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Human Brain Mapping Nov 2023Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging has been widely applied to guide precise repetitive transcranial magnetic...
Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging has been widely applied to guide precise repetitive transcranial magnetic stimulation (rTMS). The left, right, and bilateral dorsolateral prefrontal cortices (DLPFC) have been used as rTMS treatment target regions for autism spectrum disorder (ASD), albeit with moderate efficacy. Thus, we aimed to develop an individualized localization method for rTMS treatment of ASD. We included 266 male ASDs and 297 male typically-developed controls (TDCs) from the Autism Brain Imaging Data Exchange Dataset. The nucleus accumbens (NAc) was regarded as a promising effective region, which was used as a seed and individualized peak FC strength in the DLPFC was compared between ASD and TDC. Correlation analysis was conducted between individualized peak FC strength and symptoms in ASD. We also investigated the spatial distribution of individualized peak FC locations in the DLPFC and conducted voxel-wise analysis to compare NAc-based FC between the two groups. ASD showed stronger peak FC in the right DLPFC related to TDC (Cohen's d = -.19, 95% CI: -0.36 to -0.03, t = -2.30, p = .02). Moreover, negative correlation was found between the peak FC strength in the right DLPFC and Autism Diagnostic Observation Schedule (ADOS) scores, which assessed both the social communication and interaction (r = -.147, p = .04, uncorrected significant), and stereotyped behaviors and restricted interests (r = -.198, p = .02, corrected significant). Peak FC locations varied substantially across participants. No significant differences in NAc-based FC in the DLPFC were found in the voxel-wise comparison. Our study supports the use of individualized peak FC-guided precise rTMS treatment of male ASD. Moreover, stimulating the right DLPFC might alleviate core symptoms of ASD.
Topics: Humans; Male; Transcranial Magnetic Stimulation; Autism Spectrum Disorder; Prefrontal Cortex; Magnetic Resonance Imaging; Brain
PubMed: 37694907
DOI: 10.1002/hbm.26455 -
Journal of Autism and Developmental... Mar 2024This study aimed to learn about the experiences of families of individuals with a dual diagnosis of Down syndrome (DS) and autism spectrum disorder (ASD) (DS-ASD), and...
This study aimed to learn about the experiences of families of individuals with a dual diagnosis of Down syndrome (DS) and autism spectrum disorder (ASD) (DS-ASD), and to document the journey from early concerns to diagnosis and intervention. Caregivers completed an online survey describing their journey raising a child with DS-ASD. Survey responses were analyzed qualitatively and coded into categories to highlight common themes. Stereotypy, severe communication impairments, and behavioral difficulties prompted caregivers to pursue further evaluation. There was a mean 4.65-year gap between first noticing symptoms and receiving an ASD diagnosis. Several therapeutic interventions were identified as beneficial, including behavioral and communication support. Caregivers expressed frustration and described high levels of stress and social isolation. The diagnosis of ASD in children with DS is often delayed, and caregivers' initial concerns are frequently dismissed. Raising a child with DS-ASD can lead to social isolation and elevated caregiver stress. More research is needed to tailor diagnostic algorithms and therapeutic interventions to the unique needs of this patient population. Caregivers yearn for improved understanding of DS-ASD, more targeted therapies and educational programs, and more overall support.
Topics: Child; Humans; Caregivers; Autism Spectrum Disorder; Down Syndrome; Caregiver Burden; Communication
PubMed: 36624226
DOI: 10.1007/s10803-022-05758-x -
Metabolic Brain Disease Jan 2024Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced... (Meta-Analysis)
Meta-Analysis
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.
Topics: Humans; Autism Spectrum Disorder; Autistic Disorder; Biomarkers; Brain; Genomics; Minor Histocompatibility Antigens; Histone Demethylases
PubMed: 38153584
DOI: 10.1007/s11011-023-01322-3 -
Experimental & Molecular Medicine Aug 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.
Topics: Animals; Female; Mice; Pregnancy; Autism Spectrum Disorder; Disease Models, Animal; Proteomics; Ubiquitin-Protein Ligases; Up-Regulation; Valproic Acid; Wnt Signaling Pathway
PubMed: 37524878
DOI: 10.1038/s12276-023-01065-2 -
Nutrients Nov 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects several areas of mental development. The onset of ASD occurs in the first few years of life,... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects several areas of mental development. The onset of ASD occurs in the first few years of life, usually before the age of 3 years. Proper nutrition is important to ensure that an individual's nutrient and energy requirements are met, and it can also have a moderating effect on the progression of the disorder. A systematic database search was conducted as a narrative review to determine whether nutrition and specific diets can potentially alter gastrointestinal symptoms and neurobehavioral disorders. Databases such as Science Direct, PubMed, Scopus, Web of Science (WoS), and Google Scholar were searched to find studies published between 2000 and September 2023 on the relationship between ASD, dietary approaches, and the role of dietary components. The review may indicate that despite extensive research into dietary interventions, there is a general lack of conclusive scientific data about the effect of therapeutic diets on ASD; therefore, no definitive recommendation can be made for any specific nutritional therapy as a standard treatment for ASD. An individualized dietary approach and the dietician's role in the therapeutic team are very important elements of every therapy. Parents and caregivers should work with nutrition specialists, such as registered dietitians or healthcare providers, to design meal plans for autistic individuals, especially those who would like to implement an elimination diet.
