Autism etiology

BACKGROUND: Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants...

BACKGROUND: The general factor of psychopathology, often denoted as p, captures the common variance among a broad range of psychiatric symptoms. Specific factors are co-modeled based on subsets of closely related symptoms. This paper investigated the extent to which wide-ranging genetic, personal, and environmental etiologically relevant variables are associated with p and specific psychopathology factors. METHODS: Using data from four waves (ages 11-19) of TRAILS, we modeled a bifactor model of p and four specific factors [internalizing, externalizing, ADHD, Autism Spectrum Disorder (ASD)]...

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a complex etiology. Recent evidence suggests that dopamine plays a crucial role in neural development. However, it remains unclear whether and how disrupted dopaminergic signaling during development contributes to ASD. In this study, human brain RNA-seq transcriptome analysis revealed a significant correlation between changes in dopaminergic signaling pathways and neural developmental signaling in ASD patients. In the zebrafish model, disrupted developmental dopaminergic signaling led to neural circuit abnormalities and behavior reminiscent of autism...

Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention...

Neurodevelopmental disorders are characterized by alterations in the development of the cerebral cortex, including aberrant changes in the number and function of neural cells. Although neurogenesis is one of the most studied cellular processes in these pathologies, little evidence is known about glial development. Genetic association studies have identified several genes associated with neurodevelopmental disorders. Indeed, variations in the PTPRD gene have been associated with numerous brain disorders, including autism spectrum disorder, restless leg syndrome, and schizophrenia...

Autism Spectrum Disorder (ASD) is a disturbance of neurodevelopment with a complicated pathogenesis and unidentified etiology. Many children with ASD have a history of "allergic symptoms", often in the absence of mast cell (MC)-positive tests. Activation of MCs by various stimuli may release molecules related to inflammation and neurotoxicity, contributing to the development of ASD. The aim of the present paper is to enrich the current knowledge on the relationship between MCs and ASD by discussing key molecules and immune pathways associated with MCs in the pathogenesis of autism...

Intellectual disabilities (ID) and autism spectrum disorders (ASD) have a variety of etiologies, including environmental and genetic factors. Our study reports a psychiatric clinical investigation and a molecular analysis using whole exome sequencing (WES) of two siblings with ID and ASD from a consanguineous family. Bioinformatic prediction and molecular docking analysis were also carried out. The two patients were diagnosed with profound intellectual disability, brain malformations such as cortical atrophy, acquired microcephaly, and autism level III...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090)...

Autism spectrum disorder is a neurodevelopmental condition that involves limitations in social communication and various stereotypical repetitive behaviors. Genetic and environmental factors both play a role in the etiology. Numerous genetic syndromes accompanying autism spectrum disorders have been reported. Hypoventilation, hypotonia, intellectual disability, epilepsy, eye abnormality (HIDEA) syndrome is a rare genetic condition consisting of a combination of features such as hypoventilation, hypotonia, intellectual disability, eye abnormalities, and epilepsy...

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...

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with overlapping behavioral features and genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD and ADHD separately, the degree to which ASD and ADHD are associated with common and distinct patterns of CTh changes is unclear. METHODS: We searched PubMed, Web of Science, Embase, and Science Direct from inception to 8 December 2023 and included studies of cortical thickness comparing youth (age less than 18) with ASD or ADHD with typically developing controls (TDC)...

Sleep problems are common in children with autism spectrum disorder (ASD), with 40% to 80% prevalence. Common disorders include insomnia, parasomnias, and circadian rhythm sleep-wake disorders. These problems have a multifactorial etiology and can both exacerbate and be exacerbated by core ASD symptoms. Sleep problems also impact the health and quality of life of both patients and their caregivers. All children with autism should be regularly screened for sleep problems and evaluated for co-occurring medical contributors...

Autism spectrum disorder (ASD) is clinically and etiologically heterogeneous. A causal genetic variant can be identified in approximately 20% to 25% of affected individuals with current clinical genetic testing, and all patients with an ASD diagnosis should be offered genetic etiologic evaluation. We suggest that exome sequencing with copy number variant coverage should be the first-line etiologic evaluation for ASD. Neuroimaging, neurophysiologic, metabolic, and other biochemical evaluations can provide insight into the pathophysiology of ASD but should be recommended in the appropriate clinical circumstances...

Autism spectrum disorder (ASD) is estimated to influence as many as 1% children worldwide, but its etiology is still unclear. It has been suggested that gut microbiomes play an important role in regulating abnormal behaviors associated with ASD. A de facto standard analysis on the microbiome-associated diseases has been diversity analysis, and nevertheless, existing studies on ASD-microbiome relationship have not produced a consensus. Here, we perform a comprehensive analysis of the diversity changes associated with ASD involving alpha-, beta-, and gamma-diversity metrics, based on 8 published datasets consisting of 898 ASD samples and 467 healthy controls (HC) from 16S-rRNA sequencing...

Autism is heterogeneous at many levels, including clinical symptoms and etiology. A key strategy in studying heterogeneous conditions is having large enough sample sizes to stratify into smaller groups that are more homogeneous. SPARK and Simons Searchlight are large and growing research cohorts of individuals with autism in the United States and individuals with genetically defined neurodevelopmental conditions around the world, respectively. They both provide freely available phenotypic and genotypic data with the ability to re-contact participants through the research match program...

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by deficient social communication and interaction together with restricted, stereotyped behaviors. Currently approved treatments relieve comorbidities rather than core symptoms. Since excitation/inhibition balance and synaptic plasticity are disrupted in ASD, molecules targeting excitatory synaptic transmission appear as highly promising candidates to treat this pathology. Among glutamatergic receptors, the NMDA receptor has received particular attention through the last decade to develop novel allosteric modulators...

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...

The multifactorial etiology of autism spectrum disorder (ASD) suggests that its study would benefit greatly from multimodal approaches that combine data from widely varying platforms, e.g., neuroimaging, genetics, and clinical characterization. Prior neuroimaging-genetic analyses often apply naive feature concatenation approaches in data-driven work or use the findings from one modality to guide posthoc analysis of another, missing the opportunity to analyze the paired multimodal data in a truly unified approach...

BACKGROUND: The concept of schizotypal personality disorder (SPD) emerged from observations of personality characteristics common in relatives of schizophrenic patients. While often studied in family designs, few studies and none with genetic measures, have examined SPD in epidemiological samples. METHODS: We studied individuals born in Sweden 1940-2000 with an ICD-10 diagnosis of SPD with no prior schizophrenia (SZ) diagnosis ( n = 2292). Demographic features, patterns of comorbidity, and Family Genetic Risk Scores (FGRS) were assessed from multiple Swedish registries...

The dopamine D4 receptor 7-repeat allele (D4.7 R) has been linked with psychiatric disorders such as attention-deficit-hyperactivity disorder, autism, and schizophrenia. However, the highly diverse study populations and often contradictory findings make it difficult to draw reliable conclusions. The D4.7 R has the potential to explain individual differences in behavior. However, there is still a great deal of ambiguity surrounding whether it is causally connected to the etiology of psychiatric disorders. Therefore, humanized D4...