scholarly journals IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin

2019 ◽  
Vol 116 (43) ◽  
pp. 21659-21665 ◽  
Author(s):  
Irene Tsilioni ◽  
Arti B. Patel ◽  
Harry Pantazopoulos ◽  
Sabina Berretta ◽  
Pio Conti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Proinflammatory Cytokines ◽  
Dorsolateral Prefrontal Cortex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Human Microglia ◽  
Children With Asd ◽  
Dorsolateral Prefrontal

Autism spectrum disorder (ASD) does not have a distinct pathogenesis or effective treatment. Increasing evidence supports the presence of immune dysfunction and inflammation in the brains of children with ASD. In this report, we present data that gene expression of the antiinflammatory cytokine IL-37, as well as of the proinflammatory cytokines IL-18 and TNF, is increased in the amygdala and dorsolateral prefrontal cortex of children with ASD as compared to non-ASD controls. Gene expression of IL-18R, which is a receptor for both IL-18 and IL-37, is also increased in the same brain areas of children with ASD. Interestingly, gene expression of the NTR3/sortilin receptor is reduced in the amygdala and dorsolateral prefrontal cortex. Pretreatment of cultured human microglia from normal adult brains with human recombinant IL-37 (1 to 100 ng/mL) inhibits neurotensin (NT)-stimulated secretion and gene expression of IL-1β and CXCL8. Another key finding is that NT, as well as the proinflammatory cytokines IL-1β and TNF increase IL-37 gene expression in cultured human microglia. The data presented here highlight the connection between inflammation and ASD, supporting the development of IL-37 as a potential therapeutic agent of ASD.

scholarly journals Transcranial Direct Current Stimulation (tDCS) over the Left Dorsal Lateral Prefrontal Cortex in Children with Autism Spectrum Disorder (ASD)

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiujun Qiu ◽  
Xuejun Kong ◽  
Jihan Li ◽  
Jie Yang ◽  
Yiting Huang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sleep Habits ◽  
Lateral Prefrontal Cortex ◽  
Direct Current Stimulation ◽  
Children With Asd

Recently, transcranial direct current stimulation (tDCS) has been applied to relieve symptoms in individuals with autism spectrum disorder (ASD). In this prospective, parallel, single-blinded, randomized study, we investigate the modulation effect of three-week tDCS treatment at the left dorsal lateral prefrontal cortex (DLPFC) in children with ASD. 47 children with ASD were enrolled, and 40 (20 in each group) completed the study. The primary outcomes are Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised (RBS-R). We found that children with ASD can tolerate three-week tDCS treatment with no serious adverse events detected. A within-group comparison showed that real tDCS, but not sham tDCS, can significantly reduce the scores of CARS, Children’s Sleep Habits Questionnaire (CSHQ), and general impressions in CARS (15th item). Real tDCS produced significant score reduction in the CSHQ and in CARS general impressions when compared to the effects of sham tDCS. The pilot study suggests that three-week left DLPFC tDCS is well-tolerated and may hold potential in relieving some symptoms in children with ASD.

scholarly journals Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

2020 ◽  
Author(s):  
Kristen R. Maynard ◽  
Leonardo Collado-Torres ◽  
Lukas M. Weber ◽  
Cedric Uytingco ◽  
Brianna K. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Web Application ◽  
Dorsolateral Prefrontal Cortex ◽  
Large Scale ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Sequencing Data ◽  
Dorsolateral Prefrontal ◽  
Transcriptomics Data

AbstractWe used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex (DLPFC). We identified extensive layer-enriched expression signatures, and refined associations to previous laminar markers. We overlaid our laminar expression signatures onto large-scale single nuclei RNA sequencing data, enhancing spatial annotation of expression-driven clusters. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially-defined expression. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions where morphological architecture is not as well-defined as cortical laminae. We lastly created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research (http://research.libd.org/spatialLIBD).

scholarly journals IL-38 inhibits microglial inflammatory mediators and is decreased in amygdala of children with autism spectrum disorder

2020 ◽  
Vol 117 (28) ◽  
pp. 16475-16480 ◽  
Author(s):  
Irene Tsilioni ◽  
Harry Pantazopoulos ◽  
Pio Conti ◽  
Susan E. Leeman ◽  
Theoharis C. Theoharides
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Interactions ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
University Of Maryland ◽  
Human Microglia ◽  
Adult Human ◽  
Children With Asd ◽  
The University

Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia to secrete the proinflammatory molecules IL-1β and CXCL8. This process is inhibited by the cytokine IL-37. Another cytokine, IL-38, has been reported to have antiinflammatory actions. In this report, we show that pretreatment of cultured adult human microglia with recombinant IL-38 (aa3-152, 1–100 ng/mL) inhibits (P< 0.0001) NT-stimulated (10 nM) secretion of IL-1β (at 1 ng/mL) and CXCL8 (at 100 ng/mL). In fact, IL-38 (aa3-152, 1 ng/mL) is more potent than IL-37 (100 ng/mL). Here, we report that pretreatment with IL-38 (100 ng/mL) of embryonic microglia (HMC3), in which secretion of IL-1β was undetectable, inhibits secretion of CXCL8 (P= 0.004). Gene expression of IL-38 and its receptor IL-36R are decreased (P= 0.001 andP= 0.04, respectively) in amygdala from patients with ASD (n= 8) compared to non-ASD controls (n= 8), obtained from the University of Maryland NeuroBioBank. IL-38 is increased (P= 0.03) in the serum of children with ASD. These findings indicate an important role for IL-38 in the inhibition of activation of human microglia, thus supporting its development as a treatment approach for ASD.

scholarly journals Effortful Control and Prefrontal Cortex Functioning in Children with Autism Spectrum Disorder: An fNIRS Study

2020 ◽  
Vol 10 (11) ◽  
pp. 880
Author(s):  
Karthikeyan Krishnamurthy ◽  
Michael K. Yeung ◽  
Agnes S. Chan ◽  
Yvonne M. Y. Han
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Effortful Control ◽  
Near Infrared ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Neural Basis ◽  
Functional Near Infrared Spectroscopy ◽  
Children With Asd ◽  
Back Task

Effortful control (EC) is an important dimension of temperament, but is impaired in autism spectrum disorder (ASD). While EC is associated with the prefrontal cortex (PFC) functioning in typically developing (TD) children, it is unclear whether EC deficits are associated with PFC dysfunction in ASD. This study examines the relationship between EC and PFC activation and connectivity in children with high-functioning ASD. Thirty-nine right-handed children (ASD: n = 20; TD: n = 19) aged 8–12 years were recruited. The EC level was assessed with the Early Adolescent Temperament Questionnaire—Revised (EATQ-R), and PFC functioning, in terms of activation and connectivity during a frontal-sensitive (n-back) task, was assessed using functional near-infrared spectroscopy (fNIRS). Children with ASD showed a significant deficit in EC and its related constructs (i.e., executive, and socioemotional functions) compared to TD controls. They also showed significantly increased overall PFC activation and reduced right frontal connectivity during the n-back task. Among children with ASD, the EC level correlated significantly with neither PFC activation nor connectivity; it significantly correlated with social functioning only. This study demonstrated EC deficits and altered PFC functioning in children with ASD, but the exact neural basis of EC deficits remains to be determined.

The Influence of Language Context on Repetitive Speech Use in Children With Autism Spectrum Disorder

2020 ◽  
Vol 29 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Allison Gladfelter ◽  
Cassidy VanZuiden
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Individual Characteristics ◽  
Receptive Vocabulary ◽  
Spectrum Disorder ◽  
School Age Children ◽  
Social Responsiveness ◽  
Contributing Factors ◽  
Children With Asd ◽  
Language Context

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.

scholarly journals Parents’ Perceptions of Early Interventions and Related Services for Children with Autism Spectrum Disorder in Saudi Arabia

2016 ◽  
Vol 9 (10) ◽  
pp. 128 ◽  
Author(s):  
Faihan Alotaibi ◽  
Nabil Almalki
Keyword(s):  
Autism Spectrum Disorder ◽  
Saudi Arabia ◽  
Early Intervention ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Early Interventions ◽  
Related Services ◽  
Children With Asd ◽  
The Government

<p class="apa">The present study sought to examine parents’ perceptions of early interventions and related services for children with autism spectrum disorder (ASD) in Saudi Arabia. In this study a survey was distributed to a sample of 80 parents with children who have ASD. Parents also were asked open-ended questions to enable them to provide suggestions. The findings indicate that parents have varying perceptions of early interventions and related services. However, they seem to agree that these services are important in assisting their children. Accordingly, parents have suggested that the government needs to increase these services by providing more centers for children with ASD in Saudi Arabia, providing more specialists to deal with children with ASD, promoting inclusion in regular schools and providing more information on early intervention.</p>

scholarly journals Implication of the Sensory Environment in Children with Autism Spectrum Disorder: Perspectives from School

2021 ◽  
Vol 18 (14) ◽  
pp. 7670
Author(s):  
Ana Gentil-Gutiérrez ◽  
José Luis Cuesta-Gómez ◽  
Paula Rodríguez-Fernández ◽  
Jerónimo Javier González-Bernal
Keyword(s):  
Autism Spectrum Disorder ◽  
Sensory Processing ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sensory Profile ◽  
School Factors ◽  
Cross Sectional ◽  
Sensory Stimuli ◽  
Children With Asd

