scholarly journals Insufficient Evidence for “Autism-Specific” Genes

2020 ◽  
Author(s):  
Scott M. Myers ◽  
Thomas D. Challman ◽  
Raphael Bernier ◽  
Thomas Bourgeron ◽  
Wendy K. Chung ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Rare Variant ◽  
Effect Size ◽  
Neurodevelopmental Disorders ◽  
Rare Variants ◽  
Autism Spectrum ◽  
Insufficient Evidence ◽  
Large Effect Size ◽  
Published Evidence ◽  
Contradictory Data

Despite the evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review recent efforts to identify “autism-specific” genes, which focus on rare variants of large effect size that are thought to account for the observed phenotype in participants, present a divergent interpretation of the published evidence, and provide additional contradictory data. There is currently insufficient evidence to establish ASD-specificity of any genes based on large-effect rare variant data.

Handedness and depression: a meta-analysis across 87 studies

2021 ◽  
Author(s):  
Julian Packheiser ◽  
Judith Schmitz ◽  
Gesa Berretz ◽  
Lena Sophie Pfeifer ◽  
Clara Celina Stein ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Effect Size ◽  
Neurodevelopmental Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Precise Estimate ◽  
Brain Lateralization ◽  
Functional Brain ◽  
Depression Disorders

Alterations in functional brain lateralization, often indicated by an increased prevalence of left- and/or mixed-handedness, have been demonstrated in several psychiatric and neurodevelopmental disorders like schizophrenia or autism spectrum disorder. For depression, however, this relationship is largely unclear. While a few studies found evidence that handedness and depression are associated, both the effect size and the direction of this association remain elusive. Here, we collected data from 87 studies totaling 35,501 individuals diagnosed with depression disorders to provide a precise estimate of differences in left-, mixed- and non-right-handedness between depressed and healthy samples. We found no differences in left- (OR = 1.04, p = .384), mixed- (OR = 1.64, p = .060) or non-right-handedness (OR = 1.05, p = .309) between the two groups. We could thus find no link between handedness and depression on the meta-analytical level.

scholarly journals Contribution of Multiple Inherited Variants to Autism Spectrum Disorder (ASD) in a Family with 3 Affected Siblings

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1053
Author(s):  
Jasleen Dhaliwal ◽  
Ying Qiao ◽  
Kristina Calli ◽  
Sally Martell ◽  
Simone Race ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Rare Variants ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Compound Heterozygous ◽  
Variable Effect ◽  
Gabaergic Neurotransmission ◽  
High Heritability ◽  
Compound Heterozygous Variants

Autism Spectrum Disorder (ASD) is the most common neurodevelopmental disorder in children and shows high heritability. However, how inherited variants contribute to ASD in multiplex families remains unclear. Using whole-genome sequencing (WGS) in a family with three affected children, we identified multiple inherited DNA variants in ASD-associated genes and pathways (RELN, SHANK2, DLG1, SCN10A, KMT2C and ASH1L). All are shared among the three children, except ASH1L, which is only present in the most severely affected child. The compound heterozygous variants in RELN, and the maternally inherited variant in SHANK2, are considered to be major risk factors for ASD in this family. Both genes are involved in neuron activities, including synaptic functions and the GABAergic neurotransmission system, which are highly associated with ASD pathogenesis. DLG1 is also involved in synapse functions, and KMT2C and ASH1L are involved in chromatin organization. Our data suggest that multiple inherited rare variants, each with a subthreshold and/or variable effect, may converge to certain pathways and contribute quantitatively and additively, or alternatively act via a 2nd-hit or multiple-hits to render pathogenicity of ASD in this family. Additionally, this multiple-hits model further supports the quantitative trait hypothesis of a complex genetic, multifactorial etiology for the development of ASDs.

scholarly journals Graph Ricci Curvatures Reveal Disease-related Changes in Autism Spectrum Disorder

2021 ◽  
Author(s):  
Pavithra Elumalai ◽  
Yasharth Yadav ◽  
Nitin Williams ◽  
Emil Saucan ◽  
Jürgen Jost ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Resting State ◽  
Neurodevelopmental Disorders ◽  
Data Exchange ◽  
Meta Analysis ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
The Brain

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders that pose a significant global health burden. Measures from graph theory have been used to characterise ASD-related changes in resting-state fMRI functional connectivity networks (FCNs), but recently developed geometry-inspired measures have not been applied so far. In this study, we applied geometry-inspired graph Ricci curvatures to investigate ASD-related changes in resting-state fMRI FCNs. To do this, we applied Forman-Ricci and Ollivier-Ricci curvatures to compare networks of ASD and healthy controls (N = 1112) from the Autism Brain Imaging Data Exchange I (ABIDE-I) dataset. We performed these comparisons at the brain-wide level as well as at the level of individual brain regions, and further, determined the behavioral relevance of region-specific differences with Neurosynth meta-analysis decoding. We found brain-wide ASD-related differences for both Forman-Ricci and Ollivier-Ricci curvatures. For Forman-Ricci curvature, these differences were distributed across 83 of the 200 brain regions studied, and concentrated within the Default Mode, Somatomotor and Ventral Attention Network. Meta-analysis decoding identified the brain regions showing curvature differences as involved in social cognition, memory, language and movement. Notably, comparison with results from previous non-invasive stimulation (TMS/tDCS) experiments revealed that the set of brain regions showing curvature differences overlapped with the set of brain regions whose stimulation resulted in positive cognitive or behavioural outcomes in ASD patients. These results underscore the utility of geometry-inspired graph Ricci curvatures in characterising disease-related changes in ASD, and possibly, other neurodevelopmental disorders.

