scholarly journals A new test for autism spectrum disorder: metabolic data from different cell types.

Data in Brief ◽  
2021 ◽  
pp. 107598
Author(s):  
Sujata Srikanth ◽  
Lauren Cascio ◽  
Rini Pauly ◽  
Kelly Jones ◽  
Skylar Sorrow ◽  
...  
2019 ◽  
Author(s):  
Charles E. Mordaunt ◽  
Julia M. Jianu ◽  
Ben Laufer ◽  
Yihui Zhu ◽  
Keith W. Dunaway ◽  
...  

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. Since the neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development, we performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth.ResultsWe identified differentially-methylated regions (DMRs) stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development.ConclusionsAt birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD, and provides novel insights for early diagnosis and therapy.


2019 ◽  
Author(s):  
Job O. de Jong ◽  
Ceyda Llapashtica ◽  
Kevin Strauss ◽  
Frank Provenzano ◽  
Yan Sun ◽  
...  

ABSTRACTAutism spectrum disorder (ASD) represents a major public health burden but translating promising treatment findings from preclinical non-human models of ASD to the clinic has remained challenging. The recent development of forebrain organoids generated from human induced pluripotent stem cells (hiPSCs) derived from subjects with brain disorders is a promising method to study human-specific neurobiology, and may facilitate the development of novel therapeutics.In this study, we utilized forebrain organoids generated from hiPSCs derived from patients from the Old Order Amish community with a rare syndromic form of ASD, carrying a homozygous c.3709DelG mutation in CNTNAP2 and healthy controls to investigate the effects of this mutation on cortical embryonic development.Patients carrying the c.3709DelG mutation in CNTNAP2 present with an increased head circumference and brain MRI reveals an increase in gray matter volume. Patient-derived organoids displayed an increase in total volume that was driven by an increased proliferation in neural progenitor cells, leading to an increase in the generation of cortical neuronal and non-neuronal cell types. The observed phenotypes were rescued after correction of the pathogenic mutation using CRISPR-Cas9. RNA sequencing revealed 339 genes differentially expressed between patient- and control-derived organoids of which a subset are implicated in cell proliferation and neurogenesis. Notably, these differentially expressed genes included previously identified ASD-associated genes and are enriched for genes in ASD-associated weighted gene co-expression networks.This work provides a critical step towards understanding the role of CNTNAP2 in human cortical development and has important mechanistic implications for ASD associated with brain overgrowth. This CNTNAP2 organoid model provides opportunity for further mechanistic inquiry and development of new therapeutic strategies for ASD.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Job O. de Jong ◽  
Ceyda Llapashtica ◽  
Matthieu Genestine ◽  
Kevin Strauss ◽  
Frank Provenzano ◽  
...  

AbstractWe utilized forebrain organoids generated from induced pluripotent stem cells of patients with a syndromic form of Autism Spectrum Disorder (ASD) with a homozygous protein-truncating mutation in CNTNAP2, to study its effects on embryonic cortical development. Patients with this mutation present with clinical characteristics of brain overgrowth. Patient-derived forebrain organoids displayed an increase in volume and total cell number that is driven by increased neural progenitor proliferation. Single-cell RNA sequencing revealed PFC-excitatory neurons to be the key cell types expressing CNTNAP2. Gene ontology analysis of differentially expressed genes (DEgenes) corroborates aberrant cellular proliferation. Moreover, the DEgenes are enriched for ASD-associated genes. The cell-type-specific signature genes of the CNTNAP2-expressing neurons are associated with clinical phenotypes previously described in patients. The organoid overgrowth phenotypes were largely rescued after correction of the mutation using CRISPR-Cas9. This CNTNAP2-organoid model provides opportunity for further mechanistic inquiry and development of new therapeutic strategies for ASD.


Autism ◽  
2021 ◽  
pp. 136236132110144
Author(s):  
Carmen Falcone ◽  
Natalie-Ya Mevises ◽  
Tiffany Hong ◽  
Brett Dufour ◽  
Xiaohui Chen ◽  
...  

