Search

Neurodevelopmental disorder, communication problems, and repetitive/stereotypic behaviour are all characteristics of autism, a severe developmental disorder. Even though the pathophysiological causes of autism are still unclear and contested in many cases, genetic and environmental factors (and their interactions) have been identified as contributing factors. While it is widely acknowledged that various factors can cause autism, environmental factors have received a great deal of attention recently. A large part of the international debate has focused on neurotoxins such as Lead, Iron, and Cadmium, with some arguing that these and other toxic metals have a role in the development of the condition. Methods: Between March and December 2020, the study is being performed in Iraq's Al-Anbar province. 75 autistic children and 20 volunteers children served as controls in the study, all of whom had confirmed DSM-V diagnoses. An atomic absorption spectrophotometer is used to test hair samples. Two heavy elements (Lead and Iron) and one trace element (Cadmium) are measured. The results are shown as significant high in Lead ,and Iron concentrations in Autistic compared with Control, and International Normal Value, more than Lead, and Iron considered as risk environment factor for ASD, While a cadmium concentration is expressed significant high in autism and slightly in control compare with International Normal Value, and considered no risk environmental factor in Iraqi populations. It could be due to the pollution of the Iraqi environment.

Background. The genetic deficiency of folate cycle enzymes is considered today as one of the common causes of autism spectrum disorders in children, but the relationship between the genetic components of failures and clinical phenotype was not characterized enough. There is some evidence of immune system involvement in the pathogenesis, including association with immunodeficiencies, cases of autism after neuroinfections and autoimmune encephalitis, the effectiveness of immunotherapy. The purpose was to evaluate the extended clinical and laboratory phenotype in patients with autism spectrum disorders associated with genetically determined deficiency of folate cycle. Materials and methods. A prospective, controlled, single­center study included 78 children diagnosed with autism spectrum disorders and/or cerebral palsy. These were patients from different regions of Ukraine, aged 2 to 10 years, 47 boys and 31 girls. Control group consisted of 34 healthy children with the same age and gender distribution. The identification of gene polymorphisms of folate cycle by polymerase chain reaction, a comprehensive immunological study, diagnosis of infection (polymerase chain reaction, serological tests, microbiological method), determination of biomarkers (biochemical methods) were performed. In order to establish the significant differences of the results, Student’s T­test was used with the calculation of confidence coefficient p (parametric test) and the number of Z signs by Urbach (nonparametric). To study the relationship between polymorphisms of folate cycle genes and the immune status, the Pearson’s chi­squared test ( χ 2 ) was used. Results. The deficiency of NK­ and/or NKT­cells was observed in the study group in 91 % of cases, while among healthy children from the control group, similar immunophenotype occurred only in 27 % of cases, and usually there was a slight decrease in the number of cells (p < 0.05; Z < Z0.05). Deficiency of NK­ and NKT­cells was closely associated with the presence of polymorphisms in the genes of folate cycle enzymes ( χ 2 = 51.1; p = 0.01), as well as demonstrated less pronounced but statistically significant correlation with myeloperoxidase deficiency (p = 0.05). An abnormally reduced resistance to viral agents was shown: lymphotropic herpesviruses, measles and rubella, rotavirus, which can be explained by the immune deficiency. Associated extensive clinical phenotype is characterized that include, in addition to autistic disorders, other immunodependent lesions: chronic viral infections, mesial temporal sclerosis and mesial temporal lobe epilepsy (46 %), PANDAS (27 %), movement disorders (20 %), allergy (32 %) and bowel syndrome (88 %). Leukoencephalopathy, especially that involving periventricular areas of the parietal lobes, associated with neuroinfections and autoimmune reactions, was the main form of damage to the central nervous system (96 %). Conclusions. It is reasonable to talk about the extended clinical and laboratory phenotype in children with genetic folate cycle deficiency associated with autism spectrum disorders that requires a multidisciplinary approach to the management of patients with the mandatory assistance of a clinical immunologist.

It is extremely important to understand the causes of autism spectrum disorder (ASD) which is a neurodevelopmental disease. Treatment and lifelong support of autism are also important to improve the patient's life quality. In this article, several findings were explained to understand the possible causes of ASD. We draw, outline, and describe ASD and its relation with the epigenetic mechanisms. Here, we discuss, several different factors leading to ASD such as environmental, epigenetic, and genetic factors.

The evolution of autism diagnosis, from its discovery to its current delineation using standardized instruments, has been paralleled by a steady increase in its prevalence and heterogeneity. In clinical settings, the diagnosis of autism is now too vague to specify the type of support required by the concerned individuals. In research, the inclusion of individuals categorically defined by over-inclusive, polythetic criteria in autism cohorts results in a population whose heterogeneity runs contrary to the advancement of scientific progress. Investigating individuals sharing only a trivial resemblance produces a large-scale type-2 error (not finding differences between autistic and dominant population) rather than detecting mechanistic differences to explain their phenotypic divergences. The dimensional approach of autism proposed to cure the disease of its categorical diagnosis is plagued by the arbitrariness of the dimensions under study. Here, we argue that an emphasis on the reliability rather than specificity of diagnostic criteria and the misuse of diagnostic instruments, which ignore the recognition of a prototype, leads to confound autism with the entire range of neurodevelopmental conditions and personality variants. We propose centering research on cohorts in which individuals are selected based on their expert judged prototypicality to advance the theoretical and practical pervasive issues pertaining to autism diagnostic thresholds. Reversing the current research strategy by giving more weight to specificity than reliability should increase our ability to discover the mechanisms of autism. LAY SUMMARY: Scientific research into the causes of autism and its mechanisms is carried out on large cohorts of people who are less and less different from the general population. This historical trend may explain the poor harvest of results obtained. Services and intervention are provided according to a diagnosis that now encompasses extremely different individuals. Last, we accept as a biological reality the constant increase over the years in the proportion of autistic people among the general population. These drifts are made possible by the attribution of a diagnosis of autism to people who meet vague criteria, rather than to people who experienced clinicians recognize as autistic. We propose to change our research strategy by focusing on the study of the latter, fewer in number, but more representative of the "prototype" of autism. To do this, it is necessary to clearly distinguish the population on which the research is carried out from that to which we provide support. People must receive services according to their needs, and not according to the clarity of their diagnosis.

