A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder
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ABSTRACT:
SUBMITTER: Seif A
PROVIDER: S-EPMC8591260 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Autism spectrum disorder (autism) is a heterogeneous group of neurodevelopmental conditions characterized by early childhood-onset impairments in communication and social interaction alongside restricted and repetitive behaviors and interests. This review summarizes recent developments in human genetics research in autism, complemented by epigenetic and transcriptomic findings. The clinical heterogeneity of autism is mirrored by a complex genetic architecture involving several types of common and rare variants, ranging from point mutations to large copy number variants, and either inherited or spontaneous (de novo). More than 100 risk genes have been implicated by rare, often de novo, potentially damaging mutations in highly constrained genes. These account for substantial individual risk but a small proportion of the population risk. In contrast, most of the genetic risk is attributable to common inherited variants acting en masse, each individually with small effects. Studies have identified a handful of robustly associated common variants. Different risk genes converge on the same mechanisms, such as gene regulation and synaptic connectivity. These mechanisms are also implicated by genes that are epigenetically and transcriptionally dysregulated in autism. Major challenges to understanding the biological mechanisms include substantial phenotypic heterogeneity, large locus heterogeneity, variable penetrance, and widespread pleiotropy. Considerable increases in sample sizes are needed to better understand the hundreds or thousands of common and rare genetic variants involved. Future research should integrate common and rare variant research, multi-omics data including genomics, epigenomics, and transcriptomics, and refined phenotype assessment with multidimensional and longitudinal measures.
| S-EPMC8477228 | biostudies-literature
Project description:Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click-evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well-characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta-analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically-developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedges's g) for at least one ABR latency component (I, III, V, I-III, III-V, I-V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random-effects regressions to generate component-specific estimates. ASD was associated with longer ABR latencies for Waves III (g?=?0.5, 95% CI 0.1, 0.9), V (g?=?0.7, 95% CI 0.3, 1.1), I-III (g?=?0.7, 95% CI 0.2, 1.2), and I-V (g?=?0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ?8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium-to-large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co-occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018, 11: 916-927. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:Auditory brainstem responses (ABR) may be associated with ASD, but participant characteristics and assessment protocols vary considerably across individual studies. Our goal is to combine the results across these studies to facilitate clarity on the topic. Doing so represents a first step in evaluating whether ABRs yield potential for informing the etiology of ASD risk and/or ASD symptom profiles.
| S-EPMC6026056 | biostudies-literature
Project description:OBJECTIVE:To identify and analyze the scientific evidence of nutritional interventions performed in children and adolescents with Autism Spectrum Disorder. DATA SOURCES:A systematic review was conducted in the MEDLINE, Cochrane Library, Embase, LILACS, Google Scholar, PubMed, PsycINFO and Periódicos CAPES databases, using a search strategy to identify studies published between January 2003 and March 2018, in Portuguese, English and Spanish. Were included studies that described nutritional interventions in children and adolescents with autism spectrum disorders and assessed autistic behavior and/or gastrointestinal symptoms. We excluded other review articles and studies that did not include a control group in the research design. The studies were reviewed for descriptive information, and the quality of evidence was assessed through the GRADE system. DATA SYNTHESIS:18 studies were included in the review, being 16 randomized clinical trials, 1 case-control study and 1 open-label trial. As a result, the implementation of a gluten-free and casein-free diet was the most used intervention among the studies. Of the total, 10 studies showed a positive association of intervention with the evaluated results, while 8 did not find of a significant association. CONCLUSIONS:Although some authors report progress in the symptoms associated with autism in individuals with Autistic Spectrum Disorder undergoing nutritional interventions, there is little scientific evidence to support the use of nutritional supplements or dietary therapies in children and adolescents with autism.
| S-EPMC7077797 | biostudies-literature
Project description: Not available
| S-EPMC10997847 | 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) is defined as a neurodevelopmental condition characterized by social communication impairment, delayed development, social function deficit, and repetitive behaviors. The Center for Disease Control reports an increase in ASD diagnosis rates every year. This systematic review evaluated the use of sulforaphane (SFN) therapy as a potential treatment option for individuals with ASD. PubMed.gov, PubMed Central, Natural Medicines, BoardVitals, Google Scholar and Medline were searched for studies measuring the effects of SFN on behavior and cognitive function. All five clinical trials included in this systematic review showed a significant positive correlation between SFN use and ASD behavior and cognitive function. The current evidence shows with minimal side effects observed, SFN appears to be a safe and effective treatment option for treating ASD.
