Etiology Of Autism Spectrum Disorder Research Articles

Prenatal & Perinatal Risk Factors of Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is lifelong neurodevelopmental disorder characterized by impairments in social function, communication, and certain behaviors. The etiology of ASD is unclear & it is believed to be multi-factorial, among those several prenatal & perinatal factors are found to be significant. So, the necessity of this study is to detect the presence of known risk factors of ASD which in turn may help in the early diagnosis and intervention for better long-term outcomes. Objective: To find out prenatal and perinatal risk factors of ASD. Method: A case control study was conducted with 112 cases of ASD and 201 controls of 2-6 years of age. The study was carried out in Center for Neurodevelopment and Autism in Children (CNAC), in the department of Paediatrics, Bangabandhu Sheikh Mujib Medical University and Autism Welfare Foundation (AWF). ASD was diagnosed by DSM-IV TR criteria. Mothers were interviewed and data were collected by semistructured questionnaires. Results: Total 5 risk factors were identified as the risk factors of ASD. They were: advanced paternal age (OR=2.84) and maternal age (OR=1.87); male baby (OR=2.01); environmental stress during pregnancy (OR=1.61) and preterm delivery (OR=1.80). Conclusions: It is concluded that advanced paternal age, maternal age, male baby, environmental stress during pregnancy and preterm delivery are associated with increased risk of ASD. BANGLADESH J CHILD HEALTH 2022; VOL 46 (3) : 115-121

Microglial Dysfunction in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with onset in childhood. The molecular mechanisms underlying ASD have not yet been elucidated completely. Evidence has emerged to support a link between microglial dysfunction and the etiology of ASD. This review summarizes current research on microglial dysfunction in neuroinflammation and synaptic pruning, which are associated with altered transcriptomes and autophagy in ASD. Dysbiosis of gut microbiota in ASD and its correlation with microglial dysfunction are also addressed.

Management of Autism Spectrum Disorder Through Ayurvedic Intervention and Diet Modifications

Autism spectrum disorder includes a group of neurodevelopmental disorders, which disrupts normal functioning of the brain and impairs communication, social interaction, emotional balance with the presence of repetitive stereotypic mannerisms. Underlying etiology of autism spectrum disorder is still unknown. Studies on genetic causes, immune system dysregulation, inflammation, exposure to environmental toxicants, defective gut microbiome are still continuing. In ayurveda, most psycho social abnormalities are included in the category of Unmada. Along with other etiological factors, impaired digestive and metabolic functions are postulated as the root cause of Unmada. And in accord with the gut brain axis, systemic accumulation of metabolic wastes also disrupts the functional integrity of the brain. The present study describes the case of a child with ASD with hyperactivity, who has been clinically diagnosed and treated with Ayurvedic medications, Sneha sweda therapies and diet modifications, which helps in maintaining the healthy functioning of the brain. Within 3 months of intervention, the child became symptomatically better. Case study briefs Ayurvedic concepts and Ayurvedic treatment protocols regarding ASD.

Environmental Risk Factors in Autism Spectrum Disorder: A Narrative Review.

Existing evidence indicates that environmental factors might contribute up to 50% of the variance in autism spectrum disorder (ASD) risk. This structured narrative review offers a comprehensive synthesis of current knowledge on environmental risk factors in ASD, including evaluation of conflicting evidence, exploration of underlying mechanisms, and suggestions for future research directions. Analysis of diverse epidemiological investigations indicates that certain environmental factors, including advanced parental age, preterm birth, delivery complications, and exposure to toxic metals, drugs, air pollutants, and endocrine-disrupting chemicals, are linked to an increased ASD risk through various mechanisms such as oxidative stress, inflammation, hypoxia, and its consequences, changes in neurotransmitters, disruption of signaling pathways and some others. On the other hand, pregnancy-related factors such as maternal diabetes, maternal obesity, and caesarian section show a weaker association with ASD risk. At the same time, other environmental factors, such as vaccination, maternal smoking, or alcohol consumption, are not linked to the risk of ASD. Regarding nutritional elements data are inconclusive. These findings highlight the significance of environmental factors in ASD etiology and emphasize that more focused research is needed to target the risk factors of ASD. Environmental interventions targeting modifiable risk factors might offer promising avenues for ASD prevention and treatment.

