Autism Overview

This overviews Autism, including causes, evaluation Strategies, genetic counseling, management and further resources.GeneReviews is funded by the National Institutes of Health and Developed at the University of Seattle, Washington

Nitric oxide donation lowers blood pressure in adrenocorticotrophic hormone-induced hypertensive rats.

Adrenocorticotrophic hormone (ACTH) elevates systolic blood pressure (SBP) and lowers plasma reactive nitrogen intermediates in rats. We assessed the ability of NO donation from isosorbide dinitrate (ISDN) to prevent or reverse the hypertension caused by ACTH. In the prevention study, male Sprague Dawley rats were treated with ACTH (0.2 mg/kg/day) or saline control for 8 days, with either concurrent ISDN (100 mg/kg/day) via the drinking water or water alone. Animals receiving ISDN via the drinking water were provided with nitrate-free water for 8 hours every day. In the reversal study ISDN (100 mg/kg) or vehicle was given as a single oral dose on day 8. SBP was measured daily by the indirect tail-cuff method in conscious, restrained rats. ACTH caused a significant increase in SBP compared with saline (P < 0.0015). In the prevention study, chronic administration of ISDN (100 mg/kg/day) did not affect the SBP in either group. In the reversal study, ISDN significantly lowered SBP in ACTH-treated rats at 1 and 2.5 hours (132 +/- 3 mmHg (1 h) and 131 +/- 2 mmHg (2.5 h) versus 143 +/- 3 mmHg (0 h), P < 0.002), but not to control levels. It had no effect in control (saline treated) rats. In conclusion, the lowering of SBP by NO donation is consistent with the notion that ACTH-induced hypertension involves an impaired bioavailability or action of NO in vivo

Medical genetics : impact and strategy : (genetic disease, birth defects, prenatal diagnosis)

Genetic diseases and birth defects have a major impact on all levels of health care because of their enormous consequences for the individual and family and because of the high frequency of occurrence. That over 3000 described disorders due to either chromosome aberrations, to single-gene mutations or to many genes acting together and with the environment have been described illustrates the diversity in these diseases. The concern of the medical geneticist is to establish an accurate etiologic diagnosis, to counsel patients and families concerning their risks of occurrence or recurrence and to devise and provide methods of preventing both the effects and ultimately the occurrence of genetic diseases.JUDITH H. MILES, Department of Child Health, University of Missouri Health Sciences Center, Columbia, Missouri

Facial phenotypes in subgroups of prepubertal boys with autism spectrum disorders are correlated with clinical phenotypes

<p>Abstract</p> <p>Background</p> <p>The brain develops in concert and in coordination with the developing facial tissues, with each influencing the development of the other and sharing genetic signaling pathways. Autism spectrum disorders (ASDs) result from alterations in the embryological brain, suggesting that the development of the faces of children with ASD may result in subtle facial differences compared to typically developing children. In this study, we tested two hypotheses. First, we asked whether children with ASD display a subtle but distinct facial phenotype compared to typically developing children. Second, we sought to determine whether there are subgroups of facial phenotypes within the population of children with ASD that denote biologically discrete subgroups.</p> <p>Methods</p> <p>The 3dMD cranial System was used to acquire three-dimensional stereophotogrammetric images for our study sample of 8- to 12-year-old boys diagnosed with essential ASD (<it>n </it>= 65) and typically developing boys (<it>n </it>= 41) following approved Institutional Review Board protocols. Three-dimensional coordinates were recorded for 17 facial anthropometric landmarks using the 3dMD Patient software. Statistical comparisons of facial phenotypes were completed using Euclidean Distance Matrix Analysis and Principal Coordinates Analysis. Data representing clinical and behavioral traits were statistically compared among groups by using χ²tests, Fisher's exact tests, Kolmogorov-Smirnov tests and Student's <it>t</it>-tests where appropriate.</p> <p>Results</p> <p>First, we found that there are significant differences in facial morphology in boys with ASD compared to typically developing boys. Second, we also found two subgroups of boys with ASD with facial morphology that differed from the majority of the boys with ASD and the typically developing boys. Furthermore, membership in each of these distinct subgroups was correlated with particular clinical and behavioral traits.</p> <p>Conclusions</p> <p>Boys with ASD display a facial phenotype distinct from that of typically developing boys, which may reflect alterations in the prenatal development of the brain. Subgroups of boys with ASD defined by distinct facial morphologies correlated with clinical and behavioral traits, suggesting potentially different etiologies and genetic differences compared to the larger group of boys with ASD. Further investigations into genes involved in neurodevelopment and craniofacial development of these subgroups will help to elucidate the causes and significance of these subtle facial differences.</p

Home garden use during COVID-19:Associations with physical and mental wellbeing in older adults

