Autism Spectrum Disorder Risk Research Articles

Maternal diabetes during pregnancy and offspring's risk of autism spectrum disorder: A systematic review and meta-analysis.

Whether in utero exposure to pregestational (type 2 [T2D] and type 1 diabetes [T1D]) and gestational diabetes (GDM) are contributing factors in the rise of neurodevelopmental alterations such as autism is yet unclear. Therefore, we summarized the evidence from studies that assessed such association. A systematic review with meta-analyses was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines; eligible studies were identified in PubMed, Web of Science, and EBSCO up to April 3rd, 2023. We estimated pooled OR of autism from random effects meta-analyses for each type of maternal diabetes. 26 publications were selected (18 cohorts and 8 case-controls); 17 had data for the meta-analysis. We observed an increased risk of autism in the offspring exposed in utero to T2D (pooled OR=1.48; 95%CI: 1.31, 1.68; n=3,141,255), T1D (pooled OR=1.73; 95%CI: 1.05, 2.87; n=2,791,607), and GDM (pooled OR=1.31; 95% CI: 1.16, 1.47; n=3,259,557) compared to those unexposed. No evidence of heterogeneity (I2=0.0%) was observed for T2D, whereas for T1D the heterogeneity was substantial (I2=64.7%) and for GDM was moderate (I2=53.1%). The evidence was stronger for in utero exposure to GDM, followed by T2D and T1D. Our results support the hypothesis that in utero exposure to maternal T2D or GDM moderately increased the offspring's risk of developing autism later in life. Prospectively conducted studies are still warranted to better estimate the size of the effect of maternal diabetes on autism risk.

Developing a simplified measure to predict the risk of autism spectrum disorders: Abbreviating the M-CHAT-R using a machine learning approach in China.

Early screening for autism spectrum disorder (ASD) is crucial, yet current assessment tools in Chinese primary child care are limited in efficacy. This study aims to employ machine learning algorithms to identify key indicators from the 20-item Modified Checklist for Autism in Toddlers, revised (M-CHAT-R) combining with ASD-related sociodemographic and environmental factors, to distinguish ASD from typically developing children. Data from our prior validation study of the Chinese M-CHAT-R (August 2016-March 2017, n = 6,049 toddlers) were reviewed. We extracted the 20-item M-CHAT-R data and integrated 17 sociodemographic and environmental risk factors associated with ASD development to strengthen M-CHAT-R's machine learning screening. Five feature selection methods were used to extract subsets from the original set. Six machine learning algorithms were applied to identify the optimal subset distinguishing clinically diagnosed ASD toddlers from typically developing toddlers. Nine features were grouped into three subsets: subset 1 contained unanimously recommended items (A1 [Follows point], A3 [Pretend play], A9 [Brings objects to show], A10 [Response to name] and A16 [Gazing following]). Subset 2 added two items (A17 [Gaining parent's attention] and A18 [Understands what is said]), and subset 3 included two more items (A8 [Interest in other children] and child's age). The top-performing algorithm resulted in a seven-item classifier of subset 2 with 92.5 % sensitivity, 90.1 % specificity, and 10.0 % positive predictive value. Machine learning classifiers effectively differentiate ASD toddlers from typically developing toddlers using a reduced M-CHAT-R item set. This highlights the clinical significance of machine learning-optimized models for ASD screening in primary health care centers and broader applications.

Acetaminophen in Pregnancy and Attention-Deficit and Hyperactivity Disorder and Autism Spectrum Disorder.