Vaccine hesitancy may be more common among parents of children with autism spectrum disorder (ASD). We examined factors associated with ASD-specific vaccine hesitancy among caregivers of children with ASD who participated in the SPARK study (Simons Foundation Powering Autism Research for Knowledge). 225 participants completed an online survey containing the Parent Attitudes About Childhood Vaccines (PACV) questionnaire (measure of vaccine hesitancy) and the Illness Perception Questionnaire revised for parents of children with ASD (IPQ-R-ASD; measure of parents' views about ASD). 65 participants (28.8%) were vaccine hesitant (PACV score ≥ 50); children of vaccine-hesitant parents (VHPs) were less likely to be first born (n = 27, 41.5%), had greater ASD-symptom severity (mean Social Communication Questionnaire score = 23.9, SD = 6.9), and were more likely to have experienced developmental regression (n = 27, 50.9%) or plateau (n = 37, 69.8%). Compared to non-hesitant parents, VHPs significantly more often endorsed accident/injury, deterioration of the child's immune system, diet, environmental pollution, general stress, parents' negative views, parents' behaviors/decisions, parents' emotional state, and vaccines as causes for ASD. VHPs also had higher scores on the Personal Control, Treatment Control, Illness Coherence, and Emotional Representations subscales of the IPQ-R than did non-hesitant parents. In the final model, ASD-related vaccine hesitancy was significantly associated with higher scores on the Emotional Representations subscale (OR = 1.13, p = 0.10), agreement with deterioration of the child's immunity as a cause of ASD (OR = 12.47, p < 0.001), the child not having achieved fluent speech (OR = 2.67, p = 0.17), and the child experiencing a developmental plateau (OR = 3.89, p = 0.002). Findings suggest that a combination of child functioning and developmental history, as well as parents' negative views about and their sense of control over ASD, influence vaccine hesitancy among parents of children with ASD.

David G. Amaral1 and Petrus J. de Vries2 1Department of Psychiatry and Behavioral Sciences, The MIND Institute, UC Davis, Sacramento, California, USA 2Centre for Autism Research in Africa, Division of Child and Adolescent Psychiatry, University of Cape Town, South Africa Last year around this time, in preparation for the INSAR2019 meeting in Montreal, we asked members of the Autism Research editorial board as well as the Associate Editors to write short comments on what they considered to be the major gaps in autism research. The resulting Commentary was well received with nearly 3000 downloads. The INSAR meeting scheduled for Seattle in 2020 was, of course, cancelled due to the coronavirus pandemic. The pandemic has forced the reorganization and rethinking of all science, including autism research. To get a sense of how autism researchers are dealing with this unprecedented situation around the world, we asked for short comments about the situation from editorial board members, Associate Editors and from the INSAR Global Senior Leaders in Autism Research Committee, a relatively new INSAR initiative chaired by Petrus de Vries (South Africa) and Declan Murphy (UK). We will present perspectives by World Health Organization (WHO) Region. Before going further, we must acknowledge that over and above the hardships for autism researchers across the globe, the pandemic has cost so much more to the more than 400,000 families worldwide that have suffered the death of a loved one. We offer our condolences to those families and to those who will befall a similar fate in the future. We also acknowledge the global economic burden of the pandemic, both as a result of COVID‐19 and as a consequence of lockdown. This too will have a major impact on everyone, and perhaps disproportionately so on families who live with disabilities and those in low‐ and middle‐income countries. The contributions that make up the remainder of this commentary are in equal parts frightening and inspiring. On the down side, they talk about the difficulties in conducting autism research when social distancing is in place and when participants must wear masks. How does one recruit young subjects if the ADOS cannot be done with masked individuals? There is also the concern that, given the overall frightening environment of the current situation, it may be difficult to interpret behavioural research results. For example, are measures of anxiety now reflecting a trait of an individual or the state of heightened angst resulting from dealing with the virus? Others worry that the enormous costs of dealing with controlling the spread of the virus will eliminate academic positions and autism research funding in the future. This is a real concern. The state of California has gone from a $14 billion surplus to a projected $54 billion deficit. Public higher education in the state is now slated for a 10% reduction in funding. There are also implications for prevalence of autism in the future. One of the prominent, proposed nongenetic causes of autism is maternal immune activation [Patterson et al., 2011]. Naturally occurring pathogen exposures offer the strongest evidence of environmental etiology. The best example is maternal rubella (German measles) infection during pregnancy. Before development and widespread dissemination of effective vaccines, major pandemics occurred every 10 to 30 years [Duszak, 2009]. The last of these was from 1963 to 1965 and infected an estimated 10 percent of pregnant women, resulting in more than 13,000 fetal or early infant deaths; 20,000 infants born with major birth defects and 10,000 to 30,000 infants born with moderate to severe neurodevelopmental disorders. Stella Chess, a child psychiatrist at New York University, studied 243 children exposed to rubella during pregnancy [Chess, 1971; Chess, 1977] and found that the largest category of neurodevelopmental disorder was intellectual disability, which affected 37 percent of the sample. Nine of these children were also diagnosed with autism; another, without intellectual disability, had a possible diagnosis; and eight a partial syndrome of autism. These numbers would translate to an autism prevalence of 741 per 10,000 rubella‐exposed children, just over seven percent which was strikingly different from the 2‐3 per 10,000 typically found at the time in the general population. It is concerning therefore, that a recent survey of two New York hospitals found that 15% of pregnant woman coming for the delivery of their child were positive for coronavirus [Breslin et al., 2020] and many of these were asymptomatic. Given the inadequate testing in many countries, the true number of pregnant woman infected with the virus may not be known for some time and the implication for the prevalence of autism will undoubtedly be the basis for much future research. But, the contributions below also reflect an up side of resilience and resolve by the autism research community. Many investigators describe how testing and even clinical trials were rapidly converted from in person to telehealth strategies. Development of more efficient and technology driven assessment tools has been fast‐tracked due to the pandemic. Could robots provide a mechanism for providing therapy without the risk of viral exposure? The use of teleconferencing platforms like Zoom have transformed how scientists are communicating their research results leading some to suggest that this may also be a strategy to reduce air travel and global warming in the future. Here too the disparity between access to digital technology in richer countries relative to under resourced countries is amplified. One hopefully positive take‐a‐way message relates to the importance of science in solving problems such as pandemics. The development of diagnostic tests, vaccines and medications related to COVID‐19 highlights the work of the millions of scientists who labor, generally in obscurity, to gather knowledge about the natural world. We hope that you enjoy the thoughtful comments of many of our colleagues who are engaged in research dedicated to decreasing disability in individuals with autism spectrum disorder.