Autism spectrum disorder is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors. Changes in the number of specific cell types in the cerebral cortex could produce a dramatic alteration in the regulation of cortical circuits, and thus an alteration of behavior. We investigated whether there are layer-specific changes in the number of neurons, astrocytes, and oligodendrocytes in the prefrontal cortex in postmortem human brains from autism spectrum disorder subjects. We quantified the number of specific cell types in the prefrontal cortex (Brodmann areas 9, 46, and 47) of 10 cases with autism spectrum disorder and 10 age-matched control cases. We found that the number of neurons was increased and the number of astrocytes was decreased in layer II of all three prefrontal areas. Area BA47 was most widely affected presenting with an increased number of neurons and a decreased number of astrocytes in layer II and deeper layers of the cortex. Among other possibilities, the alterations in neuron and glial cell number we report here are consistent with a failure of radial glial cells to shift daughter cell production from neurons to astrocytes during prenatal cortical development in autism spectrum disorder. The data provided here are key anatomical findings that shed light on autism spectrum disorder pathogenesis. Lay abstract The cerebral cortex affected with autism spectrum disorder presents changes in the number of neurons and glia cells, possibly leading to a dysregulation of brain circuits and affecting behavior. However, little is known about cell number alteration in specific layers of the cortex in autism spectrum disorder. We found an increase in the number of neurons and a decrease in the number of astrocytes in specific layers of the prefrontal cortex in postmortem human brains from autism spectrum disorder cases. We hypothesize that this may be due to a failure in neural stem cells to shift differentiation from neurons to glial cells during prenatal brain development. These data provide key anatomical findings that contribute to the bases of autism spectrum disorder pathogenesis.


2020 ◽  
Vol 29 (4) ◽  
pp. 1783-1797
Author(s):  
Kelly L. Coburn ◽  
Diane L. Williams

Purpose Neurodevelopmental processes that begin during gestation and continue throughout childhood typically support language development. Understanding these processes can help us to understand the disruptions to language that occur in neurodevelopmental conditions, such as autism spectrum disorder (ASD). Method For this tutorial, we conducted a focused literature review on typical postnatal brain development and structural and functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, and electroencephalography studies of the neurodevelopmental differences that occur in ASD. We then integrated this knowledge with the literature on evidence-based speech-language intervention practices for autistic children. Results In ASD, structural differences include altered patterns of cortical growth and myelination. Functional differences occur at all brain levels, from lateralization of cortical functions to the rhythmic activations of single neurons. Neuronal oscillations, in particular, could help explain disrupted language development by elucidating the timing differences that contribute to altered functional connectivity, complex information processing, and speech parsing. Findings related to implicit statistical learning, explicit task learning, multisensory integration, and reinforcement in ASD are also discussed. Conclusions Consideration of the neural differences in autistic children provides additional scientific support for current recommended language intervention practices. Recommendations consistent with these neurological findings include the use of short, simple utterances; repetition of syntactic structures using varied vocabulary; pause time; visual supports; and individualized sensory modifications.


2020 ◽  
Vol 29 (2) ◽  
pp. 890-902
Author(s):  
Lynn Kern Koegel ◽  
Katherine M. Bryan ◽  
Pumpki Lei Su ◽  
Mohini Vaidya ◽  
Stephen Camarata