Acetaminophen is a common over-the-counter medication that recently gained substantial media attention regarding its use by pregnant individuals. In this clinical perspective, we discuss the strengths and limitations of the published literature on the effect of maternal acetaminophen use in pregnancy on the child's risk of developing attention-deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Studies included were specifically selected on the basis of the quality and validity of ADHD or ASD outcome definitions. From a total of 56 identified studies, commentaries, and editorials of relevance, we critically reviewed nine studies with original data that satisfied our inclusion criteria and three meta-analyses. Most studies that have reported positive findings are difficult to interpret because they have important biases, notably a high degree of selection bias, variability in selection and adjustment for various potential confounders, and unmeasured familial confounding. When unobserved familial confounding through sibling analysis was controlled for, associations weakened substantially. This suggests that residual confounding from shared genetic and environmental factors may have caused an upward bias in the original observations. According to the current scientific evidence, in utero exposure to acetaminophen is unlikely to confer a clinically important increased risk of childhood ADHD or ASD. The current level of evidence does not warrant changes to clinical guidelines on the treatment of fever or pain in pregnancy. Prospective research designed to account for familial and psychosocial environmental factors related to both maternal use of acetaminophen and children's neurodevelopment should be undertaken.

Causal associations between iron levels in subcortical brain regions and psychiatric disorders: a Mendelian randomization study

Despite observational studies linking brain iron levels to psychiatric disorders, the exact causal relationship remains poorly understood. This study aims to examine the relationship between iron levels in specific subcortical brain regions and the risk of psychiatric disorders. Utilizing two-sample Mendelian randomization (MR) analysis, this study investigates the causal associations between iron level changes in 16 subcortical nuclei and eight major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and insomnia. The genetic instrumental variables linked to iron levels and psychiatric disorders were derived from the genome-wide association studies data of the UK Biobank Brain Imaging and Psychiatric Genomics Consortium. Bidirectional causal estimation was primarily obtained using the inverse variance weighting (IVW) method. Iron levels in the left substantia nigra showed a negative association with the risk of MDD (ORIVW = 0.94, 95% CI = 0.91–0.97, p < 0.001) and trends with risk of SCZ (ORIVW = 0.90, 95% CI = 0.82–0.98, p = 0.020). Conversely, iron levels in the left putamen were positively associated with the risk of ASD (ORIVW = 1.11, 95% CI = 1.04–1.19, p = 0.002). Additionally, several bidirectional trends were observed between subcortical iron levels and the risk for psychiatric disorders. Lower iron levels in the left substantia nigra may increase the risk of MDD, and potentially increase the risk of SCZ, indicating a potential shared pathogenic mechanism. Higher iron levels in the left putamen may lead to the development of ASD. The observed bidirectional trends between subcortical iron levels and psychiatric disorders, indicate the importance of the underlying biomechanical interactions between brain iron regulation and these disorders.

Genetic and Environmental Influences on Autism Spectrum Disorder: A Multi-Center Study Exploring Gene-Environment Interactions and Biomarkers in Indonesia

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex etiology involving genetic and environmental factors. This multi-center study investigated gene-environment interactions and potential biomarkers associated with ASD in the Indonesian population. Methods: Children diagnosed with ASD (n=500) and age-matched typically developing controls (n=500) were recruited across five major Indonesian cities. Whole-exome sequencing targeted genotyping, and environmental risk factor assessments were conducted. Biomarker analyses included cytokine levels, oxidative stress markers, and neurotransmitters. Results: Genetic analysis revealed both rare and common variants associated with ASD risk, including variants in CHD8, SCN2A, NRXN1, and novel genes. Prenatal exposures (maternal medication use, infections), perinatal complications (preterm birth, low birth weight), and postnatal factors (pesticide exposure, air pollution) were associated with increased ASD risk. Children with ASD exhibited elevated inflammatory markers (TNF-α, IL-6, IL-1β), increased oxidative stress (higher MDA, lower GSH), and altered neurotransmitter levels (lower serotonin and dopamine) compared to controls. Conclusion: This study provides insights into the interplay of genetic and environmental factors contributing to ASD risk in Indonesia. The identified genetic variants, environmental risk factors, and potential biomarkers may contribute to our understanding of ASD etiology and inform the development of targeted interventions and early detection strategies.

Examining the Prevalence, Characteristics, and Potential Links Between Skin Disorders and Autism Spectrum Disorder (ASD).