Helsmoortel Van der Aa syndrome also known as ADNP syndrome is a neurological disorder which is caused by genetic changes in the ADNP gene. These genetic mutations occur impulsively in most patients, showing that there has been no family history of the disorder. These mutations mostly affect the intellectual abilities of the person, delays motor planning, and also may lead to autism or autism spectrum disorder. In 2014 ADNP disorder was discovered, and it is found that ADNP gene was one of the most consistent single gene causes of autism. Although several researchers have discovered a clear view with characteristics of the "core" effects associated with several mutations in the ADNP gene, a lot of things about the disorder is still unknown. Detecting ADNP syndrome in a person can be challenging as it is developed spontaneously without a long development curve. For this research of predicting the ADNP syndrome, a dataset comprising the details of 150 children, where 23 were diagnosed with ADNP syndrome and 127 were typically developing (TD) children was taken. The dataset comprises features such as a person's age, sex, whether he/she has been treated with jaundice, and their family history with ADNP and some other additional features.

BACKGROUND AND AIM: Early-life causes of autism spectrum disorders (ASD) are multifactorial, including prenatal air pollution and gestational conditions with maternal immune activation (MIA) which ...

Autism is a neurodevelopmental disorder of complex etiology and is amongst the most heritable of neuropsychiatric disorders while sharing genetic liability with other neurodevelopmental disorders such as intellectual disability (ID). Autism spectrum disorders (ASDs) are defined more broadly and include autism, Asperger syndrome, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified. Under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IVTR), these disorders are grouped together with Rett syndrome (“Rett’s disorder”) as pervasive developmental disorders. However, Rett syndrome has a reportedly distinct pathophysiology, clinical course, and diagnostic strategy (Levy & Schultz, 2009) and will likely be removed in the impending publication of DSM-V (APA, 2010). The new diagnostic manual will formally adopt the single diagnostic category “ASDs”, which is used here. Reported prevalence rates for ASDs range from 20 (Newschaffer et al. 2007) to 116 (Baird et al., 2006) per 10,000 children, and vary in accordance with diagnostic, sampling, and screening criteria. The Centers for Disease Control and Prevention (CDC) suggest that in the United States, the prevalence of ASDs is 1 in 110 (1/70 in boys and 1/315 in girls) (ADDM, 2009). The three primary characteristics of ASDs are communication impairments, social impairments, and repetitive/stereotyped behaviors. The DSM-IVTR, ICD-10, and many other diagnostic instruments require impairment in each of these domains for a diagnosis of autistic disorder. Within the last decade, a number of major technological developments have transformed our understanding of the genetic causes of autism, and the field continues to evolve rapidly. In this chapter, we will review three approaches to identifying genetic factors that contribute to the pathogenesis of ASDs: 1) common variants and genome-wide association studies (GWAS); 2) rare variants and copy number variation (CNV) studies, and 3) familial forms of autism and the role of next-generation sequencing (NGS) methods. Data from all three approaches underscores the conclusion that autism is a highly complex and heterogeneous disorder, involving a multifactorial etiology. Moreover, it is becoming increasingly apparent that autism is not a unitary disorder, and that the spectrum may consist of any number of different autisms that share similar symptoms or phenotypes. This conclusion has important implications for evaluation and treatment, which are discussed in the conclusion.

Lead poisoning is a continuing crisis impacting learning, neurological and behavioral development in children. This study investigated an important outcome from the environmental lead contamination which cause retardation of infant’s brain development. A total of 30 Swiss albino mice of both sexes were used in this study and divide into three groups consisting 6 female and 4 male in each group. Two groups of mice were given lead treated drinking (30 ppm and 230 ppm respectively) and rat pellets ad libitum and the control mice were supplied normal drinking water and rat pellets ad libitum. At 20-21th days of pregnancy lead-induced female mouse gave birth to a litter of 5-6 pups; whereas, control mouse gave birth to 10-13 pups at a time. Both lead-induced and controlled offspring were found normal; however, some lead-induced offspring were found comparatively smaller than the control one. Autism spectrum disorder behavioral diagnostic tools were used to explore the level of autism, if any. The anxiety assessment marble burying investigation did not reveal any significant differences among the group’s mice. Three chambered social interaction analysis found no significant differences among the mice. Blood serum level of lead for controlled mice were found 0.333mg/dL, whereas, 30 ppm and 230 ppm lead-induced born mice were found 3.833mg/dL and 9.666mg/dL respectively. This study suggested that a genetic predisposition pair with exposure to environmental toxicants play important role in the causes of autism spectrum disorder. Lead is not the pivotal factor of autism development in new born offspring in mice&nbsp

Background The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers. Main body This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a “tipping point” at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development. Conclusion Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case–control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism.