Purpose The purpose of this systematic review was to identify parent education procedures implemented in intervention studies focused on expressive verbal communication for nonverbal (NV) or minimally verbal (MV) children with autism spectrum disorder (ASD). Parent education has been shown to be an essential component in the habilitation of individuals with ASD. Parents of individuals with ASD who are NV or MV may particularly benefit from parent education in order to provide opportunities for communication and to support their children across the life span. Method ProQuest databases were searched between the years of 1960 and 2018 to identify articles that targeted verbal communication in MV and NV individuals with ASD. A total of 1,231 were evaluated to assess whether parent education was implemented. We found 36 studies that included a parent education component. These were reviewed with regard to (a) the number of participants and participants' ages, (b) the parent education program provided, (c) the format of the parent education, (d) the duration of the parent education, (e) the measurement of parent education, and (f) the parent fidelity of implementation scores. Results The results of this analysis showed that very few studies have included a parent education component, descriptions of the parent education programs are unclear in most studies, and few studies have scored the parents' implementation of the intervention. Conclusions Currently, there is great variability in parent education programs in regard to participant age, hours provided, fidelity of implementation, format of parent education, and type of treatment used. Suggestions are made to provide both a more comprehensive description and consistent measurement of parent education programs.


2020 ◽  
Vol 29 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Allison Gladfelter ◽  
Cassidy VanZuiden

Purpose Although repetitive speech is a hallmark characteristic of autism spectrum disorder (ASD), the contributing factors that influence repetitive speech use remain unknown. The purpose of this exploratory study was to determine if the language context impacts the amount and type of repetitive speech produced by children with ASD. Method As part of a broader word-learning study, 11 school-age children with ASD participated in two different language contexts: storytelling and play. Previously collected language samples were transcribed and coded for four types of repetitive speech: immediate echolalia, delayed echolalia, verbal stereotypy, and vocal stereotypy. The rates and proportions of repetitive speech were compared across the two language contexts using Wilcoxon signed-ranks tests. Individual characteristics were further explored using Spearman correlations. Results The children produced lower rates of repetitive speech during the storytelling context than the play-based context. Only immediate echolalia differed between the two contexts based on rate and approached significance based on proportion, with more immediate echolalia produced in the play-based context than in the storytelling context. There were no significant correlations between repetitive speech and measures of social responsiveness, expressive or receptive vocabulary, or nonverbal intelligence. Conclusions The children with ASD produced less immediate echolalia in the storytelling context than in the play-based context. Immediate echolalia use was not related to social skills, vocabulary, or nonverbal IQ scores. These findings offer valuable insights into better understanding repetitive speech use in children with ASD.


2020 ◽  
Vol 29 (2) ◽  
pp. 586-596 ◽  
Author(s):  
Kaitlyn A. Clarke ◽  
Diane L. Williams

Purpose The aim of this research study was to examine common practices of speech-language pathologists (SLPs) who work with children with autism spectrum disorder (ASD) with respect to whether or not SLPs consider processing differences in ASD or the effects of input during their instruction. Method Following a qualitative research method, how SLPs instruct and present augmentative and alternative communication systems to individuals with ASD, their rationale for method selection, and their perception of the efficacy of selected interventions were probed. Semistructured interviews were conducted as part of an in-depth case report with content analysis. Results Based on completed interviews, 4 primary themes were identified: (a) instructional method , (b) input provided , (c) decision-making process , and (d) perceived efficacy of treatment . Additionally, one secondary theme, training and education received , was identified . Conclusions Clinicians reported making decisions based on the needs of the child; however, they also reported making decisions based on the diagnostic category that characterized the child (i.e., ASD). The use of modeling when teaching augmentative and alternative communication to individuals with ASD emerged as a theme, but variations in the method of modeling were noted. SLPs did not report regularly considering processing differences in ASD, nor did they consider the effects of input during instruction.


2020 ◽  
Vol 5 (1) ◽  
pp. 314-325
Author(s):  
Kimberly F. Frazier ◽  
Jessica Collier ◽  
Rachel Glade

Background The aim of this study was to determine the clinical efficacy of combining self-management strategies and a social thinking approach to address the social performance and executive function of an adolescent female with autism spectrum disorder. Method This research examined the effects of a social knowledge training program, “Think Social,” as well as strategies to improve higher order cognitive abilities. Results and Conclusion Although quantitative improvement was not found, several qualitative gains in behavior were noted for the participants of this study, suggesting a benefit from using structured environmental cues of self-management strategies, as well as improved social understanding through social cognitive training.


Sign in / Sign up

Export Citation Format

Share Document