Factors In Autism Research Articles

Examining a model of anxiety in autistic adults.

Anxiety disorders commonly occur in autism. Existing studies implicate intolerance of uncertainty, alexithymia, sensory processing differences and emotion regulation difficulties as influencing factors of anxiety in autism. To date, a few studies have considered the combination of these factors within the same sample. This study used structural equation modelling to test the prediction that intolerance of uncertainty and emotion regulation constitute more direct causes of anxiety in autism that mediate the influences of sensory processing difference and alexithymia as more sequential contributing factors. Autistic (n = 86) and non-autistic adults (n = 100) completed a battery of self-report questionnaires. Only when applied to each group separately, the broad predictions of the model were confirmed for the autistic group following data-driven additions of paths between sensory processing difference and anxiety and alexithymia implying that sensory processing difference contribute indirectly as well as directly to individual differences in anxiety. For the non-autistic group, model fit could only be achieved after removing autism-related traits and sensory processing differences as predictors of anxiety. These results suggest that aetiology and expression of anxiety in autism partially overlap with what is observed in the general population except that sensory processing differences appear to play a relatively unique role in the context of autism.

Interactions between the lipidome and genetic and environmental factors in autism

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.

Linking Sensory Integration and Processing With Mental Health in Autism: A Retrospective Review of Survey Data.

Although a central tenet of occupational therapy practice, evidence-based practice is at times overrepresented by research and can overlook the contributions of clinical expertise, the lived experience, and context. This survey affords the occupational therapy practitioner the opportunity to understand sensory integration and processing (SI/P) as experienced by autistic adults. To explore the following research question through a retrospective analysis of an internet-based survey: What is the relationship between the SI/P differences and mental health concerns reported by autistic adults? Nonexperimental; retrospective analysis of data collected from September 2018 through June 2019. The analysis team joined the project after the survey had been launched. The Grand Sensory Survey (GSS) was available internationally through the websites and social media accounts of the Autistic Empire and STAR Institute for Sensory Processing. The sample included 440 total responses. Excluding responses from participants ages ≤18 yr (n = 24), 416 responses were included: n = 189 identified as autistic, n = 147 identified as nonautistic, and n = 80 did not provide a response to this query. The GSS included questions about demographics, mental health, and sensory experiences. Both SI/P disruptions and sensory sensitivity predicted anxiety and depression (p < .001). Differences in SI/P are significant factors in mental health for autistic adults. What This Article Adds: We implicate multiple aspects of SI/P and their influence on mental health among autistic adults. The autistic-led design of the survey ensures representation of issues that are pivotal to the autistic community, broadening the template for aspects of SI/P that should be considered when looking at client factors in autism and influence on function and participation. Positionality Statement: The authors deliberately use identity first language in keeping with requests from the autistic community (see https://autisticadvocacy.org/about-asan/identity-first-language/). This language is favored by autistic communities and self-advocates and has been adopted by health care professionals and researchers (Bottema-Beutel etal., 2021; Kenny etal., 2016). This article is written from the perspective of the social model of disability and a neurodiversity affirming frame of reference. Three of the five authors are autistic.

Autism, Primitive Rebellion Against Authoritarian Theocratism – Family Education, Alpha Emitting Nanoparticulates and Bigotries

While it has been shown earlier that alpha emitters are a founding factor in autism, there is another factor related to societal organization, with parental control on children inspired by authoritarian religions being a major complementary element in the emergence of the disease. Catholic principles in particular appear extremely related to it, and this can be demonstrated in many ways. In general, the abnormality of the familial order creates reactions in children, which reintroduce some of the naturality forgotten, as fine (toll) for their parents. All authoritarian theocratic societal organizations create issues in family education that spill into autism in children as protective reaction.

Conserved and Distinct Functions of the Autism-Related Chromatin Remodeler CHD8 in Embryonic and Adult Forebrain Neurogenesis.

