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The Clinical Neuropsychologist Jul 2022: Autism spectrum disorder (ASD) in very young children with significant cognitive impairment is difficult to diagnose, depriving them of the earliest opportunities for...
: Autism spectrum disorder (ASD) in very young children with significant cognitive impairment is difficult to diagnose, depriving them of the earliest opportunities for autism-specific intervention. This study delineated specific symptoms in this group, compared to symptoms in children with Global Developmental Delay (GDD) and in ASD with milder developmental delays.: Autism Diagnostic Observation Schedule, 2nd Edition, Toddler Module revealed symptoms in three groups of toddlers, with mean ages of 17-20 months: (1) ASD and cognitive/language functioning below the 12-month level (ASD-MA < 12 mos; = 28), (2) GDD ( = 27), and (3) ASD and cognitive/language functioning at or above the 12-month level (ASD-MA ≥ 12 mos; = 29). Logistic regression models were fit to control for developmental level. : Items in all domains (social interaction, communication, repetitive movements) discriminated ASD-MA < 12 mos from GDD. The two ASD groups, matched for age but differing on developmental level, showed strikingly similar ASD symptomatology. Conclusion: ADOS-2 symptoms differentiated ASD-MA < 12 mos from GDD, after controlling for cognitive impairment. Symptoms in the two ASD groups were minimally related to developmental level. The ADOS-2 Toddler Module successfully captured ASD symptomatology even in children whose developmental level was below the recommended ADOS-2 cutoff of 12 months, which may increase their access to early ASD-specific intervention.
Topics: Autism Spectrum Disorder; Child, Preschool; Cognition; Humans; Infant; Intelligence; Logistic Models; Neuropsychological Tests
PubMed: 34762009
DOI: 10.1080/13854046.2021.1998634 -
Journal of Neurodevelopmental Disorders Jun 2019The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism... (Review)
Review
BACKGROUND
The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment.
MAIN BODY
Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-β signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-β, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD.
CONCLUSION
The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods.
Topics: Autism Spectrum Disorder; Humans; Signal Transduction
PubMed: 31202261
DOI: 10.1186/s11689-019-9268-y -
Zoological Research Nov 2021Autism spectrum disorder (ASD) is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors. It is widely accepted that genetic... (Review)
Review
Autism spectrum disorder (ASD) is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors. It is widely accepted that genetic and environmental factors solely or in combination cause ASD. However, the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature. To better understand the pathogenesis of ASD, various animal models have been generated, which can be generally divided into genetic, environment-induced, and idiopathic animal models. In this review, we summarize the common animals used for ASD study and then discuss the applications, clinical insights, as well as challenges and prospects of current ASD animal models.
Topics: Animals; Autism Spectrum Disorder; Disease Models, Animal; Humans
PubMed: 34755500
DOI: 10.24272/j.issn.2095-8137.2021.251 -
Molecular Autism Nov 2020The heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological...
BACKGROUND
The heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological etiologies, genetics, neural systems, neurocognitive attributes and clinical subtypes or phenotypes has been observed across individuals with ASD.
METHODS
In this study, we aim to investigate the heterogeneity in ASD from a multimodal brain imaging perspective. The Autism Diagnostic Observation Schedule (ADOS) was used as a reference to guide functional and structural MRI fusion. DSM-IV-TR diagnosed Asperger's disorder (n = 79), pervasive developmental disorder-not otherwise specified [PDD-NOS] (n = 58) and Autistic disorder (n = 92) from ABIDE II were used as discovery cohort, and ABIDE I (n = 400) was used for replication.
RESULTS
Dorsolateral prefrontal cortex and superior/middle temporal cortex are the primary common functional-structural covarying cortical brain areas shared among Asperger's, PDD-NOS and Autistic subgroups. Key differences among the three subtypes are negative functional features within subcortical brain areas, including negative putamen-parahippocampus fractional amplitude of low-frequency fluctuations (fALFF) unique to the Asperger's subtype; negative fALFF in anterior cingulate cortex unique to PDD-NOS subtype; and negative thalamus-amygdala-caudate fALFF unique to the Autistic subtype. Furthermore, each subtype-specific brain pattern is correlated with different ADOS subdomains, with social interaction as the common subdomain. The identified subtype-specific patterns are only predictive for ASD symptoms manifested in the corresponding subtypes, but not the other subtypes.
CONCLUSIONS
Although ASD has a common neural basis with core deficits linked to social interaction, each ASD subtype is strongly linked to unique brain systems and subdomain symptoms, which may help to better understand the underlying mechanisms of ASD heterogeneity from a multimodal neuroimaging perspective.
LIMITATIONS
This study is male based, which cannot be generalized to the female or the general ASD population.
Topics: Adolescent; Autism Spectrum Disorder; Brain Mapping; Case-Control Studies; Child; Cohort Studies; Female; Humans; Magnetic Resonance Imaging; Male; Models, Biological; Reproducibility of Results
PubMed: 33208189
DOI: 10.1186/s13229-020-00397-4 -
BMC Pediatrics Sep 2023Autism spectrum disorder (ASD) is a neurodevelopmental disability associated with deficiency in social interaction, unusual development of social communication, and...