The COVID-19 pandemic has affected many aspects of people's lives. Lockdown measures to reduce the spread of COVID-19 have been more stringent for those aged over 70, at highest risk for the disease. Here, we examine whether home garden usage is associated with self-reported mental and physical wellbeing in older adults, during COVID-19 lockdown in Scotland. This study analysed data from 171 individuals (mean age 84 ± 0.5 years) from the Lothian Birth Cohort 1936 study who completed an online survey approximately two months after lockdown commenced (May/June, 2020), and reported having access to a home garden. The survey also included items on garden activities (gardening, relaxing), frequency of garden usage during lockdown, and measures of self-rated physical health, emotional and mental health, anxiety about COVID-19, and sleep quality. Ordinal regression models were adjusted for sex, living alone, education, occupational social class, anxiety and depressive symptoms, body mass index, and history of diabetes and cardiovascular disease. Neither gardening nor relaxing in the garden were associated with health outcomes. However, higher frequency of garden usage during lockdown was associated with better self-rated physical health (P = 0.005), emotional and mental health (P = 0.04), sleep quality (P = 0.03), and a composite health score (P = 0.001), after adjusting for covariates. None of the garden measures were associated with perceived change in physical health, mental and emotional health, or sleep quality, from pre-lockdown levels. The results of the current study provide support for positive health benefits of spending time in a garden—though associations may be bidirectional—and suggest that domestic gardens could be a potential health resource during the COVID-19 pandemic

Facial Structure Analysis Separates Autism Spectrum Disorders Into Meaningful Clinical Subgroups

Varied cluster analysis were applied to facial surface measurements from 62 prepubertal boys with essential autism to determine whether facial morphology constitutes viable biomarker for delineation of discrete Autism Spectrum Disorders (ASD) subgroups. Earlier study indicated utility of facial morphology for autism subgrouping (Aldridge et al. in Mol Autism 2(1):15, 2011). Geodesic distances between standardized facial landmarks were measured from three-dimensional stereo-photogrammetric images. Subjects were evaluated for autism-related symptoms, neurologic, cognitive, familial, and phenotypic variants. The most compact cluster is clinically characterized by severe ASD, significant cognitive impairment and language regression. This verifies utility of facially-based ASD subtypes and validates Aldridge et al.\u27s severe ASD subgroup, notwithstanding different techniques. It suggests that language regression may define a unique ASD subgroup with potential etiologic differences

Detecting Thalamic Abnormalities in Autism Using Cylinder Conformal Mapping

Abstract. A number of studies have documented that autism has a neurobiological basis, but the anatomical extent of these neurobiological abnormalities is largely unknown. In this paper, we applied advanced computational techniques to extract 3D surface models of the thalamus and subsequently analyze highly localized shape variations in a homogeneous group of autism children. In particular, a new conformal parameterization for high genus surfaces is applied in our shape analysis work, which maps the surfaces onto a cylinder domain. Surface matching among different individual meshes is achieved by re-triangulating each mesh according to the template. Children with autism and their controls are compared, and statistical significant abnormalities in thalamus of autism are detected

Enabling Polyvocality in Interactive Documentaries through ‘Structural Participation’

Recent innovations in online, social and interactive media have led to the emergence of new forms of documentary, such as interactive documentaries (‘i-Docs’), with qualities that lend themselves to more open and inclusive production structures. Still, little is known about the experience of making and/or participating-in these kinds of documentary. Our two-year in-the-wild study engaged a large community-of-interest in the production of an i-Doc to explore the ethically-desirable yet challenging aim of enabling multiple subjects to have agency and control over their representation in a documentary. Our study reveals insights into the experiences of participating in an i-Doc and highlights key sociotechnical challenges. We argue that new sociotechnical infrastructure is needed, that frames both ‘executory’ and ‘structural’ forms of participation as symbiotic elements of a co-design process

CHD8 Regulates Neurodevelopmental Pathways Associated with Autism Spectrum Disorder in Neural Progenitors

Truncating mutations of chromodomain helicase DNA-binding protein 8 (CHD8), and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA sequencing) with genome-wide CHD8 binding (ChIP sequencing). Suppressing CHD8 to levels comparable with the loss of a single allele caused altered expression of 1,756 genes, 64.9% of which were up-regulated. CHD8 showed widespread binding to chromatin, with 7,324 replicated sites that marked 5,658 genes. Integration of these data suggests that a limited array of direct regulatory effects of CHD8 produced a much larger network of secondary expression changes. Genes indirectly down-regulated (i.e., without CHD8-binding sites) reflect pathways involved in brain development, including synapse formation, neuron differentiation, cell adhesion, and axon guidance, whereas CHD8-bound genes are strongly associated with chromatin modification and transcriptional regulation. Genes associated with ASD were strongly enriched among indirectly down-regulated loci (P < 10[superscript −8]) and CHD8-bound genes (P = 0.0043), which align with previously identified coexpression modules during fetal development. We also find an intriguing enrichment of cancer-related gene sets among CHD8-bound genes (P < 10[superscript −10]). In vivo suppression of chd8 in zebrafish produced macrocephaly comparable to that of humans with inactivating mutations. These data indicate that heterozygous disruption of CHD8 precipitates a network of gene-expression changes involved in neurodevelopmental pathways in which many ASD-associated genes may converge on shared mechanisms of pathogenesis.Simons FoundationNancy Lurie Marks Family FoundationNational Institutes of Health (U.S.) (Grant MH095867)National Institutes of Health (U.S.) (Grant MH095088)National Institutes of Health (U.S.) (Grant GM061354)March of Dimes Birth Defects FoundationCharles H. Hood FoundationBrain & Behavior Research FoundationAutism Genetic Resource ExchangeAutism Speaks (Organization)Pitt–Hopkins Research Foundatio