The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.
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ABSTRACT:
SUBMITTER: Masi A
PROVIDER: S-EPMC5360854 | biostudies-other | 2017 Apr
REPOSITORIES: biostudies-other
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Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.
2020-05-03 | GSE89596 | GEO
Project description:Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in ~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.
| S-EPMC5143489 | biostudies-literature
Project description:BackgroundEarly identification and treatment of individuals with autism spectrum disorder (ASD) improves outcomes, but specific evidence needed to individualize treatment recommendations is lacking. Biomarkers that could be routinely measured within the clinical setting could potentially transform clinical care for patients with ASD. This demonstration project employed collection of biomarker data during regular autism specialty clinical visits and explored the relationship of biomarkers with clinical ASD symptoms.MethodsEighty-three children with ASD, aged 5-10 years, completed a multi-site feasibility study integrating the collection of biochemical (blood serotonin, urine melatonin sulfate excretion) and clinical (head circumference, dysmorphology exam, digit ratio, cognitive and behavioral function) biomarkers during routine ASD clinic visits. Parents completed a demographic survey and the Aberrant Behavior Checklist-Community. Cognitive function was determined by record review. Data analysis utilized Wilcoxon two-sample tests and Spearman correlations.ResultsParticipants were 82% male, 63% White, 19% Hispanic, with a broad range of functioning. Group means indicated hyperserotonemia. In a single regression analysis adjusting for race and median household income, higher income was associated with higher levels of blood serotonin and urine melatonin sulfate excretion levels (p = 0.004 and p = 0.04, respectively). Melatonin correlated negatively with age (p = 0.048) and reported neurologic problems (p = 0.02). Dysmorphic status correlated with higher reported stereotyped behavior (p = 0.02) and inappropriate speech (p = 0.04).ConclusionThis demonstration project employed collection of multiple biomarkers, allowed for examination of associations between biochemical and clinical measures, and identified several findings that suggest direction for future studies. This clinical research model has promise for integrative biomarker research in individuals with complex, heterogeneous neurodevelopmental disorders such as ASD.
| S-EPMC6687766 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is a behaviorally defined and heterogeneous disorder. Biomarkers for ASD offer the opportunity to improve prediction, diagnosis, stratification by severity and subtype, monitoring over time and in response to interventions, and overall understanding of the underlying biology of this disorder. A variety of potential biomarkers, from the level of genes and proteins to network-level interactions, is currently being examined. Many of these biomarkers relate to inhibition, which is of particular interest because in many cases ASD is thought to be a disorder of imbalance between excitation and inhibition. Abnormalities in inhibition at the cellular level lead to emergent properties in networks of neurons. These properties take into account a more complete genetic and cellular background than findings at the level of individual genes or cells, and are able to be measured in live humans, offering additional potential as diagnostic biomarkers and predictors of behaviors. In this review we provide examples of how altered inhibition may inform the search for ASD biomarkers at multiple levels, from genes to cells to networks.
| S-EPMC4489951 | biostudies-literature
Project description:Autism Spectrum Disorder (ASD) lacks validated measures of core social functions across development stages suitable for clinical trials. We assessed the concurrent validity between ASD clinical measures and putative biomarkers of core deficits, and their feasibility of implementation in human studies. Datasets from two adult ASD studies were combined (observational study [n = 19] and interventional study baseline data [n = 19]). Potential biomarkers included eye-tracking, olfaction, and auditory and visual emotion recognition assessed via the Affective Speech Recognition test (ASR) and Reading-the-Mind-in-the-Eyes Test (RMET). Current functioning was assessed with intelligence quotient (IQ), adaptive skill testing, and behavioral ratings. Autism severity was determined by the Autism Diagnostic Observation Scale-2 and Social Communication Interaction Test (SCIT). Exploratory measures showed varying significant associations across ASD severity, adaptive skills, and behavior. Eye tracking endpoints showed little relationship to adaptive ability but correlated with severity and behavior. ASR scores significantly correlated with most adaptive behavior domains, as well as severity. Olfaction predicted visual and auditory emotion recognition. SCIT scores related moderately to multiple severity domains, and was the only measure not related with IQ. RMET accuracy was less related to ASD features. Eye tracking, SCIT, and ASR showed high test-retest reliability. We documented associations of proximal biomarkers of social functioning with multiple ASD dimensions. With the exception of SCIT, most correlations were modest, limiting utility as proxy measures of social communication. Feasibility and reliability were high for eye-tracking, ASR, and SCIT. Overall, several novel experimental paradigms showed potential as social biomarkers or surrogate markers in ASD. Autism Research 2018, 11: 1567-1579. © 2018 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: More accurate measurements of treatment effects are needed to help the development of new drug treatments for autism spectrum disorders (ASD). This study evaluates the relationship between assessments designed to measure behaviors associated with social communication and cognition in ASD with clinical and diagnostic assessments of symptom severity as well as their implementation. The assessments including eye-tracking, auditory and visual social stimuli recognition, and olfaction identification showed potential for use in the evaluation of treatments for social difficulties in ASD.