BACKGROUND
Autism spectrum disorder (ASD) is a neurodevelopmental disability associated with deficiency in social interaction, unusual development of social communication, and restricted or repetitive behaviors, interests and activities. This study aimed to describe management of pediatric ASD in Cameroon, a resource-constrained Central Africa country.
METHODS
A retrospective study was conducted between December 2021 and May 2022 at the Pediatrics department of a reference hospital in the town of Douala. Data of interest of children with ASD were collected through eligible medical records and telephone discussions with their parents/guardians.
RESULTS
Medical records of 145 children with ASD aged 2-15 years were included in the study, giving a hospital ASD prevalence of 3.7%. Time delay between parental concerns and hospital management was specified in 69 (47.58%) children, and among them 38 (55.07%) had a mean delay ± SD was less than five months. Children were mainly males (76%) and aged 4-5 years (37.93%), with mean age ± SD of 44.4 ± 22.2 months old. The main consultation reason was delayed language development (100%). Mean time delay between parental concerns and the first medical consultation was 18 months (range 1-60 month). Attention deficit hyperactivity disorder were found in 68.18% of children aged ≥ 6 years old. Neuropsychology (66.2%) was the most frequently used intervention. Some children were treated using traditional medicine.
CONCLUSIONS
Management of pediatric ASD is strongly influenced by socioeconomic and cultural context. It is crucial to implement behavioral change campaigns in community, organize training sessions to medical staff on diagnosis and treatment of ASD, and provide specialized centers with skilled staff and equipped material.
Topics: Male; Humans; Child; Infant; Child, Preschool; Female; Cameroon; Autism Spectrum Disorder; Retrospective Studies; Hospitals; Language
PubMed: 37704945
DOI: 10.1186/s12887-023-04242-4 -
Molecular Autism Sep 2020The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes,... (Review)
Review
The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals' genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment.
Topics: Autism Spectrum Disorder; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Risk Factors; Systematic Reviews as Topic
PubMed: 32912338
DOI: 10.1186/s13229-020-00370-1 -
Journal of Autism and Developmental... Jun 2022This study investigated motor preparation and action-consequence prediction using the lateralized readiness potential (LRP). Motor impairments are common in autism...
This study investigated motor preparation and action-consequence prediction using the lateralized readiness potential (LRP). Motor impairments are common in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. Alterations in predictive processes may impact motor planning. Whether motor planning deficits are characteristic of ASD broadly or magnified in the context of co-morbid ADHD is unclear. ASD children with (ASD + ADHD; n = 12) and without (ASD - ADHD; n = 9) comorbid ADHD and typical controls (n = 29) performed voluntary motor actions that either did or did not result in auditory consequences. ASD - ADHD children demonstrated LRP enhancement when their action produced an effect while ASD + ADHD children had attenuated responses regardless of action-effect pairings. Findings suggest influence of ADHD comorbidity on motor preparation and prediction in ASD.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Comorbidity; Humans
PubMed: 34160725
DOI: 10.1007/s10803-021-05130-5 -
JPMA. the Journal of the Pakistan... Sep 2023
Topics: Humans; Autism Spectrum Disorder
PubMed: 37817726
DOI: 10.47391/JPMA.8207 -
Revista Espanola de Sanidad... 2023Autism is a neurodevelopmental disorder characterized by intolerance of change, empathy deficits, misunders- tandings, and emotional dysregulation. Core symptoms can...
INTRODUCTION
Autism is a neurodevelopmental disorder characterized by intolerance of change, empathy deficits, misunders- tandings, and emotional dysregulation. Core symptoms can determine criminal behaviour and subsequent interactions with the penal system. A significant presence of such symptoms is detected in forensic settings. The objective of this study is to analyze the characteristics of autism within the prison context, summarizing and updating the knowledge in this field.
MATERIAL AND METHOD
Systematic review through databases on studies that analyze the socio-demographic, clinical, and judi- cial characteristics of prisoners diagnosed with autism spectrum disorder.
RESULTS
Autistic traits constitute an independent risk factor for incarceration. Those inmates with autism spectrum disorder frequently present a psychiatric comorbidity, especially substance use disorder, psychotic disorders, and other neuro-develop- mental disorders. They are associated with a greater probability of self-harming thoughts and disruptive behaviours, which are not predicted by the usual evaluation tools.
DISCUSSION
Prisoners with autism spectrum disorder have a differential socio-demographic, clinical, and criminal profile. A specific approach that is different from the one provided for neurotypical prisoners should be offered to these inmates. In- frastructures should be adapted to reduce fragility, make the environment more flexible and specific methods for evaluation and treatment should be developed.
Topics: Humans; Prisons; Autism Spectrum Disorder; Prisoners; Psychotic Disorders; Autistic Disorder
PubMed: 37335535
DOI: 10.18176/resp.00064 -
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