The chromatin remodeler CHD8 represents a high-confidence risk factor in autism, a multistage progressive neurologic disorder, however the underlying stage-specific functions remain elusive. In this study, by analyzing Chd8 conditional knock-out mice (male and female), we find that CHD8 controls cortical neural stem/progenitor cell (NSC) proliferation and survival in a stage-dependent manner. Strikingly, inducible genetic deletion reveals that CHD8 is required for the production and fitness of transit-amplifying intermediate progenitors (IPCs) essential for upper-layer neuron expansion in the embryonic cortex. p53 loss of function partially rescues apoptosis and neurogenesis defects in the Chd8-deficient brain. Further, transcriptomic and epigenomic profiling indicates that CHD8 regulates the chromatin accessibility landscape to activate neurogenesis-promoting factors including TBR2, a key regulator of IPC neurogenesis, while repressing DNA damage- and p53-induced apoptotic programs. In the adult brain, CHD8 depletion impairs forebrain neurogenesis by impeding IPC differentiation from NSCs in both subventricular and subgranular zones; however, unlike in embryos, it does not affect NSC proliferation and survival. Treatment with an antidepressant approved by the Federal Drug Administration (FDA), fluoxetine, partially restores adult hippocampal neurogenesis in Chd8-ablated mice. Together, our multistage functional studies identify temporally specific roles for CHD8 in developmental and adult neurogenesis, pointing to a potential strategy to enhance neurogenesis in the CHD8-deficient brain.SIGNIFICANCE STATEMENT The role of the high-confidence autism gene CHD8 in neurogenesis remains incompletely understood. Here, we identify a stage-specific function of CHD8 in development of NSCs in developing and adult brains by conserved, yet spatiotemporally distinct, mechanisms. In embryonic cortex, CHD8 is critical for the proliferation, survival, and differentiation of both NSC and IPCs during cortical neurogenesis. In adult brain, CHD8 is required for IPC generation but not the proliferation and survival of adult NSCs. Treatment with FDA-approved antidepressant fluoxetine partially rescues the adult neurogenesis defects in CHD8 mutants. Thus, our findings help resolve CHD8 functions throughout life during embryonic and adult neurogenesis and point to a potential avenue to promote neurogenesis in CHD8 deficiency.

Is the MTHFR C677T variant a genetic risk factor in the etiology of autism spectrum disorder? Is it alone or by combined with rare variants of the PHGDH gene? Running Title: Is the MTHFR C677T a genetic risk factor for autism?

Is the MTHFR C677T variant a genetic risk factor in the etiology of autism spectrum disorder? Is it alone or by combined with rare variants of the PHGDH gene? Running Title: Is the MTHFR C677T a genetic risk factor for autism?

Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India.

Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population. Aim The present study hypothesized that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [ NLGN4Y ] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India. Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid. Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [ NLGN4Y ] gene especially in the male predominance of autism in Indian autistic population.

Alternations in the Cardiovascular Autonomic Regulation and Growth Factors in Autism.

Autism spectrum disorder (ASD) represents a serious neurodevelopmental disorder associated with autonomic nervous system dysregulation. The aim was to study complex cardiovascular autonomic regulation using heart rate variability (HRV) and systolic blood pressure variability (SBPV) linear/non-linear analysis at rest and during orthostasis, and to assess plasma levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in autistic children. Twenty-five ASD boys and 25 age and gender-matched children at the age 7-15 years were examined. After venous blood taking, continuous ECG and blood pressure biosignals were recorded at rest and during orthostasis. Evaluated parameters: RR intervals, high- and low-frequency band of HRV spectral analysis (HF-HRV, LF-HRV), symbolic dynamics parameters 0V%, 1V%, 2LV%, 2UV%, low- and high-frequency band of SBPV (LF-SBPV, HF-SBPV), systolic, diastolic, mean blood pressure, EGF, VEGF plasma levels. RR intervals were significantly shortened and the HF-HRV, LF-SBPV, HF-SBPV parameters were significantly lower at rest, the HF-HRV and LF-SBPV remained lower during orthostasis in autistic children compared to controls (p<0.05). EGF plasma levels were significantly lower in ASD compared to controls (p=0.046). No significant differences were found in remaining parameters. Our study revealed tachycardia, cardiovagal underactivity, and blunted sympathetic vasomotor regulation at rest and during orthostasis in autistic children. Additionally, complex heart rate dynamics are similar in autistic children than controls. Furthermore, EGF was reduced in autistic children without significant correlations with any autonomic parameters. We suggest that the abnormal complex cardiovascular reflex control could contribute to understanding the pathway linking autonomic features and autism.

