to address these issues, this paper proposes an ASD detection mechanism using a novel Hybrid Convolutional Bidirectional Long Short-Term Memory based Water Optimization Algorithm (HCBiLSTM-WOA). The prediction efficiency of the proposed HCBiLSTM-WOA method is investigated using real-time ASD datasets containing both ASD and non-ASD data from toddlers, children, adolescents, and adults. The inconsistent and incomplete representations of the raw ASD dataset are modified using preprocessing procedures such as handling missing values, predicting outliers, data discretization, and data reduction. The preprocessed data obtained is then fed into the proposed HCBiLSTM-WOA classification model to effectively predict the non-ASD and ASD classes. The initially randomly initialized hyperparameters of the HCBiLSTM model are adjusted and tuned using the water optimization algorithm (WOA) to increase the prediction accuracy of ASD. After detecting non-ASD and ASD classes, the HCBiLSTM-WOA method further classifies the ASD cases into respective stages based on the autistic traits observed in toddlers, children, adolescents, and adults. Also, the ethical considerations that should be taken into account when campaign ASD risk communication are complex due to the data privacy and unpredictability surrounding ASD risk factors. The fusion of sophisticated deep learning techniques with an optimization algorithm presents a promising framework for ASD diagnosis. This innovative approach shows potential in effectively managing intricate ASD data, enhancing diagnostic precision, and improving result interpretation. Consequently, it offers clinicians a tool for early and precise detection, allowing for timely intervention in ASD cases. Moreover, the performance of the proposed HCBiLSTM-WOA method is evaluated using various performance indicators such as accuracy, kappa statistics, sensitivity, specificity, log loss, and Area Under the Receiver Operating Characteristics (AUROC). The simulation results reveal the superiority of the proposed HCBiLSTM-WOA method in detecting ASD compared to other existing methods. The proposed method achieves a higher ASD prediction accuracy of about 98.53% than the other methods being compared.

Genetic and environmental risk factors in autistic children

A complex neurodevelopmental disorder known as autism spectrum disorder (ASD) is characterized by difficulties with behavior, socialization, and communication. ASD has a complex etiology, with environmental and genetic variables playing a role in its development. The purpose of this research is to assess our current knowledge of the genetic predispositions and environmental exposures that raise a child's risk of autism spectrum disorder (ASD). To find important risk variables, we examined data from several epidemiological studies, genome-wide association studies (GWAS), and environmental health studies. Our results demonstrate the significant contribution that genetic mutations both inherited and de novo make to the increased risk of ASD. Critical environmental factors that we also discovered were maternal illnesses, prenatal pollution exposure, and dietary deficits. This integrated method emphasizes how important it is to take into account both environmental and genetic elements in order to better understand and maybe lower the risk of ASD.

Impact of KDM6B mosaic brain knockout on synaptic function and behavior

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.

Impacts of PFAS Exposure on Neurodevelopment: A Comprehensive Literature Review

Neurodevelopmental disorders (NDDs) encompass a range of conditions that begin during the developmental stage and cause deficits that lead to disruptions in normal functioning. One class of chemicals that is of increasing concern for neurodevelopmental disorders is made up of per- and polyfluoroalkyl substances (PFAS). In this comprehensive literature review, we investigated data from epidemiological studies to understand the connection between PFAS exposure and neurodevelopmental endpoints such as cognitive function, intelligence (IQ), and memory, along with behavioral changes like Attention-Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD). When we reviewed the findings from individual studies that analyzed PFAS levels in biological samples and their association with NDD, we concluded that there was a correlation between PFAS and neurodevelopmental disorders. The findings suggest that children exposed to higher PFAS levels could potentially have an increased risk of ASD and ADHD along with an inhibitory effect on IQ. While the results vary from one study to another, there is increasing association between PFAS exposure and neurodevelopmental disorders. Importantly, the findings provide valuable insights into the adverse effects associated with PFAS exposure and neurodevelopment.