Background: Increasing evidence indicates that skin disorders may contribute to an increased risk of autism spectrum disorder (ASD). They can affect the quality of life, and they have an impact on social isolation, behavioral problems, cognitive scores, and some subscales of ASD. Methods: This study was an online questionnaire-based, observational, and cross-sectional study conducted during the period from August 2022 through January 2023 to examine dermatological manifestations among ASD individuals compared to controls. Descriptive and non-parametric tests were used for data analysis. Results: A total of 363 individuals with skin diseases were interviewed during the study period. In total, 189 (52.1%) of participants were autistic and 174 (47.9%) were controls. Asthma, anxiety, depression, and autoimmune disease were persistent in the ASD group compared to the controls (p < 0.001). The results also show that skin, food, and respiratory allergies were statistically significantly associated with ASD (50%, 22.2%, 14.8%, respectively) compared to the controls (26.4%, 10.3%, 7.5%, respectively) (p < 0.05). The most prevalent disease in the controls was eczema (15.5%), followed by dry skin (14.9%) and acne (10.3%). These diseases showed a statistically significant association with ASD compared to the controls (p < 0.0001). Conclusions: Our findings indicate that atopic disorders and comorbidities, including eczema, asthma, and allergies, are significantly associated with ASD. A large population-based study is warranted to clarify the prevalence of skin disorders among individuals with ASD, coupled with the study of the association between skin disorders and comorbidities to determine the relationship precisely.

The zinc-finger protein POGZ associates with Polycomb repressive complex 1 to regulate bone morphogenetic protein signaling during neuronal differentiation.

Polycomb Repressive Complex 1 (PRC1) is a family of epigenetic regulators critical for mammalian development. Elucidating PRC1 composition and function across cell types and developmental stages is key to understanding the epigenetic regulation of cell fate determination. In this study, we discovered POGZ, a prominent Autism Spectrum Disorder (ASD) risk factor, as a novel component of PRC1.6, forming the PRC1.6-POGZ complex. Functional assays revealed that POGZ elicits transcriptional repression that is dependent on RING1B expression. Analysis of publicly available ChIP-Seq data showed that POGZ highly colocalizes with RING1B and HP1γ, two PRC1.6 components, at genes involved in multiple aspects of transcriptional regulation in the embryonic mouse cortex. Although Pogz knockout (KO) does not compromise stem cell pluripotency, Pogz ablation in neuronal progenitor cells (NPCs) led to widespread transcriptomic dysregulation with failed activation of key neuronal genes. Finally, we demonstrated that PRC1.6-POGZ regulates neuronal differentiation by repressing the bone morphogenetic protein (BMP) signaling pathway. These findings reveal a mechanism by which PRC1 and POGZ coordinate transcriptional regulation during neuronal differentiation, which offers insights into how disruptions in this pathway may contribute to neurodevelopmental disorders such as ASD.

Deleterious coding variation associated with autism is consistent across populations, as exemplified by admixed Latin American populations.