A systematic review of romantic relationship initiation and maintenance factors in autism

AbstractAutistic individuals report similar levels of interest in romantic relationships to their nonautistic peers but experience greater challenges with the initiation and maintenance of these relationships. This systematic review synthesizes the factors that contribute to romantic relationship initiation and maintenance among autistic individuals to inform relationship support programs. Both successes (e.g., ability to initiate relationships and maintain a satisfying relationship) and challenges (e.g., relationship dissatisfaction) were investigated. Out of 1403 potentially relevant articles, 11 articles comprising 13 studies met the inclusion criteria (investigated factor[s] of romantic relationship success of challenges, involved participants with a formal autism diagnosis and/or their partners, presented quantitative results in relationship factors, and was available in an English‐language version). Social and communication challenges were studied to the greatest extent and were associated with difficulties in both relationship initiation and satisfaction. Several factors relating to the partner of the autistic individual were associated with successful relationships, including reciprocal liking, partner support, and the ability to meet the autistic partner's needs. Conclusions are limited by the small number of studies but provide initial indications that social and communicative factors, as well as the role of nonautistic partners, are important to the success of romantic relationships for autistic individuals. In keeping in line with the community's preference for identity‐first language (i.e., “autistic individual” rather than “individual with autism”), this language has been used throughout this review.

Diagnosis and Therapy of an Autistic Child

Knowledge of autism is growing tremendously, since the first formulation of the phenomenon of autism in 1943, there is still no cure for the cure of changes in the brain that create the symptoms of autism. I still find better ways of understanding the disease and help patients adapt, but does not give a full understanding of what autism. There are different types of therapy in the field of speech, behavior, vision, hearing, as well as drugs and dietary recommendations, but they are often ineffective. Treatments should be tailored to the individual needs of the patient. The author of that work will pay attention to corrective therapy movement, and the mechanism of imitation, these two factors in autism do not exhibit synchronization, because the child did not received during the birth. Autistic children from the area have movement disorders, and the lack of a mechanism to follow. My research results confirm the view that the movement disorder and the mechanism of imitation are inherent in the phenomenon of autism. The study of movement disorders in children, and the mechanism of imitation, may serve as an early indicator of autism diagnosis methods. They point to the need for the development of therapies to be used from the first months of life in autism.

Potential Risk Factors for Autism in Children Requiring Neonatal Intensive Care Unit.

The etiology of autism spectrum disorder (ASD) is complex and involves the interplay of genetic and environmental factors. We sought to identify potential prenatal, perinatal, and neonatal risk factors for ASD in a unique population of children who had perinatal complications and required care in a neonatal intensive care unit (NICU). This prospective cohort study included 73 patients discharged from a NICU who received long-term follow-up at the largest children's hospital in Brazil. Potential risk factors were compared between 44 children with a diagnosis of ASD and 29 children without using the Mann-Whitney U test. Proportions were analyzed using the chi-square test. Simple and multiple logistic regression tests were performed. Of 38 factors analyzed, the following 7 were associated with ASD: family history of neuropsychiatric disorders (p = 0.049); maternal psychological distress during pregnancy (p = 0.007); ≥ 26 days in the NICU (p = 0.001); feeding tube for ≥ 15 days (p = 0.014); retinopathy of prematurity (p = 0.022); use of three or more antibiotics (p = 0.008); and co-sleeping until up to 2 years of age (p = 0.004). This study found associations between specific risk factors during critical neurodevelopmental periods and a subsequent diagnosis of ASD. Knowledge of the etiologic factors that may influence the development for ASD is paramount for the development of intervention strategies and improvement of prognoses.

