Template to Perpetrate: An Update on Violence in Autism Spectrum Disorder

Assisted reproductive technology and risk for autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Emerging evidence suggests a link between immune dysregulation and ASD. This study investigates alterations in monocyte subpopulations and cytokine production in children with ASD and their potential associations with ASD risk and severity. Initially, the immune status of peripheral blood mononuclear cells was assessed in cohort-I of 96 typically developing (TD) children and 92 children diagnosed with ASD using flow cytometry. Subsequently, the secretion of cytokines IL-6 and IL-10 by monocytes was evaluated following stimulation with a leukocyte activation mixture and intracellular protein staining technique in cohort-II. Children with ASD exhibited significantly higher levels of total monocytes, classical monocytes (CD14hi/CD16-), and non-classical monocytes (CD14low/CD16+) compared to TD children (p<0.001). Elevated levels of classical monocytes (β: 0.395; 95%CI: 0.260-0.530; p<0.001) and non-classical monocytes (β: 0.629; 95%CI: 0.516-0.742; p<0.001) were significantly associated with ASD after adjusting for age, sex and body mass index. Furthermore, increased production of IL-6 by monocytes was observed in children with ASD (p=0.001). Logistic regression analysis revealed that classical monocytes (OR: 1.104; 95%CI: 1.062-1.147; p<0.001), non-classical monocytes (OR: 2.913; 95%CI: 2.130-3.986; p<0.001) and IL-6 production by monocytes (OR: 1.306; 95%CI: 1.096-1.557; p=0.003) are risk factors for ASD. Spearman correlation analysis revealed a negative correlation between classical monocyte levels and adaptive behavior developmental quotient (DQ) (r=-0.377; p=0.001), fine motor DQ (r=-0.329; p=0.003) and personal-social DQ (r=-0.247; p=0.029) in children with ASD. Elevated classical and non-classical monocytes are potential risk factors for ASD and may influence neurodevelopmental outcomes. Further research is needed to elucidate the precise mechanisms and therapeutic implications.

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.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Early identification of high-risk infants is crucial for intervention and long-term outcomes. This study explored the association between early neurological development from 12 to 15 months and the related risk factors for ASD, with a primary focus on M-CHAT status at 24 months as the screening outcome, and the impact of family history, prematurity, and sleep disorders. We conducted a retrospective analysis of 50 children aged 24 months who tested positive on the Modified Checklist for Autism in Toddlers (M-CHAT) and 50 matched controls with negative results. Neurodevelopmental status was assessed using the Gesell Developmental Diagnosis Scale (GDDS), the Peabody Developmental Motor Scales, Second Edition (PDMS-2), and the Sensory Integration Schedule (SIS). Statistical analyses, including logistic regression, were used to evaluate associations among baseline characteristics, neurodevelopmental scores, and ASD risk factors. A total of 100 infants were included, with 50 classified as high risk and 50 as low risk. High-risk infants had significantly higher rates of family history of ASD, prematurity, and sleep disorders. They showed impairments across several PDMS-2 subscales, including stationary, locomotion, and grasping, as well as GDDS subscales such as adaptability and language. Logistic regression analysis revealed that neurodevelopmental impairments were significantly associated with M-CHAT positivity at 24 months. Early neurodevelopmental impairments in infants aged 12 to 15 months may serve as important indicators of ASD risk. Identifying these factors may facilitate timely intervention and improve outcomes for high-risk children.

Background: Indonesia has experienced an increased number of children with autism spectrum disorder (ASD). One of the challenges that Indonesia currently faces is how to reduce the perinatal and risk factors related with the incidence of autism. This study aimed to identify the perinatal and risk factors contributing to ASD. Method: This research was a case control study involving 52 children with ASD in the case group and 201 normal children in the control group in Banyumas district, Province of Central Java, Indonesia. Data collection used independently completed questionnaires, concerning perinatal factors such as maternal age at birthing, gestational age, labor method, fetus presentation in labor, and history of complications during labor. Results: Stepwise logistic regression analysis indicated a higher risk of preterm gestational age among children in the ASD group with p=0.019 and OR:5.883. Abnormal delivery method such as caesarean delivery or vacuum extraction also had association with the ASD group (p=0.001; OR=0.303). Abnormal fetus presentation during labor increased the risk of ASD (p=0.004; OR:6.908). Mother with complication during labor such as difficult labor, preeclampsia, and fetal distress correlated with ASD (p=0,.021; OR:2.101). Multivariate analysis also showed complications during labor became a risk factor for ASD (OR: 2.142 (1.904-4.196). There was no correlation between maternal age below 20 years (p=0.332; OR=1.871) or 31-40 years (p=0.115; OR=2.868) with ASD. Conclusion: Labor method, fetus presentation, and complication during labor were significantly related with ASD.