Background: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods: Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results: Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions: Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.

Pragmatic language is a characteristic weakness in the language profile of individuals with fragile X syndrome (FXS), the most frequent inherited cause of intellectual disability and among the most common known genetic causes of autism spectrum disorder (ASD). However, pragmatic language profiles in FXS are known to be highly heterogeneous, and influenced by other cognitive factors, sex, and ASD status. In this chapter, we review pragmatic strengths and weaknesses across males and females with FXS, including comparisons with individuals with Down syndrome (another form of intellectual disability) as well as the impact of ASD status on pragmatics in FXS. We also consider the role of related underlying mechanisms (e.g. theory of mind, hyperarousal) that may importantly impact pragmatic language profiles, and discuss sex-specific differences. We conclude this chapter with directions for continued investigation and clinical considerations for assessment and intervention.

Mutations affecting the synaptic-scaffold gene SHANK3 represent the most common genetic causes of autism with intellectual disability, accounting for about 1-2% of cases. Rare variants of this gene have also been associated with schizophrenia, and its deletion results in the autistic condition known as Phelan–McDermid syndrome. Despite the importance of SHANK3 as a paradigmatic gene mediating neurodevelopmental disorders, its psychological effects in nonclinical populations have yet to be studied. We genotyped the nonsynonymous, functional SHANK3 SNP rs9616915 in a large population of typical individuals scored for autism spectrum traits (the Autism Quotient, AQ) and schizotypy spectrum traits (the Schizotypal Personality Questionnaire, SPQ-BR). Males, but not females, showed significant genotypic effects for the SPQ-BR subscale associated with speech and language: Odd Speech. These findings, in conjunction with animal model studies showing vocalization and auditory effects of SHANK3 mutations, and studies indicating severe language alterations and speech-associated white matter tract abnormalities in Phelan–McDermid syndrome, suggest that SHANK3 differentially affects the development and expression of human language and speech. Imaging genetic and speech-language studies of typical individuals carrying different genotypes of rs9616915 should provide novel insights into the neurological and psychological bases of speech and language alterations among individuals with SHANK3 mutations and Phelan–McDermid syndrome.

Duplications of chromosome 16p11.2, even though rare in the general population, are one of the most frequent known genetic causes of autism spectrum disorder and of other neurodevelopmental disorders. However, data about the neuro-behavioral phenotype of these patients are few. We described a sample of children with duplication of chromosome 16p11.2 focusing on the neuro-behavioral phenotype. The five patients reported presented with very heterogeneous conditions as for characteristics and severity, ranging from a learning disorder in a child with normal intelligence quotient to an autism spectrum disorder associated with an intellectual disability. Our case report underlines the wide heterogeneity of the neuropsychiatric phenotypes associated with a duplication of chromosome 16p11.2. Similarly to other copy number variations that are considered pathogenic, the wide variability of phenotype of chromosome 16p11.2 duplication is probably related to additional risk factors, both genetic and not genetic, often difficult to identify and most likely different from case to case.

Efforts to identify the causes of autism spectrum disorders have highlighted the importance of both genetics and environment, but the lack of human models for many of these disorders limits researchers’ attempts to understand the mechanisms of disease and to develop new treatments. Induced pluripotent stem cells offer the opportunity to study specific genetic and environmental risk factors, but the heterogeneity of donor genetics may obscure important findings. Diseases associated with unusually high rates of autism, such as SCN2A syndromes, provide an opportunity to study specific mutations with high effect sizes in a human genetic context and may reveal biological insights applicable to more common forms of autism. Loss-of-function mutations in the SCN2A gene, which encodes the voltage-gated sodium channel NaV1.2, are associated with autism rates up to 50%. Here, we review the findings from experimental models of SCN2A syndromes, including mouse and human cell studies, highlighting the potential role for patient-derived induced pluripotent stem cell technology to identify the molecular and cellular substrates of autism.

Approximately one-fourth of autism spectrum disorder (ASD) cases are associated with a disruptive genetic variant. Many of these ASD genotypes have been described previously, and are characterized by unique constellations of medical, psychiatric, developmental, and behavioral features. Development of precision medicine care for affected individuals has been challenging due to the phenotypic heterogeneity that exists even within each genetic subtype. In the present study, we identify developmental milestones that predict cognitive and adaptive outcomes for five of the most common ASD genotypes. Sixty-five youth with a known pathogenic variant involving ADNP, CHD8, DYRK1A, GRIN2B, or SCN2A genes participated in cognitive and adaptive testing. Exploratory linear regressions were used to identify developmental milestones that predicted cognitive and adaptive outcomes within each gene group. We hypothesized that the earliest and most predictive milestones would vary across gene groups, but would be consistent across outcomes within each genetic subtype. Within the ADNP group, age of walking predicted cognitive outcomes, while age of first words predicted adaptive behaviors. Age of phrases predicted adaptive functioning in the CHD8 group, but cognitive outcomes were not clearly associated with early developmental milestones. Verbal milestones were the strongest predictors of cognitive and adaptive outcomes for individuals with mutations to DYRK1A, GRIN2B, or SCN2A. These trends inform decisions about treatment planning and long-term expectations for affected individuals, and they add to the growing body of research linking molecular genetic function to brain development and phenotypic outcomes. LAY SUMMARY: Researchers have found many genetic causes of autism including mutations to ADNP, CHD8, DYRK1A, GRIN2B, and SCN2A genes. We found that each genetic cause had different early developmental milestones that explained the overall functioning of the children when they were older. Depending on the genetic cause, the age that a child first starts walking and/or talking may help to better understand and support a child's development who has a mutation to one of the above genes. Autism Res 2020, 13: 1659-1669. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