(1) Background: Children with Autism Spectrum Disorder (ASD) frequently have difficulties in processing sensory information, which is a limitation when participating in different contexts, such as school. The objective of the present study was to compare the sensory processing characteristics of children with ASD in the natural context of school through the perception of professionals in the field of education, in comparison with neurodevelopmental children (2) Methods: A cross-sectional descriptive study as conducted with study population consisting of children between three and ten years old, 36 of whom were diagnosed with ASD and attended the Autismo Burgos association; the remaining 24 had neurotypical development. The degree of response of the children to sensory stimuli at school was evaluated using the Sensory Profile-2 (SP-2) questionnaire in its school version, answered by the teachers. (3) Results: Statistically significant differences were found in sensory processing patterns (p = 0.001), in sensory systems (p = 0.001) and in school factors (p = 0.001). Children with ASD who obtained worse results. (4) Conclusions: Children with ASD are prone to present sensory alterations in different contexts, giving nonadapted behavioral and learning responses.

scholarly journals Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuta Yoshino ◽  
Bhaskar Roy ◽  
Nilesh Kumar ◽  
M. Shahid Mukhtar ◽  
Yogesh Dwivedi
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Gene Network ◽  
Nervous System Development ◽  
Network Analyses ◽  
Dorsolateral Prefrontal ◽  
Total Fraction ◽  
Transcriptomic Changes

AbstractDisrupted synaptic plasticity is the hallmark of major depressive disorder (MDD), with accompanying changes at the molecular and cellular levels. Often, the maladaptive molecular changes at the synapse are the result of global transcriptional reprogramming dictated by activity-dependent synaptic modulation. Thus far, no study has directly studied the transcriptome-wide expression changes locally at the synapse in MDD brain. Here, we have examined altered synaptic transcriptomics and their functional relevance in MDD with a focus on the dorsolateral prefrontal cortex (dlPFC). RNA was isolated from total fraction and purified synaptosomes of dlPFC from well-matched 15 non-psychiatric controls and 15 MDD subjects. Transcriptomic changes in synaptic and total fractions were detected by next-generation RNA-sequencing (NGS) and analyzed independently. The ratio of synaptic/total fraction was estimated to evaluate a shift in gene expression ratio in MDD subjects. Bioinformatics and network analyses were used to determine the biological relevance of transcriptomic changes in both total and synaptic fractions based on gene–gene network, gene ontology (GO), and pathway prediction algorithms. A total of 14,005 genes were detected in total fraction. A total of 104 genes were differentially regulated (73 upregulated and 31 downregulated) in MDD group based on 1.3-fold change threshold and p < 0.05 criteria. In synaptosomes, out of 13,236 detectable genes, 234 were upregulated and 60 were downregulated (>1.3-fold, p < 0.05). Several of these altered genes were validated independently by a quantitative polymerase chain reaction (qPCR). GO revealed an association with immune system processes and cell death. Moreover, a cluster of genes belonged to the nervous system development, and psychological disorders were discovered using gene–gene network analysis. The ratio of synaptic/total fraction showed a shift in expression of 119 genes in MDD subjects, which were primarily associated with neuroinflammation, interleukin signaling, and cell death. Our results suggest not only large-scale gene expression changes in synaptosomes, but also a shift in the expression of genes from total to synaptic fractions of dlPFC of MDD subjects with their potential role in immunomodulation and cell death. Our findings provide new insights into the understanding of transcriptomic regulation at the synapse and their possible role in MDD pathogenesis.

scholarly journals Review of Cognitive Characteristics of Autism Spectrum Disorder Using Performance on Six Subtests on Four Versions of the Wechsler Intelligence Scale for Children

2021 ◽  
Author(s):  
Mizuho Takayanagi ◽  
Yoko Kawasaki ◽  
Mieko Shinomiya ◽  
Hoshino Hiroshi ◽  
Satoshi Okada ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Block Design ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Intelligence Scale ◽  
Cognitive Characteristics ◽  
Children With Asd ◽  
The Right ◽  
The Impact

AbstractThis study was a systematic review of research using the Wechsler Intelligence Scale for Children (WISC) with Autism Spectrum Disorder (ASD) to examine cognitive characteristics of children with ASD beyond the impact of revisions based on WISC and diagnostic criteria changes. The classic “islets of ability” was found in individuals with full-scale IQs < 100. The “right-descending profiles” were observed among high IQ score individuals. High levels on the Block Design and low Coding levels were consistently found regardless of the variation in intellectual functioning or diagnosis. This review identified patterns of cognitive characteristics in ASD individuals using empirical data that researchers may have previously been aware of, based on their experiences, owing to the increased prevalence of ASD.

scholarly journals A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder

2021 ◽  
Vol 11 (6) ◽  
pp. 488
Author(s):  
Daniel A Rossignol ◽  
Richard E Frye
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Immunoglobulin G ◽  
Meta Analysis ◽  
Intravenous Immunoglobulins ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Effect Sizes ◽  
Aberrant Behavior ◽  
Children With Asd

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.

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