Psychological distress, such as stress, depression or anxiety, is a prevalent mental health concern during pregnancy. However, data on the association between prenatal maternal psychological distress and the risk of autism or autism spectrum disorders (ASD) in their offspring have not been synthesized systematically. We performed a meta-analysis to explore this issue and provide evidence regarding maternal mental health screening and ASD prevention. Six electronic databases were systematically searched up to June 2025. English-language full-text observational studies were included, with no geographic or race restrictions. Studies that quantitatively assessed the association between maternal psychological distress during pregnancy and the risk of ASD in offspring were eligible for inclusion. Pooled odds ratios (ORs) were calculated. Heterogeneity, publication bias, and sensitivity analyses were assessed. Among 484 full-text records screened, 22 studies were eligible. Data analysis demonstrated that offspring of mothers with prenatal psychological distress have a 72% higher likelihood of being diagnosed with ASD or autism after the age of two (OR = 1.72, 95% CI 1.50-1.97, p < 0.01) compared to those of mothers without distress. This association was observed across different study designs and ASD diagnostic ascertainment methods, although effect estimates varied. Substantial between-study heterogeneity was observed (I 2 = 87.90%), largely attributable to differences in study design, ASD ascertainment and distress assessment rather than psychological distress subtype. In this meta-analysis, prenatal maternal psychological distress was associated with an increased likelihood of an ASD diagnosis in offspring. Across the included studies, effect estimates were generally similar for stress, depression, and anxiety, despite substantial heterogeneity in study design and exposure assessment. This consistency suggests that elevated ASD risk is not confined to a single diagnostic category of maternal distress. At the same time, the findings should be interpreted considering the variability in how psychological distress was measured and controlled for across studies. Taken together, the results indicate that maternal psychological distress during pregnancy warrants attention in epidemiological research and routine antenatal care, without implying that specific psychiatric subtypes can be clearly distinguished in terms of offspring ASD risk. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251119825, PROSPERO: CRD420251119825.

Previous studies suggested that lower vitamin D might be a risk factor for autism spectrum disorders (ASDs). The aim of this study was to estimate the prevalence of ASDs in 3-year-old Chinese children and to examine the association between neonatal vitamin D status and risk of ASDs. We conducted a study of live births who had taken part in expanded newborn screening (NBS), with outpatient follow-up when the children 3-year old. The children were confirmed for ASDs in outpatient by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was defined by the intelligence quotient (IQ < 80) for all the participants. The study design included a 1:4 case to control design. The concentration of 25-hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from neonatal dried blood samples. A total of 310 children were diagnosed as having ASDs; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level was significantly lower in children with ASD as compared to controls (p < 0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile: 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5; 95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1 to 3.3; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk relationship was more prominent when the data were assessed in deciles. This model predicted the lowest relative risk of ID in the 72rd percentile (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was significantly associated with the risk of ASDs and intellectual disability. The nature of those relationships was nonlinear. © 2017 American Society for Bone and Mineral Research.

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA-). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother–child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.