Towards robust and replicable sex differences in the intrinsic brain function of autism

BackgroundMarked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.MethodsWe addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7–18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research.ResultsDiscovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples—EU-AIMS LEAP.LimitationsGiven the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.ConclusionsAtypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.

31.B. Workshop: Public health and urban design: an interdisciplinary approach to promote autism friendly environments

Abstract Autism is a set of heterogeneous neurodevelopmental conditions, characterised by early-onset difficulties in social communication and restricted, repetitive behaviour and interests. The worldwide population prevalence is about 1% with an increasing incidence and prevalence rates. Autism affects more male than female individuals, and comorbidity is common (&amp;gt;70% have concurrent conditions). Determinants of these changes in incidence and prevalence rates may also be related to exposure to environmental factors and to modifications in diagnostic concepts and criteria. In spite of the uncertainty in determinants of incidence of autisms, there is evidence that environmental characteristics play a significant role both as autism risk factors and as potential obstacles that influence the capabilities of autonomously and fully “using” everyday spaces. The workshop aims to provide a framework on risk factors of autism and explore the relationship with the built environment, focusing on the quality of the everyday spaces and projecting the effects that it could have in the long term on achieving a desirable level of quality of life. The 11th Sustainable Development Goals of United Nations “Make cities inclusive, safe, resilient and sustainable” underlines the necessity of designing policies and projects acting to enhance and promote healthy cities and communities by addressing the needs of the most vulnerable groups of inhabitants. Herewith we bring together the discipline of Public Health and Urban Design to promote an interdisciplinary debate on a little explored topic investigating how the approaches adopted during childhood to promote the wellbeing of people with ASD can be related or strengthen by focusing also on built environment design intervention to pursue and reach the same objectives even during adulthood. The workshop will consist of four presentations. The first focuses on giving an overview on current knowledge of intervention for people with autism, presenting also criteria for evidence-based interventions. The second explores the relationship between autism and built environment by providing an exhaustive framework of the available research literature in order to identify a first set of spatial requirements for autism friendly cities. The third examines the impact of built environment on ASD users with the aim of developing a specific evaluation tool for healthcare spaces and best practices formulation according to the specific sensorial hypo- or hyper-activation of people with autism. Finally, the fourth reports the results of a two years Research &amp; Development project called “GAP REDUCE” finalized at developing an Assistive Technology tool to support people with ASD, adult and high-functioning, to plan urban itineraries towards daily destinations. Key messages World's incidence of autism is about 1% with an increasing incidence whose determining rates may also be related to environmental factors and to modifications in diagnostic concepts and criteria. Environmental characteristics play a significant role also as potential obstacles that influence the capabilities of people with autism of autonomously and fully “using” everyday spaces.

Should autism spectrum disorder be considered part of CHARGE syndrome? A cross-sectional study of 46 patients

BackgroundBehavioral problems are an important issue for people with CHARGE syndrome. The similarity of their behavioral traits with those of people with autism raises questions. In a large national cross-sectional study, we used specific standardized tools for diagnosing autism (Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders, 5th edition, DSM-5) and evaluating behavioral disorders (Developmental Behavior Checklist-Parents, DBC-P) to investigate a series of individuals with CHARGE syndrome, defined by Verloes’s criteria. We evaluated their adaptive functioning level and sensory particularities and extracted several data items from medical files to assess as potential risk factors for autism and/or behavioral disorders.ResultsWe investigated 64 individuals with CHARGE syndrome (35 females; mean age 10.7 years, SD 7.1 years). Among 46 participants with complete results for the Autism Diagnostic Interview-Revised (ADI-R), 13 (28%) had a diagnosis of autism according to the ADI-R, and 25 (54%) had a diagnosis of autism spectrum disorder (ASD) according to the DSM-5 criteria. The frequency of autistic traits in the entire group was a continuum. We did not identify any risk factor for ASD but found a negative correlation between the ADI-R score and adaptive functioning level. Among 48 participants with data for the DBC-P, 26 (55%) had behavioral disorders, which were more frequent in patients with radiological brain anomalies, impaired adaptive functioning, later independent walking, and more sensory particularities.ConclusionsASD should be considered to be an independent risk requiring early screening and management in children born with CHARGE syndrome.