Branko Aleksic, Mykyta Artomov, Mafalda Barbosa, Elisa Benetti, Catalina Betancur, Monica Biscaldi-Schafer, Anders D. Børglum, Harrison Brand, Alfredo Brusco, Joseph D. Buxbaum, Gabriele Campos, Simona Cardaropoli, Diana Carli, Angel Carracedo, Marcus C. Y. Chan, Andreas G. Chiocchetti, Brian H. Y. Chung, Brett Collins, Ryan L. Collins, Edwin H. Cook, Hilary Coon, Claudia I. S. Costa, Michael L. Cuccaro, David J. Cutler, Mark J. Daly, Silvia De Rubeis, Bernie Devlin, Ryan N. Doan, Enrico Domenici, Shan Dong, Chiara Fallerini, Magdalena Fernandez, Montserrat Fernández-Prieto, Giovanni Battista Ferrero, Eugenio Ferro, Jennifer Foss Feig, Christine M. Freitag, Jack M. Fu, Liliana Galeano, J. Jay Gargus, Sherif Gerges, Elisa Giorgio, Ana Cristina Girardi, Stephen Guter, Emily Hansen-Kiss, Erina Hara, Danielle Halpern, Gail E. Herman, Luis C. Hernandez, Irva Hertz-Picciotto, David M. Hougaard, Christina M. Hultman, Suma Jacob, Miia Kaartinen, Lambertus Klei, Alexander Kolevzon, Itaru Kushima, Maria C. Lattig, So Lun Lee, Terho Lehtimäki, Lindsay Liang, Carla Lintas, Alicia Ljungdahl, Andrea del Pilar Lopez, Caterina Lo Rizzo, Yunin Ludena, Patricia Maciel, Behrang Mahjani, Nell Maltman, Marianna Manara, Dara S. Manoach, Dalia Marquez, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Matthew Mosconi, Marina Natividad Avila, Rachel Nguyen, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Lisa Pavinato, Katherine P. Peña, Minshi Peng, Margaret Pericak-Vance, Antonio M. Persico, Isaac N. Pessah, Thariana Pichardo, Kaija Puura, Abraham Reichenberg, Alessandra Renieri, Kathryn Roeder, Catherine Sancimino, Stephan J. Sanders, Sven Sandin, F. Kyle Satterstrom, Stephen W. Scherer, Sabine Schlitt, Rebecca J. Schmidt, Lauren Schmitt, Katja Schneider-Momm, Paige M. Siper, Laura Sloofman, Moyra Smith, Renee Soufer, Christine R. Stevens, Pål Suren, James S. Sutcliffe, John A. Sweeney, Michael E. Talkowski, Flora Tassone, Karoline Teufel, Elisabetta Trabetti, Slavica Trajkova, Maria del Pilar Trelles, Brie Wamsley, Jaqueline Y. T. Wang, Lauren A. Weiss, Mullin H. C. Yu, Ryan Yuen, Jessica Zweifach.

Maternal Cannabis Use During Pregnancy and Neuropsychiatric Adverse Outcomes During Childhood and Early Adult Life.

Cannabis use during pregnancy is increasing; the study of adverse outcomes in cannabis-exposed pregnancies is therefore important. Previous articles in this series described increased risks of maternal adverse outcomes, fetal adverse outcomes, birth defects in newborns, and autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in childhood. This article examines neuropsychiatric adverse outcomes in offspring gestationally exposed to cannabis. Currently available research suggests that prenatal cannabis exposure is associated with increased risks of ASD, ADHD, psychosis proneness, psychotic like experiences, internalizing problems, externalizing problems, attention problems, thought-related problems, social problems, impaired executive function, and observed aggression. There is insufficient study of prenatal cannabis exposure and offspring IQ. Shortcomings in the existing literature are discussed; as examples, many outcomes were determined by screening rather than by formal assessment, prenatal cannabis exposure was ascertained retrospectively in some studies, childhood adverse experiences and exposures were seldom included as covariates, and details about cannabis use (source, potency, frequency, reasons) were unavailable. Curiously, the findings of adverse outcomes were inconsistent, and the effect sizes were small. Possible explanations are that women who use cannabis during pregnancy may not admit it and their pregnancy outcomes may then be misclassified into the control group, assessment of outcomes at too young an age or with insufficient accuracy may blur differences between exposed and unexposed groups, and adjustment for covariates may mask the full effects of cannabis. A last observation is that the studies reviewed were based on exposures that occurred decades ago. Given the increasing potency of currently available cannabis and the limitations of the existing research, it is possible that the available findings underestimate the breadth and severity of the risks. Cannabis is not a necessary substance for use during pregnancy, and so women who consider it safe might do well to guard against complacency and unnecessary exposure.

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

Background Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis. Methods 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). Results 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. Conclusions 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.

Sociocultural and perinatal health factors associated with Autism spectrum disorder (ASD) in children.

