-
International Journal of Molecular... Apr 2024Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of... (Review)
Review
Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.
Topics: Humans; Autism Spectrum Disorder; Neuroimaging; Brain; Electroencephalography; Genetic Predisposition to Disease
PubMed: 38732157
DOI: 10.3390/ijms25094938 -
Journal of Autism and Developmental... Dec 2023Theories about autism spectrum disorder (ASD) have addressed cognitive deficits however few have examined how comorbid diagnoses, including sleep disturbance, anxiety...
Theories about autism spectrum disorder (ASD) have addressed cognitive deficits however few have examined how comorbid diagnoses, including sleep disturbance, anxiety and depression contribute to the underlying deficits. We investigated potential mediations of common ASD comorbidities in the relationship between sub-clinical autism traits and cognitive performance using an international community sample. Cognitive tasks assessed working memory [executive functioning (EF) theory], mental state attribution [theory of mind (ToM)], and global/local visual processing [weak central coherence (WCC) theory]. Structural equation modelling (SEM) demonstrated sleep disturbance and anxiety mediated the relationship of autism traits on measures of EF, but not WCC and ToM. This suggests that treating the symptoms of sleep disturbance and anxiety may lead to improvements in working memory.
Topics: Humans; Autism Spectrum Disorder; Autistic Disorder; Depression; Executive Function; Anxiety; Theory of Mind; Cognition; Sleep
PubMed: 36138298
DOI: 10.1007/s10803-022-05742-5 -
Molecular Autism Jul 2023Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person's perception and socialization with others. Here, we examined...
BACKGROUND
Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person's perception and socialization with others. Here, we examined variability in the brain morphology in ASD children and adolescent individuals at the level of brain cortical structural profiles and the level of each brain regional measure.
METHODS
We selected brain structural MRI data in 600 ASDs and 729 normal controls (NCs) from Autism Brain Imaging Data Exchange (ABIDE). The personalized estimate of similarity between gray matter volume (GMV) profiles of an individual to that of others in the same group was assessed by using the person-based similarity index (PBSI). Regional contributions to PBSI score were utilized for brain age gap estimation (BrainAGE) prediction model establishment, including support vector regression (SVR), relevance vector regression (RVR), and Gaussian process regression (GPR). The association between BrainAGE prediction in ASD and clinical performance was investigated. We further explored the related inter-regional profiles of gene expression from the Allen Human Brain Atlas with variability differences in the brain morphology between groups.
RESULTS
The PBSI score of GMV was negatively related to age regardless of the sample group, and the PBSI score was significantly lower in ASDs than in NCs. The regional contributions to the PBSI score of 126 brain regions in ASDs showed significant differences compared to NCs. RVR model achieved the best performance for predicting brain age. Higher inter-individual brain morphology variability was related to increased brain age, specific to communication symptoms. A total of 430 genes belonging to various pathways were identified as associated with brain cortical morphometric variation. The pathways, including short-term memory, regulation of system process, and regulation of nervous system process, were dominated mainly by gene sets for manno midbrain neurotypes.
LIMITATIONS
There is a sample mismatch between the gene expression data and brain imaging data from ABIDE. A larger sample size can contribute to the model training of BrainAGE and the validation of the results.
CONCLUSIONS
ASD has personalized heterogeneity brain morphology. The brain age gap estimation and transcription-neuroimaging associations derived from this trait are replenished in an additional direction to boost the understanding of the ASD brain.
Topics: Child; Adolescent; Humans; Autism Spectrum Disorder; Neurobiology; Brain; Gray Matter; Magnetic Resonance Imaging
PubMed: 37507798
DOI: 10.1186/s13229-023-00558-1 -
Journal of Genetics and Genomics = Yi... Mar 2024Autistic spectrum disorder (ASD) is a male-biased, heterogeneous neurodevelopmental disorder that affects approximately 1%-2% of the population. Prenatal exposure to...
Autistic spectrum disorder (ASD) is a male-biased, heterogeneous neurodevelopmental disorder that affects approximately 1%-2% of the population. Prenatal exposure to valproic acid (VPA) is a recognized risk factor for ASD, but the cellular and molecular basis of VPA-induced ASD at the single-cell resolution is unclear. Here, we aim to compare the cellular and molecular differences in the hippocampus between male and female prenatal mice with ASD at the single-cell transcriptomic level. The transcriptomes of more than 45,000 cells are assigned to 12 major cell types, including neurons, glial cells, vascular cells, and immune cells. Cell type-specific genes with altered expression after prenatal VPA exposure are analyzed, and the largest number of differentially expressed genes (DEGs) are found in neurons, choroid plexus epithelial cells, and microglia. In microglia, several pathways related to inflammation are found in both males and females, including the tumor necrosis factor (TNF), nuclear factor kappa B (NF-κB), toll-like receptor (TLR), and mitogen-activated protein kinase (MAPK) signaling pathways, which are important for the induction of autistic-like behavior. Additionally, we note that several X-linked genes, including Bex1, Bex3, and Gria3, were among the male-specific DEGs of neurons. This pioneering study describes the landscape of the transcriptome in the hippocampus of autistic mice. The elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.
Topics: Pregnancy; Mice; Animals; Male; Female; Autism Spectrum Disorder; Valproic Acid; Autistic Disorder; Neurons; Inflammation; Disease Models, Animal; Behavior, Animal
PubMed: 37703921
DOI: 10.1016/j.jgg.2023.08.012 -
European Child & Adolescent Psychiatry Apr 2024Autistic children (Autism Spectrum Disorder, ASD) show an increased risk of bullying victimization and often face challenges in communication and peer relationships....