Talentos e Aptidões: Um olhar sobre o Autismo

2021 ◽  
Author(s):  
Jaime Lin
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Educational Environment ◽  
Clinical Heterogeneity ◽  
Economic Costs ◽  
The World ◽  
Medical Term ◽  
Patterns Of Behavior ◽  
The Media

Autism is a medical term that encompasses a broad spectrum of neurodevelopmental disorders characterized by impaired reciprocal socialization and communication, often accompanied by restricted or repetitive patterns of behavior and interests. Due to the enlargement in the clinical diagnostic boundaries and the increased awareness of autism spectrum disorder (ASD), the world has seen a dramatic increase in its prevalence during the last two decades. ASD is currently considered one of the most common neurodevelopmental disorders worldwide. Frequently reported in terms of comorbidities, disabilities, burden and economic costs, the talents, gifts and abilities of people within the autistic spectrum only reaches the media when it amazes the audience. In this review, we want show that the high clinical heterogeneity found in autism can also be applied to the gifts and abilities, and that it must be nurtured with appropriate developmental, educational environment and above all, support and hope.

Automatic Detection and Assessment of Autism Spectrum Disorder

2021 ◽  
pp. 396-425
Author(s):  
Thanga Aarthy M. ◽  
Menaka R. ◽  
Karthik R.
Keyword(s):  
Autism Spectrum Disorder ◽  
Early Detection ◽  
Early Diagnosis ◽  
Neurodevelopmental Disorders ◽  
Pathological Condition ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Attention Deficit Hyperactive Disorder ◽  
Clinical Methods

Children with neurodevelopmental disorders are increasing gradually every year. One in 100 children are diagnosed with brain function disorder. There are wide categories of disorder such as attention deficit hyperactive disorder, learning, autism spectrum disorder (ASD), etc. In this work, the focus is on ASD, its clinical methods, and analysis in various research works. ASD is a neurodevelopmental disorder which affects the intellectual functioning, social interaction (adaptive behavior), and has a specific obsessive interest. At present, there is no known cure for ASD, but the level of the pathological condition can be reduced when it is detected early. Early detection is tough and challenging till date. Many researches were carried out to ease the early detection for clinicians. Each method has its own merits and demerits. This chapter reviews and condenses various research works and their efficacy in analysis for the early diagnosis and improvement in children with autism.

scholarly journals Salivary Cytokine Profile as a Possible Predictor of Autism Spectrum Disorder

2020 ◽  
Vol 9 (10) ◽  
pp. 3101 ◽  
Author(s):  
Joanna Samborska-Mazur ◽  
Anna Kostiukow ◽  
Izabela Miechowicz ◽  
Dorota Sikorska ◽  
Rafał Rutkowski ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Typically Developing ◽  
Monocyte Chemoattractant Protein 1 ◽  
Children With Asd ◽  
Cytokine Levels ◽  
Factor Α ◽  
Gait Disturbances

Autism spectrum disorder (ASD) is characterized by neurodevelopmental disorders and alterations in immune function and cytokine levels. The aim of this study is to determine the salivary levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES), and Eotaxin in children with ASD and in healthy controlsto assess their predictive potential. We explored correlations between the cytokine levels and the neurodevelopmental disorders related to ASD. The study comprised 19 children with ASD and 19 typically developing (TD) ones. We analyzed salivary levels of IL-1β, IL-6, IL-8, TNFα, MCP-1, RANTES, and eotaxin on Luminex with custom-designed 7-plex kits. The level of RANTES in ASD children was significantly lower than those of TD. In TDs, the salivary levels of IL-1β, MCP-1, and TNFα correlated positively with age. In ASD, the cytokine levels did not correlate with age. There were statistically significant differences between the RANTES level and aggression and gait disturbances, between IL-8 level and fixations/stimulations, and between IL-1β level and no active speech. The levels of the cytokine detected can manifest both systemic and local changes related to ASD. The cytokine pattern cannot be used as a sole ASD predictor, but the salivary levels may be helpful in categorizing the ASD subtype.

scholarly journals Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristina Cheroni ◽  
Nicolò Caporale ◽  
Giuseppe Testa
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Neurodevelopmental Disorders ◽  
Chemical Exposure ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Spectrum Disorder ◽  
Regulatory Pathways ◽  
Genes And Environment ◽  
Analytical Approaches

Abstract 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.

Sign in / Sign up

Export Citation Format

Share Document