| S-EPMC7527484 | biostudies-literature
Project description:Posterior superior temporal sulcus (pSTS) is specialized for interpreting perceived human actions, and disruptions to its function occur in autism spectrum disorder (ASD). Here we consider the role of Crus I of neocerebellum in supporting pSTS function. Research has associated Crus I activity with imitation and biological motion perception, and neocerebellum is theorized to coordinate activity among cerebral sites more generally. Moreover, cerebellar abnormalities have been associated with ASD. We hypothesized that disordered Crus I-pSTS interactions could predict social deficits in ASD. 15 high functioning adolescents with ASD and 15 same-age comparison youth participated in an fMRI imitation paradigm; ratings of mentalizing ability were collected via parent report. We predicted that stronger Crus I-pSTS interactions would be associated with better mentalizing ability. Consistent with these hypotheses, stronger psychophysiological interactions between Crus I and right pSTS were associated with greater mentalizing ability among adolescents with ASD. Whole-brain analyses also indicated that typically developing youth recruited right inferior frontal gyrus, left pSTS, medial occipital regions, and precuneus more strongly during imitation than did youth with ASD. Overall, these results indicate that variability in neocerebellar interactions with key cortical social brain sites may help explain individual differences in social perceptual outcomes in ASD.
| S-EPMC6987881 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is very heterogeneous, particularly in language. Studies have suggested that language impairment is linked to auditory-brainstem dysfunction in ASD. However, not all ASD children have these deficits, which suggests potential subtypes of ASD. We classified ASD children into two subtypes according to their speech-evoked auditory brainstem response (speech-ABR) and explored the neural substrates for possible subtypes. Twenty-nine children with ASD and 25 typically developing (TD) peers were enrolled to undergo speech-ABR testing and structural magnetic resonance imaging (sMRI). There were significant differences between the ASD group and TD group in surface area, cortical volume and cortical thickness. According to speech-ABR results, ASD participants were divided into the ASD-typical (ASD-T) group and ASD-atypical (ASD-A) group. Compared with the ASD-T group, the ASD-A group had a lower score in language of the Gesell Developmental Diagnosis Scale (GDDS), increased left rostral middle frontal gyrus (lRMFG) area and decreased local gyrification index of the right superior temporal gyrus. GDDS-language and surface area of lRMFG were correlated to the wave-A amplitude in ASD. Surface area of lRMFG had an indirect effect on language performance via alteration of the wave-V amplitude. Thus, cortical deficits may impair language ability in children with ASD by causing subcortical dysfunction at preschool age. These evidences support dysfunction of the auditory brainstem as a potential subtype of ASD. Besides, this subtype-based method may be useful for various clinical applications.
| S-EPMC8010248 | biostudies-literature
Project description:Clinical guidance documents play an important role in ensuring access to high-quality autism spectrum disorder diagnostic assessment practices. The objective was to perform a systematic review of professional association and government clinical guidance documents for autism spectrum disorder diagnostic assessment, analyzing their quality and content. The government search was limited to English-speaking, single-payer, publicly funded health systems. A quality appraisal was conducted by two appraisers using the Appraisal of Guidelines Research and Evaluation, second edition tool. A content analysis was conducted for recommended clinical personnel and psychometric tools. The 11 documents demonstrated higher quality in Scope and Purpose (mean: 90.1, standard deviation: 7.4) and Clarity of Presentation (mean: 82.8, standard deviation: 9.4) and lower quality in Applicability (mean: 43.3, standard deviation: 23.8) and Rigor of Development (mean: 52, standard deviation: 21.9). All documents either recommended multidisciplinary team assessment or stated it was ideal. The documents varied substantially in their recommended tools and personnel for diagnostic assessment. There was little supporting evidence for team and personnel recommendations. Multiple guidance documents exist for autism spectrum disorder diagnostic assessments, with varying quality and recommendations. The substantial variation likely stems from insufficient evidence supporting assessment practices. Research is required to close the evidence gaps and inform high-quality clinical guidelines.
| S-EPMC6039866 | biostudies-other
Project description:Background:As more animal studies start to disentangle pathways linking the gut microbial ecosystem and neurobehavioral traits, human studies have grown rapidly. Many have since investigated the bidirectional communication between the gastrointestinal tract and the central nervous system, specifically on the effects of microbial composition on the brain and development. Methods:Our review at the initial stage aimed to evaluate literature on gut microbial alterations in pediatric neurobehavioral conditions. We searched five literature databases (Embase, PubMed, PsychInfo, Scopus, and Medline) and found 4489 published work. As the mechanisms linking gut microbiota to these conditions are divergent, the scope of this review was narrowed to focus on describing gut dysbiosis in children with autism spectrum disorder (ASD). Results:Among the final 26 articles, there was a lack of consistency in the reported gut microbiome changes across ASD studies, except for distinguishable patterns, within limits, for Prevotella, Firmicutes at the phylum level, Clostridiales clusters including Clostridium perfringens, and Bifidobacterium species. Conclusions:These results were inadequate to confirm a global microbiome change in children with ASD and causality could not be inferred to explain the etiology of the behaviors associated with ASD. Mechanistic studies are needed to elucidate the specific role of the gut microbiome in the pathogenesis of ASD.
| S-EPMC6996179 | biostudies-literature