Background and AimExposure to stressful life events during pregnancy has been suggested as a potential risk factor for offspring Autism Spectrum Disorders (ASD), but the literature is limited and inconsistent. We tested the hypothesis that maternal exposure to stressful life events would be associated with increased risks of offspring ASD, and that these risks would be highest for exposures during the prenatal period.Methods and ResultsWe used prospectively collected data from two large population based studies in Sweden and England. In the Swedish study of 4429 ASD cases and 43277 controls, our exposure comprised the occurrence of any severe life event before and during pregnancy and the child's early life. In the English study (maximum n = 11554, ASD n = 72), we studied the risk of offspring ASD in relation to a combined maternal exposure to multiple (up to 42) common and rare life events, as well as their perceived impact upon the mother during pregnancy and early life. In crude and adjusted regression analyses in both studies, we found no evidence of an association between prenatal life events, or their number and perceived impact and the risk of offspring ASD. Sub-group analysis of ASD with and without intellectual disability in the Swedish study yielded similar results.ConclusionWe found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

BackgroundSchizophrenia (SCZ) is a clinically and genetically heterogeneous disorder that shares genetic factors with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). A genome-wide association study (GWAS) differentiating ADHD from ASD was performed recently. Although genetic correlations of regional cortical structures with the risk of SCZ, ASD, and ADHD have been identified, no study has yet investigated the genetic correlations between the genetic factor differentiating ADHD from ASD and brain cortical structures or whether this genetic factor influences cognitive functions and brain cortical structures in patients with SCZ.Aims & ObjectivesGiven the clinical and genetic heterogeneity of SCZ and its significant overlap with ASD and ADHD, our study focuses specifically on SCZ to better understand the distinct genetic contributions to cognitive impairments and cortical abnormalities within this population. By isolating SCZ as the primary condition, we aim to elucidate the unique and shared genetic underpinnings that differentiate it from other neurodevelopmental disorders.The significance of this study lies in its potential to unravel the specific genetic influences on cognitive impairments and cortical abnormalities in SCZ. By exploring the polygenic risk scores (PRSs) differentiating ADHD from ASD, we aim to contribute to the understanding of the genetic architecture that impacts cognitive functions and brain structures in SCZ. This could lead to more precise diagnostic tools and personalized treatment strategies, ultimately improving outcomes for individuals with SCZ.MethodBased on the GWAS data (9,315 ASD and 11,964 ADHD patients), PRSs differentiating ADHD from ASD (indicating a greater risk of ADHD and a lower risk of ASD) were calculated for SCZ patients (n=168). Cognitive performance, including verbal comprehension (VC), perceptual organization (PO), working memory (WM), and processing speed (PS), was assessed using the WAIS-III (n=145). The surface areas and cortical thicknesses of 34 bilateral brain regions were extracted using FreeSurfer (n=126). We examined the associations of these PRSs with cognitive performance and cortical structures in SCZ patients.ResultsAmong the four cognitive domains, a higher PRS, indicating a greater risk of ADHD, was associated with impaired WM in SCZ patients (beta=-0.21, p=0.012). A lower PRS, indicating a greater risk of ASD, was associated with decreased surface areas of the left medial orbitofrontal (beta=0.21, p=8.29×10-4), left entorhinal (beta=0.21, p=0.025), left postcentral (beta=0.18, p=7.52×10-3), right fusiform (beta = 0.17, p = 6.64×10-3), and left fusiform cortices (beta=0.17, p=7.77×10-3) in SCZ patients. A higher PRS, indicating a greater risk of ADHD, was associated with decreased cortical thickness in the bilateral transverse temporal regions (left, beta=-0.17, p=0.039; right, beta=-0.17, p=0.045).Discussion & ConclusionsOur study revealed a relationship between genetic factors that differentiate ADHD patients from ASD patients and both cortical structure and cognitive performance in SCZ patients. These findings suggest that the heterogeneity of SCZ might be partly derived from genetic factors related to neurodevelopmental and psychiatric disorders other than SCZ.