Autistic children (Autism Spectrum Disorder, ASD) show an increased risk of bullying victimization and often face challenges in communication and peer relationships. However, it is unclear to what extent the amount and quality of ASD traits are associated with bullying victimization. This study examined the association of bullying victimization and ASD traits in an epidemiological population of 8-year-old children (n = 4408) using parent and teacher completed Autism Spectrum Screening Questionnaires (ASSQs), both separately and combined. The ASSQ items relating to loneliness and social isolation, lack of co-operating skills, clumsiness and lack of common sense were associated with victimization in the study population. The higher the ASSQ scores, the more the children were victimized: the ASSQ scores increased in parallel with victimization from 0 (0% victimized) to 45 (64% victimized). The victimization rate was 46% in ASD sample, 2% in the total population sample and 2% in the non-ASD population sample. The results enable more targeted means for recognizing potential victimization.
Topics: Child; Humans; Autism Spectrum Disorder; Social Isolation; Parents; Bullying; Crime Victims
PubMed: 37219644
DOI: 10.1007/s00787-023-02228-2 -
Cell Reports Sep 2023Strong evidence from human genetic studies associates the thousand and one amino acid kinase 1 (TAOK1) gene with autism spectrum disorder (ASD). In this work, we...
Strong evidence from human genetic studies associates the thousand and one amino acid kinase 1 (TAOK1) gene with autism spectrum disorder (ASD). In this work, we discovered a de novo frameshifting mutation in TAOK1 within a Chinese ASD cohort. We found that Taok1 haploinsufficiency induces autistic-like behaviors in mice. Importantly, we observed a significant enrichment of Taok1 in the dorsal raphe nucleus (DRN). The haploinsufficiency of Taok1 considerably restrained the activation of DRN neurons during social interactions, leading to the aberrant phosphorylation of numerous proteins. Intriguingly, the genetic deletion of Taok1 in VGlut3-positive neurons of DRN resulted in mice exhibiting autistic-like behaviors. Ultimately, reintroducing wild-type Taok1, but not its kinase-dead variant, into the DRN of adult mice effectively mitigated the autistic-like behaviors associated with Taok1 haploinsufficiency. This work suggests that Taok1, through its influence in the DRN, regulates social interaction behaviors, providing critical insights into the etiology of ASD.
Topics: Humans; Animals; Mice; Autistic Disorder; Autism Spectrum Disorder; Dorsal Raphe Nucleus; Haploinsufficiency; Social Behavior; Protein Serine-Threonine Kinases
PubMed: 37656623
DOI: 10.1016/j.celrep.2023.113078 -
Sao Paulo Medical Journal = Revista... 2024During development, children face a number of demands and cognitive, behavioral, and social challenges necessary for growth. Cognitive skills make individuals competent...
BACKGROUND
During development, children face a number of demands and cognitive, behavioral, and social challenges necessary for growth. Cognitive skills make individuals competent and allow them to interact with their environment.
OBJECTIVE
To identify the cognitive skills that promote better social insertion in children with autism spectrum disorder within 12 months.
DESIGN AND SETTING
Prospective cohort study.
METHODS
In this study, 21 children aged 3-12 years were assessed, and their mothers were interviewed. Children were enrolled in regular or special autistic schools. Twelve months after the first assessment, the same children participated in the second assessment. In individual interviews, mothers provided data by answering the Vineland Adaptive Behavior Scale. Each child was assessed individually using the fourth edition of the Stanford Binet Intelligence Scale 4th Edition.
RESULTS
In the first assessment, the Stanford Binet areas and total scores correlated with the communication domains, daily life abilities, socialization, and total score of the Vineland Scale. After 12 months, a correlation was observed between the Stanford Binet areas and the total and communication domains, daily life abilities, socialization, motor abilities, and total score on the Vineland Scale.
CONCLUSION
Logic mathematics and memory promote better social insertion in children with autism spectrum disorder. General cognitive ability promotes communication.
Topics: Humans; Autism Spectrum Disorder; Prospective Studies; Female; Child; Child, Preschool; Male; Cognition; Social Adjustment; Adaptation, Psychological
PubMed: 38655981
DOI: 10.1590/1516-3180.2023.0184.R1.16022024 -
BMC Psychiatry Jan 2024Observational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them...
BACKGROUND
Observational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety.
METHODS
Bidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (N = 60,653, N = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method.
RESULTS
Bidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy.
CONCLUSIONS
Our study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.
Topics: Humans; Autism Spectrum Disorder; Depressive Disorder, Major; Dermatitis, Atopic; Genome-Wide Association Study; Mendelian Randomization Analysis; Anorexia Nervosa
PubMed: 38172785
DOI: 10.1186/s12888-023-05478-1 -
Biomolecules Apr 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe deficits in social communication and interaction, repetitive movements, abnormal... (Review)
Review
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.
Topics: Autism Spectrum Disorder; Humans; Epigenesis, Genetic; Neuroglia; Valproic Acid; Propionates; Animals; Acetaminophen; Neurons; DNA Methylation
PubMed: 38672454
DOI: 10.3390/biom14040437 -
BMC Neurology Aug 2023Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic...
BACKGROUND
Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis.
METHODS
Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods.
RESULTS
Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling.
CONCLUSIONS
Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.
Topics: Child; Humans; Male; Autism Spectrum Disorder; Exome Sequencing; Pathology, Molecular; Genetic Testing; Microarray Analysis
PubMed: 37543562
DOI: 10.1186/s12883-023-03341-0