While previous research has examined perinatal factors in the context of Autism Spectrum Disorder (ASD), studies focusing on sociocultural factors is limited. We conducted a cross-sectional analysis utilizing data from the Australian Autism Biobank (AAB), which encompasses autistic children aged 2-17, their siblings, parents, and unrelated controls. Employing multivariable regression analyses, we aimed to identify factors associated with ASD across various domains, spanning health and lifestyle, perinatal, and postnatal contexts. Importantly, our analyses were adjusted for critical sociodemographic covariates. Advanced maternal age, male sex at birth, and identifying as from culturally and linguistically diverse (CALD) background, were found to be associated with risk of ASD. Pre-existing chronic health conditions in both parents and paternal medication use before conception were also associated with ASD risk in children. Associations with complications during pregnancy, caesarean delivery, and maternal medication use during pregnancy were also found. Postnatal factors of interest included the presence of health conditions (e.g., epilepsy), infections in early-life (e.g., respiratory infections), and atypical development in the first six months of life (e.g., hypotonia). These insights can guide closer monitoring and support for those with pre-existing vulnerabilities especially in terms of certain perinatal and sociocultural characteristics.

Association Between Respiratory Infections and Risk of Autism Spectrum Disorder: An Overview

: Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder. Its incidence has dramatically risen during the last few decades. ASD is a multifactorial disorder. In addition to genetic factors, the environment plays a key role during critical periods of neurodevelopment. The prenatal environment, as well as perinatal and postnatal exposures to infection and inflammation, are increasingly identified as potential risk factors for autism and can influence development and increase neurodevelopmental disorders. Immune dysfunction and dysregulation are considered an important factor contributing to the pathogenesis of autism and may influence the course and severity of the disease. This study aims to analyze the data available in the scientific literature regarding the correlation between respiratory infections and autism.

Characteristics and outcomes of the screening program of autism spectrum disorder in Primary Healthcare Centers in Bahrain

Abstract: BACKGROUND: Autism spectrum disorder (ASD) is a chronic neurodevelopmental condition that requires early diagnosis and intervention for the improvement of the patient’s skills and functioning. Several guidelines, therefore, recommend the screening of all children for ASD. This study determined the outcomes of ASD screening program in Primary Healthcare Centers (PHCs) in Bahrain. MATERIALS AND METHODS: A cross-sectional study was conducted in 12 of the 27 PHCs in Bahrain. The Modified Checklist for Autism in Toddlers-Revised (MCHAT-R) was completed for children who attended the selected centers. Findings from the checklists and the outcome of positive screening cases were recorded. MCHAT-R scores of &lt;3 were indicative of a low risk for ASD. Children with moderate and high MCHAT-R risk were referred for psychiatric assessment. SPSS version 25.0 was used for data analysis; mean and standard deviation were calculated for continuous variables, and categorical variables presented as frequency and percentage. Chi-square test or Fisher’s exact test, as appropriate, used to test for statistical significance. RESULTS: A total of 3729 MCHAT-R checklists of children with a mean age of 2 years were included. Most children were Bahraini (78.0%), half of whom were males (51.3%). While most of the children (98.8%) had a low-risk MCHAT-R score, 1.2% had a moderate-high risk MCHAT score (12.33/1000). Of the cohort, 19 cases (0.51%) had ASD, 5.10/1000 children. Nearly two-thirds of children with confirmed ASD were males ( 63.2%), and one-third were females (36.8%). In addition, 14 cases (41.2%) of those who had moderate-high MCHAT refused to follow the subsequent diagnostic protocol. CONCLUSION: This study revealed a low prevalence of positive MCHAT-R screening and confirmed ASD cases. The vast majority of children who were positive on screening had a confirmed diagnosis of ASD. Some cases with positive MCHAT results failed to follow up for diagnosis. Therefore, improving parental and community awareness regarding ASD is important for a better outcome.

Different faces of autism: Patients with mutations in PTEN and FMR1 genes.