Classification of Autism Spectrum Disorder using Resting State-Functional Magnetic Resonance Imaging and Artificial Neural Network

Autism Spectrum Disorder (ASD) represents a growing challenge in public health, characterized by irreversible neurodevelopmental abnormalities. Despite a rising prevalence, the underlying aetiology and neural substrates of ASD remain incompletely understood. Resting state-functional Magnetic Resonance Imaging (rs-fMRI) has emerged as a valuable non-invasive tool for probing the organization and cognitive functions of the brain by capturing hemodynamic changes. This study explores the relationship between Functional Connectivity (FC) alterations, measured by rs-fMRI, and the manifestation of ASD-related brain disorders. In this paper, we propose a hybrid approach employing an InfoMax Independent Component Analysis (ICA) algorithm and Artificial Neural Network to distinguish between the ASD subjects and Healthy Controls (HCs). Initially, rs-fMRI datasets are preprocessed using Statistical Parametric Mapping (SPM). Further, these datasets are processed using InfoMax ICA to extract the distinct features such as fractional Amplitude of Low-Frequency Fluctuations (fALFF) and Dynamic Range and visualize the FC alterations by region mapping. In addition to this, the number of activated voxels for each brain regions are estimated to observe the neural abnormalities. Finally, the extracted features are fed as input to train, test and validate the ANN classifier. The efficacy of the proposed network is evaluated using the Autism Brain Imaging Data Exchange (ABIDE) dataset and an accuracy of 75.3 percentage is achieved.

Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish

The etiology of autism spectrum disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed to during embryogenesis. Conversely, in animal models, enriched environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe deficits in social communication and interaction, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid or acetaminophen, or ingestion of propionic acid, can increase the risk of ASD. Recently, epigenetic influences on ASD have come to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here, we specifically focus on the molecular influences of the abovementioned chemicals on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. We conclude that a better understanding of these phenomena can lead to more effective interventions in ASD.

Innate Immune Dysfunction and Neuroinflammation in Autism Spectrum Disorder (ASD).

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by communication and social behavior deficits. The presence of restricted and repetitive behaviors often accompanies these deficits, and these characteristics can range from mild to severe. The past several decades have seen a significant rise in the prevalence of ASD. The etiology of ASD remains unknown; however, genetic and environmental risk factors play a role. Multiple hypotheses converge to suggest that neuroinflammation, or at least the interaction between immune and neural systems, may be involved in the etiology of some ASD cases or groups. Repeated evidence of innate immune dysfunction has been seen in ASD, often associated with worsening behaviors. This evidence includes data from circulating myeloid cells and brain resident macrophages/microglia in both human and animal models. This comprehensive review presents recent findings of innate immune dysfunction in ASD, including aberrant innate cellular function, evidence of neuroinflammation, and microglia activation. Appeared originally in Brain Behav Immun 2023; 108:245-254.

The genetic landscape of autism spectrum disorder in the Middle Eastern population.

Introduction: Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk. Methods: We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify de novo or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents). Results: Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel de novo variants in new candidate genes for ASD (DTX4, ARMC6, and B3GNT3). Also, we have identified 15 de novo variants in genes that were previously implicated in ASD or related neurodevelopmental disorders (PHF21A, WASF1, TCF20, DEAF1, MED13, CREBBP, KDM6B, SMURF1, ADNP, CACNA1G, MYT1L, KIF13B, GRIA2, CHM, and KCNK9). Additionally, we defined eight novel recessive variants (RYR2, DNAH3, TSPYL2, UPF3B KDM5C, LYST, and WNK3), four of which were X-linked. Conclusion: Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population.

The Use of CGH Arrays for Identifying Copy Number Variations in Children with Autism Spectrum Disorder.

Autism spectrum disorders (ASDs) encompass a broad group of neurodevelopmental disorders with varied clinical symptoms, all being characterized by deficits in social communication and repetitive behavior. Although the etiology of ASD is heterogeneous, with many genes involved, a crucial role is believed to be played by copy number variants (CNVs). The present study examines the role of copy number variation in the development of isolated ASD, or ASD with additional clinical features, among a group of 180 patients ranging in age from two years and four months to 17 years and nine months. Samples were taken and subjected to array-based comparative genomic hybridization (aCGH), the gold standard in detecting gains or losses in the genome, using a 4 × 180 CytoSure Autism Research Array, with a resolution of around 75 kb. The results indicated the presence of nine pathogenic and six likely pathogenic imbalances, and 20 variants of uncertain significance (VUSs) among the group. Relevant variants were more prevalent in patients with ASD and additional clinical features. Twelve of the detected variants, four of which were probably pathogenic, would not have been identified using the routine 8 × 60 k microarray. These results confirm the value of microarrays in ASD diagnostics and highlight the need for dedicated tools.

NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways

BackgroundEpigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic...

The complex etiology of autism spectrum disorder due to missense mutations of CHD8.