Fetal exposure to air pollution as a potential risk factor for autism and ADHD

Fetal exposure to air pollution as a potential risk factor for autism and ADHD

Sulfate Deficiency as a Risk Factor for Autism

This is a study of water and beverages consumed during pregnancy by mothers of children with autism. Materials included vials for water samples and a survey to describe the water and beverages. Samples were tested for sulfate and surveys evaluated for average daily levels. Results were stratified for selected regions of the United States. Areas with the highest rates of autism showed a trend toward lower levels of sulfate compared to areas with low rates of autism (28% sulfate, n = 45, p = 0.059). Severe autism was associated with low sulfate levels while mild symptoms were associated with higher levels of sulfate (− 0.32 correlation, n = 86, p < 0.01). The results suggest that sulfate may be helpful in reducing both the incidence and severity of autism.

Deletion of Semaphorin 3F in Interneurons Is Associated with Decreased GABAergic Neurons, Autism-like Behavior, and Increased Oxidative Stress Cascades

Autism and epilepsy are diseases which have complex genetic inheritance. Genome-wide association and other genetic studies have implicated at least 500+ genes associated with the occurrence of autism spectrum disorders (ASD) including the human semaphorin 3F (Sema 3F) and neuropilin 2 (NRP2) genes. However, the genetic basis of the comorbid occurrence of autism and epilepsy is unknown. The aberrant development of GABAergic circuitry is a possible risk factor in autism and epilepsy. Molecular biological approaches were used to test the hypothesis that cell-specific genetic variation in mouse homologs affects the formation and function of GABAergic circuitry. The empirical analysis with mice homozygous null for one of these genes, Sema 3F, in GABAergic neurons substantiated these predictions. Notably, deletion of Sema 3F in interneurons but not excitatory neurons during early development decreased the number of interneurons/neurites and mRNAs for cell-specific GABAergic markers and increased epileptogenesis and autistic behaviors. Studies of interneuron cell-specific knockout of Sema 3F signaling suggest that deficient Sema 3F signaling may lead to neuroinflammation and oxidative stress. Further studies of mouse KO models of ASD genes such as Sema 3F or NRP2 may be informative to clinical phenotypes contributing to the pathogenesis in autism and epilepsy patients.

Is the Use of Cannabis During Pregnancy a Risk Factor for Autism?

The use of marijuana by healthy adults is commonly viewed as having limited adverse health effects; however, its potential risks for fetal developmental abnormalities when used during pregnancy have not been thoroughly evaluated. It is, therefore, important that the effects of prenatal marijuana on the developing fetus be fully assessed in order to create a proper set of guidelines for use before, during and after pregnancy as is standard with other drugs such as alcohol and nicotine.

Bumper scan of genomes pinpoints inherited risk factors for autism

Bumper scan of genomes pinpoints inherited risk factors for autism

Is Prenatal Valproate Exposure a Risk Factor for Autism

Sodium valproate (Depakene) and divalproex sodium (Depakote) are two commonly used drugs for epilepsy therapy. Sodium valproate, a first-generation antiepileptic drug, has commonly been used as a treatment for different forms of both epilepsy and psychiatric disorders ever since it was first clinically utilized in 1967. It is a simple 2-chain fatty acid that is believed to affect GABA metabolism, however, the mechanism is still unclear. It has been proven to have adverse side effects, such as neural tube defects if taken in utero during the first trimester of pregnancy and has therefore caused a reservation in the medical community for prescription of this drug in females. However, it is still one of the most commonly prescribed agents in young women of childbearing age with 23.4% of women actively receiving it for non-epileptic disorders, such as psychiatric disorders and 12% of women receiving it as an antiepileptic drug (AED). This may be cause for alarm due to the teratogenic effects that may result from usage of valproate. In this article, the potential of prenatal valproate to cause autism spectrum disorder will be outlined from a nonclinical and clinical perspective, as evident from this basic science report. Overall, valproate is clearly associated with teratogenic risks and hence should not be used in women with epilepsy during reproductive years.