Advances in Our Understanding of Genetic Risk Factors for Autism Spectrum Disorders

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Therefore, this study investigated whether preterm birth is a risk factor for subsequent epilepsy, ASD, and ADHD in children with FS. We retrospectively collected data for children aged < 5 years with FS from 1 January 2005, to 31 December 2013. We divided these children into two groups—the premature birth group and the full-term group—and compared their incidence rates of epilepsy, ASD and ADHD. The data of 426 patients with history of febrile convulsion were retrospectively collected. The premature birth group (FS+/preterm+) had 108 patients and the full-term group (FS+/preterm−) had 318 patients. The overall epilepsy risk in the FS+/preterm+ group was higher than in the FS+/preterm− group (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.14–5.58; p = 0.02). The overall risk of ADHD in the FS+/preterm+ group was higher than that in the FS+/preterm− group (OR, 6.41; 95% CI, 3.39–12.09; p = 0.0001). In addition, children with FS+/preterm+ had 16.9 times (95% CI, 4.79–59.7; p = 0.0001) higher odds of having ASD compared with those with FS+/preterm−. Preterm birth may be a risk factor for subsequent epilepsy, ASD and ADHD in children with FS.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication and by the presence of restrictive, repetitive behavior. Attention deficit hyperactivity disorder (ADHD) is another common lifelong neurodevelopmental disorder characterized by three major presentations: predominantly hyperactive/impulsive, predominantly inattentive, and combined. Although ASD and ADHD are different clinical diagnoses, they share various common characteristics, including male dominance, early childhood onset, links to prenatal and perinatal factors, common comorbidity for each other, and, often, persistence into adulthood. They also have both unique and shared risk factors, which originate in early life and have lifelong implications on the affected individuals and families and society. While genetic factors contribute to ASD and ADHD risk, the environmental contribution to ASD and ADHD has been recognized as having potentially equal importance, which raises the hope for early prevention and intervention. Maternal folate levels, maternal metabolic syndrome, and metabolic biomarkers have been associated with the risk of childhood ASD; while maternal high-density lipoprotein, maternal psychosocial stress, and in utero exposure to opioids have been associated with the risk of childhood ADHD. As for shared factors, male sex, preterm birth, placental pathology, and early life exposure to acetaminophen have been associated with both ASD and ADHD. The high rate of comorbidity of ASD and ADHD and their many shared early life risk factors suggest that early identification and intervention of common early life risk factors may be cost-effective to lower the risk of both conditions. Efforts to improve maternal preconception, prenatal, and perinatal health will not only help reduce adverse reproductive and birth outcomes but will also help mitigate the risk of ASD and ADHD associated with those adverse early life events.

Given the ongoing rise in prevalence of autism spectrum disorder (ASD) and the challenges in developing and administering interventions to significantly alleviate ASD symptoms, there is an urgent need to identify modifiable risk factors for ASD. The goal of this review is to systematically evaluate the current evidence for an association between conditions related to maternal metabolic syndrome and risk for ASD in offspring focusing on methodically rigorous studies. In recent years, multiple studies explored the association between various conditions related to maternal metabolic syndrome (obesity, hypertension, or diabetes prior to, or with onset during pregnancy) and ASD risk in the offspring. Examining large, sufficiently powered, population-based epidemiological studies that explored the association between maternal metabolic syndrome and ASD, we found consistent evidence for an association between maternal preeclampsia and risk for ASD. Other conditions that are part of maternal metabolic syndrome, including maternal obesity, gestational weight gain, diabetes and gestational diabetes, should be studied further with careful attention paid to potential synergistic effects between different metabolic conditions. These findings highlight the need for rigorous, large, population-based epidemiological studies of potentially modifiable ASD risk factors that could inform public health interventions.

Autism spectrum disorders (ASD) are syndromes that are predominantly defined by behavioral features such as impaired social interactions, restricted verbal and nonverbal communication, and repetitive or stereotyped behavior. In the past few decades, the reported prevalence of ASD has increased dramatically. This growth can be partially explained by an increased level of awareness of the problem among professionals and better diagnostic methods. Nevertheless, underpinning causes of ASD have not yet been detailed and explained. It is suggested that rather than having asingle causative factor, ASD pathogenesis is influenced by environmental or genetic factors, or a combination of both. The aims of this review are to describe the environmental risk factors associated with ASD so as to provide areference basis for current and future clinical and experimental work. On the basis of a PubMed search, we review the existing knowledge on environmental factors associated with ASD. Aseries of environmental factors have been repeatedly reported as risk factors for ASD in existing studies. Air pollution, organic toxicants, seasonal factors, psychological stress, migration, birth order, and nutrition may have a close relationship with the incidence of ASD.