Topics: Child; Humans; Child, Preschool; Autism Spectrum Disorder; Diet; Nutritional Status; Autistic Disorder; Nutritional Support
PubMed: 38068711
DOI: 10.3390/nu15234852 -
Medical Sciences (Basel, Switzerland) Nov 2023Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data... (Clinical Trial)
Clinical Trial
Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data suggest that early diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an increasing recognition that ASD might be associated with oxidative stress through several mechanisms including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This open-label pilot study investigates the tolerability and effectiveness of oral supplementation with Opitac gluthathione as a treatment for patients with ASD. The various aspects of glutathione Opitac glutathione bioavailability were examined when administered by oral routes. The absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of this case series suggest that oral glutathione supplementation may improve oxidative markers, but this does not necessarily translate to the observed clinical improvement of subjects with ASD. The study reports a good safety profile of glutathione use, with stomach upset reported in four out of six subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes that a high baseline oxidative burden may make some patients poor responders to glutathione supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors contributing to ASD, and further studies are necessary to investigate other factors, such as impaired neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction.
Topics: Child; Humans; Antioxidants; Autism Spectrum Disorder; Glutathione; Oxidative Stress; Pilot Projects
PubMed: 37987328
DOI: 10.3390/medsci11040073 -
International Journal of Molecular... Feb 2024Autism Spectrum Disorder (ASD) is a disturbance of neurodevelopment with a complicated pathogenesis and unidentified etiology. Many children with ASD have a history of... (Review)
Review
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. Cytokines, essential marker molecules for MC degranulation and therapeutic targets, are also highlighted. Understanding the relationship between ASD and the activation of MCs, as well as the involved molecules and interactions, are the main points contributing to solving the enigma. Key molecules, associated with MCs, may provide new insights to the discovery of drug targets for modeling inflammation in ASD.
Topics: Child; Humans; Mast Cells; Autism Spectrum Disorder; Inflammation; Autistic Disorder; Cytokines
PubMed: 38473898
DOI: 10.3390/ijms25052651 -
Journal of Attention Disorders Dec 2023To evaluate if children and adolescents with a diagnosis of ASD or ADHD have distinct executive function (EF) profiles. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate if children and adolescents with a diagnosis of ASD or ADHD have distinct executive function (EF) profiles.
METHODS
Peer-reviewed articles comparing ASD, ADHD, and typically developing individuals under 19 years of age were identified. The domains evaluated were: working memory, response inhibition, planning, cognitive flexibility, attention, processing speed, and visuospatial abilities.
RESULTS
Fifty-eight articles met inclusion criteria. Analyses were performed on 45 performance metrics from 24 individual tasks. No differences in EF were found between individuals diagnosed with ASD and ADHD. Individuals diagnosed with ASD and ADHD exhibited worse performance in attention, flexibility, visuospatial abilities, working memory, processing speed, and response inhibition than typically developing individuals. Groups did not differ in planning abilities.
CONCLUSION
Children and adolescents with ASD and ADHD have similar EF profiles. Further research is needed to determine if comorbidity accounts for the commonality in executive dysfunction between each disorder.
Topics: Child; Adolescent; Humans; Executive Function; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Memory, Short-Term; Comorbidity
PubMed: 37565325
DOI: 10.1177/10870547231190494 -
PeerJ 2023The fast, intuitive and autonomous system 1 along with the slow, analytical and more logical system 2 constitute the dual system processing model of decision making....
INTRODUCTION
The fast, intuitive and autonomous system 1 along with the slow, analytical and more logical system 2 constitute the dual system processing model of decision making. Whether acting independently or influencing each other both systems would, to an extent, rely on randomness in order to reach a decision. The role of randomness, however, would be more pronounced when arbitrary choices need to be made, typically engaging system 1. The present exploratory study aims to capture the expression of a possible innate randomness mechanism, as proposed by the authors, by trying to isolate system 1 and examine arbitrary decision making in autistic participants with high functioning Autism Spectrum Disorders (ASD).
METHODS
Autistic participants withhigh functioning ASD and an age and gender matched comparison group performed the random number generation task. The task was modified to limit the contribution of working memory and allow any innate randomness mechanisms expressed through system 1, to emerge.
RESULTS
Utilizing a standard analyses approach, the random number sequences produced by autistic individuals and the comparison group did not differ in their randomness characteristics. No significant differences were identified when the sequences were examined using a moving window approach. When machine learning was used, random sequences' features could discriminate the groups with relatively high accuracy.
CONCLUSIONS
Our findings indicate the possibility that individual patterns during random sequence production could be consistent enough between groups to allow for an accurate discrimination between the autistic and the comparison group. In order to draw firm conclusions around innate randomness and further validate our experiment, our findings need to be replicated in a bigger sample.
Topics: Humans; Autistic Disorder; Autism Spectrum Disorder; Memory, Short-Term
PubMed: 37529214
DOI: 10.7717/peerj.15751 -
Environment International Nov 2023The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs).
BACKGROUND
The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs).
OBJECTIVE
To evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae.
METHOD
1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002-2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect.
RESULTS
A total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother-child pairs in this study. β-Hexachlorocyclohexane (β-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of β-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed β-HCH concentration). The median concentration of β-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92-6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of β-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with β-HCH.
CONCLUSIONS
Prenatal exposure to β-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm β-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.
Topics: Pregnancy; Female; Animals; Humans; Zebrafish; Endocrine Disruptors; Prospective Studies; Autism Spectrum Disorder; Environmental Pollutants; Birth Cohort; Norway
PubMed: 37879205
DOI: 10.1016/j.envint.2023.108271