CHD8 is an ATP-dependent chromatin-remodeling factor encoded by the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Although many studies have examined the consequences of CHD8 haploinsufficiency in cells and mice, few have focused on missense mutations, the most common type of CHD8 alteration in ASD patients. We here characterized CHD8 missense mutations in ASD patients according to six prediction scores and experimentally examined the effects of such mutations on the biochemical activities of CHD8, neural differentiation of embryonic stem cells, and mouse behavior. Only mutations with high prediction scores gave rise to ASD-like phenotypes in mice, suggesting that not all CHD8 missense mutations detected in ASD patients are directly responsible for the development of ASD. Furthermore, we found that mutations with high scores cause ASD by mechanisms either dependent on or independent of loss of chromatin-remodeling function. Our results thus provide insight into the molecular underpinnings of ASD pathogenesis caused by missense mutations of CHD8.

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy.

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal-fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.

Correlation analysis of maternal condition during pregnancy with head circumference and autism spectrum disorder: A propensity score-matched study.

To determine whether health status during pregnancy is associated with autism spectrum disorder (ASD) and abnormal head circumference (HC) in the offspring. This study included 41 Han children with ASD who visited the Children's Health Clinic of the Second Hospital of Shandong University between March 2018 and February 2019, and 264 Han children with typical development (TD) who visited the clinic during the same period. Physical measurements were performed on the children. The questionnaire obtained information on maternal risk factors that may be related to the increased risk of ASD and folic acid (FA) supplementation. We designed an observational case-control study using propensity score matching and multivariate logistic regression analysis. The incidence of macrocephaly in the ASD group was 22.0%, significantly higher than that in the TD group (1.8%). The incidence of microcephaly in the ASD group was 17.1% (n = 7), significantly higher than that in the TD group (1.8%). The differences between the comparisons were statistically significant. Maternal FA supplementation during pregnancy was significantly associated with ASD (P < .05), with an odds ratio (95% confidence interval of 3.69 (1.76, 7.76)). Also was associated with macrocephaly (P < .05), odds ratio (95% confidence interval) were 8.13 (1.63, 40.61) and 4.16 (1.18, 14.60), respectively. The incidence of abnormal HC was higher in the ASD group than that in the TD group. Maternal FA supplementation during pregnancy may be negatively associated with the occurrence of ASD and abnormal HC in the offspring. Further examination of the role of maternal health status in the etiology of ASD is recommended.

Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism.

Background: Autism spectrum disorders (ASDs) encompass a broad range of phenotypes characterized by diverse neurological alterations. Genomic studies have revealed considerable overlap between the molecular mechanisms implicated in the etiology of ASD and genes involved in the pharmacokinetic (PK) and pharmacodynamic (PD) pathways of antipsychotic drugs employed in ASD management. Given the conflicting data originating from candidate PK or PD gene association studies in diverse ethnogeographic ASD populations, dosage individualization based on "actionable" pharmacogenetic (PGx) markers has limited application in clinical practice. Additionally, off-label use of different antipsychotics is an ongoing practice, which is justified given the shortage of approved cures, despite the lack of satisfactory evidence for its safety according to precision medicine. This exploratory study aimed to identify PGx markers predictive of risperidone (RIS) exposure in autistic Saudi children. Methods: This prospective cohort study enrolled 89 Saudi children with ASD treated with RIS-based antipsychotic therapy. Plasma levels of RIS and 9-OH-RIS were measured using a liquid chromatography-tandem mass spectrometry system. To enable focused exploratory testing, genotyping was performed with the Axiom PharmacoFocus Array, which included a collection of probe sets targeting PK/PD genes. A total of 720 PGx markers were included in the association analysis. Results: A total of 27 PGx variants were found to have a prominent impact on various RIS PK parameters; most were not located within the genes involved in the classical RIS PK pathway. Specifically, 8 markers in 7 genes were identified as the PGx markers with the strongest impact on RIS levels (p < 0.01). Four PGx variants in 3 genes were strongly associated with 9-OH-RIS levels, while 5 markers in 5 different genes explained the interindividual variability in the total active moiety. Notably, 6 CYP2D6 variants exhibited strong linkage disequilibrium; however, they significantly influenced only the metabolic ratio and had no considerable effects on the individual estimates of RIS, 9-OH-RIS, or the total active moiety. After correction for multiple testing, rs78998153 in UGT2B17 (which is highly expressed in the brain) remained the most significant PGx marker positively adjusting the metabolic ratio. For the first time, certain human leukocyte antigen (HLA) markers were found to enhance various RIS exposure parameters, which reinforces the gut-brain axis theory of ASD etiology and its suggested inflammatory impacts on drug bioavailability through modulation of the brain, gastrointestinal tract and/or hepatic expression of metabolizing enzymes and transporters. Conclusion: Our hypothesis-generating approach identified a broad spectrum of PGx markers that interactively influence RIS exposure in ASD children, which indicated the need for further validation in population PK modeling studies to define polygenic scores for antipsychotic efficacy and safety, which could facilitate personalized therapeutic decision-making in this complex neurodevelopmental condition.