Autism spectrum disorder (ASD) is among the most common neurodevelopmental conditions in humans. While public awareness of the challenges faced by individuals with autism is steadily increasing, the underlying causes of abnormalities observed in ASD remains incompletely understood. The autism spectrum is notably broad, with symptoms that can manifest in various forms and degrees of severity. Core features of ASD, such as communication difficulties, impaired social interactions, and restricted patterns of behavior, interests, and activities, are often accompanied by other co‑occurring conditions, such as anxiety. ASD affects individuals regardless of gender, race, or ethnicity. Although we are currently unable to pinpoint a single definitive cause of autism, it is clear that genetics play a crucial role in its development. The first genes associated with an increased risk for ASD were discovered in rare monogenic disorders, such as fragile X syndrome (FXS), caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, and macrocephaly, linked to mutations in the phosphatase and tensin homolog (PTEN) gene. This review aims to summarize the current knowledge of ASD in patients with mutations in the FMR1 and PTEN genes.

Risk of autism spectrum disorder at 18 months of age is associated with prenatal level of polychlorinated biphenyls exposure in a Japanese birth cohort

Risk of autism spectrum disorder at 18 months of age is associated with prenatal level of polychlorinated biphenyls exposure in a Japanese birth cohort

The association between screen exposure and autism spectrum disorder in children: meta-analysis.

The goal is to provide light on the contentious relationship between screen exposure and childhood autism spectrum disorder (ASD). By conducting two meta-analyses that showed a potential association, including screen exposure effect by ASD and ASD risk by screen exposure, we aimed to clarify the potential causality between screen exposure and childhood ASD. The literature published up to December 2023 were systematically collected, and the combined effect values of weighted mean difference (WMD) and 95 % confidence interval (CI) and odds ratio (OR) and 95 % CI were calculated using two meta-analyses using the STATA 12.0. A total of 197,357 children, including 4,599 childhood ASD, were finally included in 10 studies. The results showed that children with ASD had higher levels of screen time exposure than healthy controls (combined effect value WMD=0.27, 95 % CI: 0.12-0.41, p<0.001). An increased risk of ASD was also found in children with high screen exposure compared to the low screen exposure group (OR=1.5395 % CI: 1.14-2.06). The development of childhood ASD may be associated with screen exposure. Future prospective studies are needed to verify the relationship between screen exposure and ASD in children.

Causal Relationship between Attention-Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Two-Sample Mendelian Randomization.

Aims/Background Despite the exponential increase in the incidence rate of Autism spectrum disorder (ASD), effective therapies for the disorder are still limited. According to vast clinical observations, the pathogeneses of ASD and Attention-deficit hyperactivity disorder (ADHD) share a great deal of similarities. This serves as a prompt to investigate, in this study, whether patients with ADHD are at a higher risk for ASD, which is significant for disease prevention. Methods Data concerning ADHD as the exposure variable and ASD as the outcome variable were collected from the publicly available Integrative Epidemiology Unit Open GWAS project (IEU GWAS) database. After screening the instrumental variables (IVs), statistical analysis was performed using the TwoSampleMR package of version R4.3.1, and sensitivity testing was conducted to evaluate the stability and reliability of the results. Results After screening the Single nucleotide polymorphisms (SNPs) through the calculation of F-value and Mendelian randomization (MR) Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), seven SNPs that satisfied the three major assumptions of Mendelian randomization were selected as IVs and could be used in place of ADHD in exploring the aforementioned causal relationship. The Odds ratio (OR) for the random-effect Inverse-variance weighted (IVW) method was 1.31 (95% Confidence interval [CI]: 1.14-1.52; p = 0.0001). A similar trend was observed for the Weighted median estimator (WME) method, with an OR of 1.37 (wider 95% CI: 1.15-1.64; p = 0.0005). Conclusion This study includes the pooled data on ADHD and ASD from the IEU GWAS public database, and there is sufficient evidence that patients with ADHD have a higher risk of ASD.

Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice.

Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring. We observed enhanced motor learning and earlier response times on an interval timing task, with accompanying changes in time-related medium spiny neuron (MSN) activity. We performed adult dorsal striatal single-cell RNA sequencing following prenatal stress which revealed differentially expressed genes (DEGs) in multiple cell types; downregulated DEGs were enriched for ribosome and translational pathways consistently in MSN subtypes, microglia, and somatostatin neurons. DEGs in MSN subtypes over-represented ASD risk genes and were enriched for synapse-related processes. These results provide insights into striatal alterations relevant to neurodevelopmental disorders.

Maternal Risk Factors for Autism Spectrum Disorder

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social communication, restricted interests, and repetitive behaviors. The etiology of ASD is multifactorial, involving genetic, environmental, and maternal factors. Recent studies have suggested maternal factors, such as advanced maternal age, high BMI, smoking, and depression during pregnancy, as significant risk factors for ASD. Objective: This study aims to investigate the maternal risk factors that contribute to ASD in children at Diyala, Iraq. Patients and Methods: This case-control study was conducted on 150 children, comprising 75 children diagnosed with ASD and 75 healthy children as a control group. The study was carried out from August 2023 to May 2024 in Diyala, Iraq. Data collection included comprehensive demographic, social, obstetric, and maternal health histories. ASD diagnosis was confirmed using the Childhood Autism Rating Scale 2 (CARS-2). A logistic regression analysis was performed to assess the association between maternal risk factors and ASD. Results: The study revealed several significant maternal risk factors for ASD. Advanced maternal age at pregnancy (mean age 28.1 years in cases vs. 22.9 years in controls, p=0.001), high maternal BMI (mean BMI 26.9 in cases vs. 24.4 in controls, p=0.0001), maternal smoking (6.7% in cases vs. 0% in controls, p=0.023), and maternal depression during pregnancy (22.7% in cases vs. 0% in controls, p=0.0001) were all significantly associated with an increased risk of ASD. The use of stimulating hormones before pregnancy also showed a significant association (21.3% in cases vs. 4% in controls, p=0.001). Parity, particularly having 1-2 pregnancies, was also a significant risk factor (p=0.002). Conclusion: This study identifies advanced maternal age, high BMI, smoking, depression, and the use of stimulating hormones before pregnancy as significant maternal risk factors for ASD in children. Keywords: Autism, ASD, maternal age and autism, maternal illness and autism.

Maternal Cannabis Use in Pregnancy and Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder in Offspring.

Up to 10% of women may use cannabis during pregnancy; this is of concern because constituents of cannabis cross the placental barrier and potentially influence neurodevelopment by acting on cannabinoid receptors in the developing fetal brain. In this context, a recent meta analysis of 13 observational studies found that gestational exposure to cannabis was associated with a small increase in the risk of autism spectrum disorder (ASD; relative risk [RR], 1.30) and with an even smaller increase in the risk of attention deficit/hyperactivity disorder (ADHD; RR, 1.13); the latter finding was probably supported by publication bias. In this meta-analysis, 4 studies provided information on ASD (pooled N = 178,565) and 10 on ADHD (pooled N = 203,783). In a large (n = 222,534) retrospectively ascertained cohort study published after the meta-analysis, cannabis use disorder (CUD) recorded before pregnancy, during pregnancy, and during pregnancy plus the year after delivery were associated with closely similar increased risks of ASD (RRs, 3.02-3.21). The risks were smaller in smokers (RRs, 1.74-1.87) than in nonsmokers (RRs, 4.55-4.83) but differed little between male (RRs, 3.01-3.06) and female (RRs, 2.71-2.85) offspring. Although the cohort study had many strengths, its limitations permitted only the conclusion that peri-pregnancy exposure to CUD is associated with a large increase in the risk of ASD in offspring; it remained possible that much of the risk was driven by genetic, environmental, or behavioral variables. The field is nascent; the total number of cannabis exposed pregnancies (with ASD and ADHD as the outcomes) in world literature is small. However, cannabis use during pregnancy is, at the very least, a clear marker for adverse neurodevelopmental outcomes, besides the adverse maternal, fetal, and neonatal outcomes identified in other studies. Healthcare providers who manage women who use cannabis during pregnancy need to be aware of these adverse outcomes.