An unbiased, widely accepted estimate of the rate of occurrence of new cases of autism over time would facilitate progress in understanding the causes of autism. The same may also apply to other disorders. While incidence is a widely used measure of occurrence, birth prevalence—the proportion of each birth year cohort with the disorder—is the appropriate measure for disorders and diseases of early childhood. Studies of autism epidemiology commonly speculate that estimates showing strong increases in rate of autism cases result from an increase in diagnosis rates rather than a true increase in cases. Unfortunately, current methods are not sufficient to provide a definitive resolution to this controversy. Prominent experts have written that it is virtually impossible to solve.This paper presents a novel method, time-to-event birth prevalence estimation (TTEPE), to provide accurate estimates of birth prevalence properly adjusted for changing diagnostic factors. It addresses the shortcomings of prior methods. TTEPE is based on well-known time-to-event (survival) analysis techniques. A discrete survival process models the rates of incident diagnoses by birth year and age. Diagnostic factors drive the probability of diagnosis as a function of the year of diagnosis. TTEPE models changes in diagnostic criteria, which can modify the effective birth prevalence when new criteria take effect. TTEPE incorporates the development of diagnosable symptoms with age. General-purpose optimization software estimates all parameters, forming a non-linear regression. The paper specifies all assumptions underlying the analysis and explores potential deviations from assumptions and optional additional analyses.A simulation study shows that TTEPE produces accurate parameter estimates, including trends in both birth prevalence and the probability of diagnosis in the presence of sampling effects from finite populations. TTEPE provides high power to resolve small differences in parameter values by utilizing all available data points.

Background Parents’ perceptions about cause of autism spectrum disorder (ASD) influences their behaviors (e.g., treatment selection, vaccinations). The Revised Illness Perception Questionnaire for ASD (IPQ-R-ASD) offers a systematic way to measure parent parents’ perceptions of ASD cause, but further study is needed. Method Using principal component analysis (PCA), we investigated the factor structure of the IPQ-R-ASD Cause scale, which was administered online, in a sample of 326 North American parents (287 mothers [88 %], 39 fathers) raising children with confirmed ASD diagnoses. Results Six factors emerged on the Cause subscale and were labeled Personal Attributions, Parental Risk Factors, Environmental Risk Factors, Utero/Birth Stress, Biophysiological, and Metaphysical. Together, these factors accounted for a cumulative variance of 61.4 %. All items exceeded the minimum loading to be considered robust, and all but one loaded positively (i.e., “Will of God). Conclusions Understanding parental perceptions about the cause of their children’s ASD may help researchers and clinicians understand important aspects of raising a child with ASD, such as stress and coping responses, treatment selection and implementation, or shared decision-making about service use. Since measurement of causal beliefs is an important initial step in this direction, the current study is helpful in establishing the viability of a measure that may extend this line of research and, ultimately, the instrument’s clinical utility.

Employing the machine learning method, this study analyses 6504 articles from four major newspapers, New York Times , Washington Post , USA Today , and The Guardian , to examine how media cover the topic about causes of autism. A total of 14,305 causal sentences on the topic are extracted from media articles and subjected to analysis of causal entities and descriptions. Results show media have presented multiple factors (e.g. vaccination, genetics, and parenting) pertaining to the causes of autism, as well as multiple symptoms of autism. Most of those causal relationships are presented in a tentative or uncertain manner. The study also reveals significant differences in reportage of autism causation across time and media channels.

According to WHO data, about 67 million people worldwide are affected by autism, and this number grows by 14% annually. Among the possible causes of autism are genetic modifications, organic lesions of the central nervous system, metabolic disorders, influence of viral and bacterial infections, chemical influence to the mother's body during pregnancy, etc. The conducted research shows that research papers published until today do not name any potential protein markers that meet the requirements of the basic parameters for evaluating the efficiency of disease diagnostics, in particular high sensitivity, specificity, and accuracy. Conducting proteomic research on a big scale in order to detect serologic markers of protein nature associated with development of autism spectrum disorders seems to be highly relevant.

Autism is a psychiatric disorder of unknown aetiology. In this article, the literature on genetic, neurological, psychological, relational and cultural causes of autism is reviewed, beginning with the 2014 review of Crittenden, Dallos, Landini et al. (pp. 64–70) up to and including recent publications in 2017. Some of the findings were unexpected; others led to new questions. The unexpected findings were the minimal contribution of genes to autism, the extremely evident neurological differences, the interpersonal quality of the psychological findings (that lacked evidence of parents’ behaviour), the relational evidence that mothers’ childhood trauma, perinatal stress and marital stress increased the risk of autism, and the reciprocal relation between funding for treatment of autism and diagnoses of autism. Notably, there was an abundance of genetic studies, numerous neurological studies and only scattered psychological, relational and cultural studies, thus rendering those findings speculative. The new questions included whether mothers used postural/gestural signs to signal their children to maintain distance and whether mothers experienced wariness of males as a result of childhood trauma, with their sons possibly experiencing gender confusion. Following the literature review, a small archival set of video-recorded and transcribed assessments of attachment of cases of autism were examined for evidence to corroborate or refute the psychological and relational findings of the literature review. The findings were striking in their support of mothers’ use of postural/gestural communication regarding distance, children’s close attention to mothers’ bodily signals, without looking at mothers’ face, mothers’ greater comfort when they approached their sons than when their sons approached them, one boy’s lack of verbal self-representation and mothers’ childhood triangulation. These became hypotheses regarding what to look for in Part 2 of this article, a prospective, 12-year case study.