| S-EPMC6282609 | biostudies-literature
Project description:Autism spectrum disorder (ASD) affects approximately 2% of children in the United States (US) yet its etiology is unclear and effective treatments are lacking. Therapeutic interventions are most effective if started early in life, yet diagnosis often remains delayed, partly because the diagnosis of ASD is based on identifying abnormal behaviors that may not emerge until the disorder is well established. Biomarkers that identify children at risk during the pre-symptomatic period, assist with early diagnosis, confirm behavioral observations, stratify patients into subgroups, and predict therapeutic response would be a great advance. Here we underwent a systematic review of the literature on ASD to identify promising biomarkers and rated the biomarkers in regards to a Level of Evidence and Grade of Recommendation using the Oxford Centre for Evidence-Based Medicine scale. Biomarkers identified by our review included physiological biomarkers that identify neuroimmune and metabolic abnormalities, neurological biomarkers including abnormalities in brain structure, function and neurophysiology, subtle behavioral biomarkers including atypical development of visual attention, genetic biomarkers and gastrointestinal biomarkers. Biomarkers of ASD may be found prior to birth and after diagnosis and some may predict response to specific treatments. Many promising biomarkers have been developed for ASD. However, many biomarkers are preliminary and need to be validated and their role in the diagnosis and treatment of ASD needs to be defined. It is likely that biomarkers will need to be combined to be effective to identify ASD early and guide treatment.
| S-EPMC6989979 | biostudies-literature
Project description:Autism spectrum disorder (ASD) refers to a heterogeneous group of complex neurodevelopmental disorders characterized by social skill and communication deficits, along with stereotyped repetitive behavior. miRNAs, small non-coding RNAs that have been recognized as critical regulators of gene expression, play a key role in the neurodevelopmental transcriptional networks of the human brain. Previous investigations have proven that circulating miRNAs open up new possibilities for the emerging roles of diagnostic and prognostic biomarkers in human disorders and diseases. Biomarker development has been progressively becoming more recognized as a cornerstone in medical diagnosis, paving the way to drug discoveries and limiting the progression of various diseases. Due to the complexity of ASD, considerable endeavors have either unsuccessfully identified biomarkers for the disorder or have not yet been established. Cell-free circulating miRNAs in biofluids are extraordinarily stable and considered to represent the next-generation of clinical, non-invasive, biomarkers for many pathologies including neurological and neurodevelopmental disorders. Here, we conducted a review of all peer-reviewed articles addressing the circulating profiles of miRNAs, mostly performed in serum and saliva samples in individuals with ASD.
| S-EPMC6808050 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-02-27 | GSE111176 | GEO
Project description:The aim of this study was to identify ASD vulnerability components, explore possible vulnerability subgroups, and evaluate environmental contribution to phenotypic variability. We performed PCA and cluster analysis using ASD risk factor data. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 a higher correlation with biological factors (Psychiatric Family History and Gestational Complications). Clustering analysis of PCA scores using bootstrap approach showed two clusters. Comparing the methylome between clusters we found 11.879 DMPs (p<0.05), and their CpG sites were enriched in VMRs, most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability score moderated by epigenetic clock was associated with Vineland Total score (p=0.0036, adjR2=0.31), suggesting risk factors with stress burden can influence phenotype.
2021-10-01 | GSE164563 | GEO
Project description:Background: Although increasing evidence suggests an association between alterations in peripheral cytokines and autism spectrum disorder (ASD), a consensus is lacking. To determine whether abnormal cytokine profiles in peripheral blood were associated with ASD, we performed this systemic review and meta-analysis. Methods: A systematic literature search was conducted through the Embase, PubMed, Web of Knowledge, PsycINFO, and Cochrane databases up to 4 June 2020. Clinical studies exploring the aberration of peripheral cytokines of autistic patients and controls were included in our meta-analysis. We pooled extracted data using fixed- or random-effects models based on heterogeneity tests with Comprehensive Meta-analysis software. We converted standardized mean differences to Hedges' g statistic to obtain the effect sizes adjusted for sample size. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also carried out. Results: Sixty-one articles (326 studies) were included to assess the association between 76 cytokines and ASD. We conducted our meta-analysis based on 37 cytokines with 289 studies. Since there were fewer than three studies on any of the other 39 cytokines, we only provided basic information for them. The levels of peripheral IL-6, IL-1β, IL-12p70, macrophage migration inhibitory factor (MIF), eotaxin-1, monocyte chemotactic protein-1 (MCP-1), IL-8, IL-7, IL-2, IL-12, tumor necrosis factor-α (TNF-α), IL-17, and IL-4 were defined as abnormal cytokines in the peripheral blood of ASD patients compared with controls. The other 24 cytokines did not obviously change in ASD patients compared with the controls. Conclusions: The findings of our meta-analysis strengthen the evidence for an abnormal cytokine profile in ASD. These abnormal cytokines may be potential biomarkers for the diagnosis and treatment of ASD in the future.
| S-EPMC8283413 | biostudies-literature