Association between blood mitochondrial DNA copy number and mental disorders: A bidirectional two-sample mendelian randomization study

BackgroundMitochondria is essential for cellular energy production, oxidative stress, and apoptosis. Mitochondrial DNA (mtDNA) encodes essential proteins for mitochondrial function. Although several studies have explored the association between changes in mtDNA copy number (mtDNA-CN) and risk of mental disorders, the results remain debated. This study used a bidirectional two-sample Mendelian randomization (MR) analysis to examine the genetic causality between mtDNA-CN and mental disorders. MethodsGenome-wide association study (GWAS) data for mtDNA-CN were sourced from UK biobank, involving 383,476 European cases. GWAS data for seven mental disorders—attention deficit/hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia, bipolar disorder, major depressive disorder, anxiety, and obsessive-compulsive disorder—were primarily obtained from the Psychiatric Genomics Consortium. Causal associations were assessed using inverse variance weighting, with sensitivity analyses via the weighted median and MR-Egger methods. Reverse MR considered the seven mental disorders as exposures. All analyses were replicated with additional mtDNA-CN GWAS data from 465,809 individuals in the Heart and Ageing Research in Genomic Epidemiology consortium and the UK Biobank. ResultsForward MR observed a 27 % decrease in the risk of ASD per standard deviation increase in genetically determined blood mtDNA-CN (OR = 0.73, 95%CI: 0.58–0.92, p = 0.002), with no causal effects on other disorders. Additionally, reverse MR did not indicate a causal association between any of the mental disorders and mtDNA-CN. Validation analyses corroborated these findings, indicating their robustness. ConclusionsOur study supports the potential causal association between mtDNA-CN and the risk of ASD, suggesting that mtDNA-CN could serve as a promising biomarker for early screening of ASD.

Dynamic convergence of autism disorder risk genes across neurodevelopment.

Over a hundred risk genes underlie risk for autism spectrum disorder (ASD) but the extent to which they converge on shared downstream targets to increase ASD risk is unknown. To test the hypothesis that cellular context impacts the nature of convergence, here we apply a pooled CRISPR approach to target 29 ASD loss-of-function genes in human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells, glutamatergic neurons, and GABAergic neurons. Two distinct approaches (gene-level and network-level analyses) demonstrate that convergence is greatest in mature glutamatergic neurons. Convergent effects are dynamic, varying in strength, composition, and biological role between cell types, increasing with functional similarity of the ASD genes examined, and driven by cell-type-specific gene co-expression patterns. Stratification of ASD genes yield targeted drug predictions capable of reversing gene-specific convergent signatures in human cells and ASD-related behaviors in zebrafish. Altogether, convergent networks downstream of ASD risk genes represent novel points of individualized therapeutic intervention.

Examining the association between autism spectrum disorder and atopic eczema: meta-analysis of current evidence.

This study aims to investigate the association between autism spectrum disorder (ASD) and atopic eczema (AE), shedding light on potential associations and underlying mechanisms. A comprehensive review of literature was conducted to identify relevant studies published up to August 2023. Various electronic databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched using specific keywords related to ASD and AE. The meta-analysis covered a total of 30 studies. The first analysis included 23 studies with a combined total of 147430 eczema patients in the ASD group and 8895446 eczema patients in non-ASD group. We calculated the risk ratio of eczema in ASD and non-ASD groups, which revealed a significantly higher risk of eczema in patients with ASD (RR 1.34; 95% CI 1.03, 1.76). The second analysis included seven studies with a combined total of 3570449 ASD patients in the AE group and 3253973 in the non-Eczema group. The risk ratio of ASD in the Eczema and Non-Eczema groups showed a significantly increased risk of ASD in patients with eczema (RR 1.67; 95% CI 0.91, 3.06). This study underscores the possible link between ASD and atopic eczema, shedding light on their potential association. Our study conducted a meta-analysis on the association between autism spectrum disorder (ASD) and atopic eczema (AE), shedding light on potential associations and underlying mechanisms. The review we conducted covered a total of 30 studies. This study underscores the possible link between ASD and atopic eczema, shedding light on their potential association.