In the past, the behaviours and personalities of mothers have been identified as potential causes of autism. More recently, other etiological hypotheses have been used to explain autism spectrum di...

Although germline de novo copy number variants are a known cause of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. Here, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 ASD probands and 5,500 unaffected siblings in the Simons Simplex Collection (SSC) and Simons Powering Autism Research for Knowledge (SPARK) cohorts. We detected 46 mCNVs in probands and 19 mCNVs in siblings ranging from 49 kb to 249 Mb and affecting 2.8-73.8% of cells. In both cohorts, probands carried a significant burden of large (>4 Mb) mCNVs (P = 0.043 and P = 6.6 × 10−3 in SSC and SPARK, respectively), which were present in a total of 25 probands but only 1 sibling (OR=11.4, 95% CI=1.5-84.2). Surprisingly, we did not observe mosaic analogues of the short de novo CNVs recurrently observed in ASD. Event size positively correlated with severity of ASD symptoms (P = 0.016), and four probands exhibited clinical symptoms consistent with syndromes previously associated with genes or regions disrupted by their respective mosaic mutations. In analyses of post-mortem brain tissue from 60 additional probands, we further detected and experimentally validated two mCNVs including a complex 10.3 Mb duplication on chromosome 2. These results indicate that mosaic CNVs contribute a previously unexplained component of ASD risk.

Autism spectrum condition (ASC) is a complex set of behavioral and neurological responses reflecting a likely interaction between autism susceptibility genes and the environment. Autism represents a spectrum in which heterogeneous genetic backgrounds are expressed with similar heterogeneity in the affected domains of communication, social interaction, and behavior. The impact of gene-environment interactions may also account for differences in underlying neurology and wide variation in observed behaviors. For these reasons, it has been difficult for geneticists and neuroscientists to build adequate systems to model the complex neurobiology causes of autism. In addition, the development of therapeutics for individuals with autism has been painstakingly slow, with most treatment options reduced to repurposed medications developed for other neurological diseases. Adequately developing therapeutics that are sensitive to the genetic and neurobiological diversity of individuals with autism necessitates personalized models of ASC that can capture some common pathways that reflect the neurophysiological and genetic backgrounds of varying individuals. Testing cohorts of individuals with and without autism for these potentially convergent pathways on a scalable platform for therapeutic development requires large numbers of samples from a diverse population. To date, human induced pluripotent stem cells (iPSCs) represent one of the best systems for conducting these types of assays in a clinically relevant and scalable way. The discovery of the four Yamanaka transcription factors (OCT3/4, SOX2, c-Myc, and KLF4) [1] allows for the induction of iPSCs from fibroblasts [2], peripheral blood mononuclear cells (PBMCs, i.e. lymphocytes and monocytes) [3, 4], or dental pulp cells [5] that retain the original genetics of the individual from which they were derived [6], making iPSCs a powerful tool to model neurophysiological conditions. iPSCs are a readily renewable cell type that can be developed on a small scale for boutique-style proof-of-principle phenotypic studies and scaled to an industrial level for drug screening and other high-content assays. This flexibility, along with the ability to represent the true genetic diversity of autism, underscores the importance of using iPSCs to model neurophysiological aspects of ASC.

Autism is one of the neurological disorders that occurs in children. There are many causes of autism, one of which is genetic factors. Therefore, in order to find effective treatments, we need to discover the genes which relate to autism disease. In this paper, we use a computational approach to train a model that can predict new autism-related candidate genes. The methodology combines different data sources such as protein-protein interaction networks, microRNAs (miRNA)-target network and known autism-related genes into an integrated network. The structural properties of this network are represented as a vector dataset and a binary classification problem is formulated. However, because the number of known autism-related genes is very small, we face an imbalance data classification problem. To solve this issue, an under-sampling clustering-based data balancing algorithm has been proposed. Training classifiers with machine learning models such as SVMs, k-NN, and RFs, we obtained results of 1-3% higher in G-mean measures when comparing to cases without using any data balancing strategies. These results implied that our proposed model may contribute to finding new autism-related gene candidates.

Background Fear of autism has led to a decline in childhood-immunization uptake and to a resurgence of preventable infectious diseases. Identifying characteristics of parents who believe in a causal role of vaccines for autism spectrum disorder (ASD) in their child may help targeting educational activities and improve adherence to the immunization schedule. Objectives To compare caregivers of children with ASD who agree or disagree that vaccines play an etiological role in autism for 1) socio-demographics characteristics and 2) developmental and clinical profiles of their children. Methods Data from 16,525 participants with ASD under age 18 were obtained from SPARK, a national research cohort started in 2016. Caregivers completed questionnaires at registration that included questions on beliefs about the etiologic role of childhood immunizations and other factors in ASD. Data were available about family socio-demographic characteristics, first symptoms of autism, developmental regression, co-occurring psychiatric disorders, seizures, and current levels of functioning. Results Participants with ASD were 80.4% male with a mean age of 8.1 years (SD = 4.1). Overall, 16.5% of caregivers endorsed immunizations as perceived causes of autism. Compared to caregivers who disagreed with vaccines as a cause for ASD, those who believed in vaccine causation came disproportionately from ethnic minority, less educated, and less wealthy backgrounds. More often their children had experienced developmental regression involving language and other skills, were diagnosed earlier, had lost skills during the second year of life, and had worse language, adaptive, and cognitive outcomes. Conclusion One in six caregivers who participate in a national research cohort believe that child immunizations could be a cause of autism in their child. Parent social background (non-White, less educated) and child developmental features (regression in second year, poorer language skills, and worse adaptive outcomes) index caregivers who are more likely to harbor these beliefs and could benefit from targeted educational activities.