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models.

Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development.

Autism spectrum disorder in ICD-11-a critical reflection of its possible impact on clinical practice and research.

This perspective article compares and contrasts the conceptualization of Autism Spectrum Disorder (ASD) in ICD-11 and DSM-5. By guiding the user through the ICD-11 text, it is argued that, in contrast to DSM-5, ICD-11 allows a high variety in symptom combinations, which results in an operationalization of ASD that is in favor of an extreme diverse picture, yet possibly at the expense of precision, including unforeseeable effects on clinical practice, care, and research. The clinical utility is questionable as this conceptualization can hardly be differentiated from other mental disorders and autism-like traits. It moves away from an observable, behavioral, and neurodevelopmental disorder to a disorder of inner experience that can hardly be measured objectively. It contains many vague and subjective concepts that lead to non-falsifiable diagnoses. This bears a large danger of false positive diagnoses, of further increased prevalence rates, limitations of access to ASD-specific services and of increasing the non-specificity of treatments. For research, the hypothesis is that the specificity of ASD will be reduced and this will additional increase the already high heterogeneity with the effect that replication of studies will be hampered. This could limit our understanding of etiology and biological pathways of ASD and bears the risk that precision medicine, i.e., a targeted approach for individual treatment strategies based on precise diagnostic markers, is more far from becoming reality. Thus, a more precise, quantitative description and more objective measurement of symptoms are suggested that define the clinical ASD phenotype. Identification of core ASD subtypes/endophenotypes and a precise description of symptoms is the necessary next step to advance diagnostic classification systems. Therefore, employing a more finely grained, objective, clinical symptom characterization which is more relatable to neurobehavioral concepts is of central significance.

Des-Arg(9) bradykinin as a causal metabolite for autism spectrum disorder.

Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder (ASD). However, the etiology of ASD is not completely understood. The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD. To estimate and interpret the causal relationship between ASD and metabolite profile, taking into consideration both genetic and environmental influences. A two-sample Mendelian randomization (MR) analysis was conducted using summarized data from large-scale genome-wide association studies (GWAS) including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls. Metabolites in plasma were set as exposures with ASD as the main outcome. The causal relationships were estimated using the inverse variant weight (IVW) algorithm. We also performed leave-one-out sensitivity tests to validate the robustness of the results. Based on the drafted metabolites, enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome, SwissTargetPrediction, STRING, and Metascape. Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD (β = 0.262, SE = 0.064, PIVW = 4.64 × 10-5). The association was robust, with no significant heterogeneity among instrument variables (PMR Egger = 0.663, PIVW = 0.906) and no evidence of pleiotropy (P = 0.949). Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9) bradykinin and ASD. Through the application of MR, this study provides practical insights into the potential causal association between plasma metabolites and ASD. These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.

Comparison of HMGB1, RAGE, TLR4, and NF-κB levels in children and adolescents diagnosed with autism spectrum disorder with healthy controls

Introduction The objective of our study is to clarify the involvement of the HMGB1/RAGE/TLR4/NF-kB axis, a crucial component in inflammation, in the etiopathogenesis of autism spectrum disorder (ASD). Method We analyzed the levels of HMGB1, RAGE, TLR4, and NF-kB in serum from 80 children (40 with ASD and 40 controls). All participants’ sociodemographic characteristics were recorded. In order to determine the severity of the disorder, the Aberrant Behavior Checklist, Childhood Autism Rating Scale, and Autism Behavior Checklist were administered to the ASD group. Result While the soluble TLR4 level was significantly higher in the ASD group (p < 0.001), other parameters examined did not show significant differences between groups. Furthermore, soluble TLR4 serum level was positively correlated with Problem Behavior Checklist hyperactivity subscale scores (p = 0.031), and RAGE serum level was negatively correlated with ABC Stereotype score (p = 0.001). Discussion It was thought that serum TLR4 levels may be important in the etiology of ASD. TLR4 levels are linked to symptoms like hyperactivity in autism, which suggests that this parameter could be used as a clinical guide. Further research is required to substantiate our discoveries and to clarify the involvement of HMGB1, RAGE, TLR4, and NF-kB in the etiopathogenesis of ASD.