Autism spectrum disorder is a neurodevelopmental condition in which affected individuals have difficulties while interacting and communicating socially, and repetitive behaviors. It has a multifactorial etiology. Various risk factors, including genetic and environmental influences, have been explored while trying to understand its causation. As older evidence was suggestive of a high heritability, a majority of research focused on finding the underlying genetic causes of autism. Due to these efforts, there have been advances in the knowledge of some of the genetic factors associated with autism. But a recent trend also shows an increasing interest in exploration of various potential environmental triggers. These efforts have brought us closer to understanding the elusive disorder more so than ever before. The current review discusses the recent trends in research exploring the etiopathogenesis of autism spectrum disorder.

Background In the search for the causes of autism spectrum disorders (ASD), inflammatory markers have emerged as potential candidates. The present meta-analysis was performed on studies examining circulating concentrations of anti-inflammatory cytokines in people with ASD compared with control subjects without ASD. Methods We identified potentially eligible studies by systematically searching electronic databases from inception to February 2018. Results Twenty-five studies with a total of 1754 participants (1022 patients with ASD and 732 control subjects) were included in the mate-analysis; 4 for interferon (IFN)-α, 9 for interleukin (IL)-1 receptor antagonist (Ra), 9 for IL-4, 6 for IL-5, 3 for IL-9, 14 for IL-10, 7 for IL-13, and 6 for transforming growth factor (TGF)-β. We found a moderate decrease in plasma levels of IL-10 (SMD = −0.59) and a small decrease in serum levels of IL-1Ra (SMD = −0.25) in patients with ASD. On the contrary, serum IL-5 levels were slightly increased (SMD = 0.26) in these patients. We conducted meta-regression analyses to investigate the possible effect of moderatos on the effect size (ES) of difference in mean levels of IL-10. Difference in the mean age between patients and controls showed a negative influence on the ES and was able to explain about 0.4 of total between-study variance. In contrast, latitude exerted a positive effect on the ES and explained a lower proportion (0.1) of total between-study variance. Conclusions This meta-analysis provides evidence for the lower concentration of anti-inflammatory cytokines IL-10 and IL-1Ra in autistic patients compared with control subjects. Also, meta-regression analyses point to the interaction of latitude, age, and gender with peripheral alterations of associated anti-inflammatory cytokines.

Identification of the biological features of autism is essential for designing an efficient treatment and for prevention of the disorder. Though the subject of extensive research, the neurophysiological features of autism remain unclear. One of the proposed biological causes of autism is malfunction of the pineal gland and deficiency of its principal hormone, melatonin. The main function of melatonin is to link and synchronize the body's homeostasis processes to the circadian and seasonal rhythms, and to regulate the sleep-wake cycle. Therefore, pineal dysfunction has been implicated based on the common observation of low melatonin levels and sleep disorders associated with autism. In this perspective, we highlight several recent findings that support the hypothesis of pineal gland/melatonin involvement in autism. Another common symptom of autism is abnormal neuroplasticity, such as cortical overgrowth and dendritic spine dysgenesis. Here, we synthesize recent information and speculate on the possibility that this abnormal neuroplasticity is caused by hyperactivity of endogenous N,N-dimethyltryptamine (DMT). The pineal gland was proposed as the source of DMT in the brain and therefore, our assumption is that besides melatonin deficiency, pineal dysfunction might also play a part in the development of autism through abnormal metabolism of DMT. We hope that this manuscript will encourage future research of the DMT hypothesis and reexamination of several observations that were previously attributed to other factors, to see if they could be related to pineal gland/melatonin malfunction. Such research could contribute to the development of autism treatment by exogenous melatonin and monitored light exposure.

Cultural beliefs about parenting have an important influence on parenting behaviours, including considerations about appropriate ways to parent children with autism. Although Indonesia has one of the largest and most ethnically diverse populations in the world, little is known about cultural beliefs regarding children with autism within Indonesian cultures. The goal of the present study was to investigate how Indonesian mothers from a range of backgrounds and without a child with autism understood autism and the most appropriate ways to parent such a child. The study was a qualitative investigation using semi-structured interviews with nine Indonesian mothers. Five aspects were investigated: understanding about autism, beliefs about causes of autism, possible reactions to having a child with autism, perceptions of parenting a child with autism, and perceptions of parent-child relationships. The interviews revealed five related themes about autism, including traditional cultural beliefs about appro...

Background: There are conflicting reports on the prevalence of ASDs in mainland China (China thereafter) and abroad, and no scholars have compared the prevalence in China and abroad. Further studies are needed to clarify the changes in the prevalence rate and compare the prevalence rates at home and abroad. Objective: In order to compare the prevalence of autism at home and abroad, and compare diagnostic tools, diagnostic criteria and other aspects. So far, no scholar has compared the prevalence of autism in China and abroad. Chinese scholars have hardly studied the comprehensive prevalence in China, and the prevalence of autism is conflicting. Methods: I used the Meta-analysis to carry out the research. Firstly, literature was retrieved according to key words and extracted according to screening criteria. Secondly, forest plots and funnel plots were drawn to analyze their significance and heterogeneity. Results: Based on diagnostic criteria the pooled prevalence of ASDs, 73.6 per 10,000 in China (95% CI: 14.22-77.96 per 10,000 I2 = 80.95%), and 98.8 per 10,000 abroad (95% CI: 22.35-127.04 per 10000 per 98.14%, I2 = 98.14%). Subgroup analyses revealed significant difference in the prevalence of ASDs between genders. Moreover, the prevalence of males far exceeds that of females both in China and abroad. Conclusion: There are significant differences in the prevalence of autism at home and abroad, and there are also large differences in diagnostic criteria and diagnostic tools. There are significant differences between developing regions and underdeveloped regions, and there are also differences in the prevalence of autism between different genders, but the differences are not significant. In addition, the number of people suffering from autism may gradually increase in the future, and the number of people who understand autism will become wider and wider, the aging phenomenon of autism will gradually increase, and the causes of autism will become more and more complicated.

Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure.

Autism spectrum disorder (ASD) is one of the prominent and complex neurodevelopment disorders that are rising around the globe. In India, the autism rate has grown and now about 1 out of 88 children is prone to autism. ASD is associated with various problems such as low vision clarity, communication difficulties, repetitive behavior, insecure emotions, sensory issues, uninterested behavior, etc. Many researchers work towards the identification of major causes of autism and various impacts of the disorder. Although the basic causes and mechanism behind ASD could not be completely identified, it is obvious that the abnormal neurotransmission in brain regions prevents the child from normal behavior and motor actions and leads to an altered behavior. This impairment of mental difficulties could be identified with regular periodic analysis of the child communication behavior, social interaction, object identification, emotional sequence, linguistic ability and knowledge adaptation rate between the ages of 10 months to 3 years. The major pitfall in the ASD is that people from rural areas are not aware of the factors, causes and behavioral changes in the child with ASD. This leads to poor and misleading training and guiding the children for their future. Also the clinical analysis involves numerous trials to analyze the autistic characteristics across children age. Such clinical analysis could be made faster with the computer vision, thus resulting in early identification of autism. This chapter mainly focuses on the emotional sequence identification of children who are ASD positive and ASD negative (i.e., normal TD). The first screening is made through the facial expression analysis in children identified as ASD positive and TD. The methodology involved in facial detection and feature analysis is Viola–Jones algorithm and facial landmark vectorization, respectively. The facial expression is then classified using an SVM linear classifier. The facial expressions of ASD and TD are compared to identify the variations in facial expressions of children. This level of screening through expression identification is made in a contactless environment as children may get influenced by the object they face. The second level of improvement in screening involves a deep learning technique to identify the children facial expressions and emotion using facial landmark analysis. The former involves plotting up of 68 points on the face identified though landmark detection. In the later methodology, computational neural network technique is employed to identify the correlation between the points for facial emotion analysis. This improves the performance of analysis in emotion identification in children in the same contactless environment. The ultimate aim of the paper is to design a complete combinatorial model for the results from various screening experiments involving a multimodal deep learning technique that projects to a better solution of autism identification. The multimodal technique is planned to take input from the screenings 1 and 2 simultaneously as initial neurons, x, and form a hidden layer, h, by selecting the appropriate neuron in fine-tuning the cross-neuron activation function. The experimental analysis identifies (i) the expression showed by every autistic child, (ii) the major expression observed among the children with ASD, (iii) expression change in a child and the pattern of expression, and (iv) expression analysis through SVM and CNN learning methods. The experimental analysis boosts in training the autistic child on a proper streamline, which helps the parent and trainer in bringing up the child to reach heights.

Autism is a behaviorally defined neurodevelopmental disease characterized by social communication and social interaction deficits, as well as repetitive behaviors and restricted interests. Although the causes of autism are extremely complex, involving genes, environments and gene-environment interactions, genetic mutations are the important risk factors. For this reason, preclinical research is now shifting into focusing on generating transgenic and knockout models, especially using macaques, which are the closest relatives to humans. In spite of unique advantages of macaques over rodents in both functionally specialized brain structures and highly sophisticated social behaviors, the limited availability of phenotype screening tools restricts their translational utility. Here, this review focuses specially on behavioral phenotyping assays for macaque models of autism. In the first part, the existing behavioral tests are discussed, and the second part is devoted to some few, in our view, very promising tests of new developments. In years to come, we should develop macaque models with high construct validity, improve face validity by designing more specialized behavioral screening tools, strengthen collaborative efforts between rodent and macaque models, and ultimately translate the results from animal models into human clinical trials.

The healthcare environment is generally recognized as being information rich, with a knowledge poor. Despite the existence of a huge amount of data collected in medical records, however, the trends, patterns, and relationships between the crucial causes of Autism Disorder (AD) remain undetected. Knowledge of the risk factors associated with AD helps healthcare professionals to identify patients at high risk of having the AD. The aim of this research is to use data mining techniques, namely classification, to analyze and understand risk factors for the incident of autism in Saudi Arabia. This is achieved through building a classification model that predict the chances of having an autistic child for certain parents. This research contributes to emphasizing 13 risk factors that have been considered as potential for the occurrence of autism in previous studies. Two approaches of classification were used; incremental and non-incremental learning algorithms. The performance of different classification algorithms was compared in terms of classifier’s accuracy, precision, and recall. IBK algorithm produces the better average accuracy for the classifier followed by RandomForest which is $80.6 \%$ and 78.3% respectively. Implementation steps and the main user interfaces of the proposed system are presented. Finally, some interesting rules were derived from J48 Decision Tree.

Background: Adequate knowledge and awareness about childhood autism allows early diagnosis and interventions. The present study was carried out to assess the knowledge and perception of university students about childhood autism. Methods: A cross-sectional study was conducted to evaluate the level of knowledge and awareness about autism spectrum disorder among university students. A total of 400 students were randomly enrolled from five universities. The questionnaire covered the major aspects of autism. Results: Only 300 questionnaires were fully completed giving a response rate of 75%. The majority of respondents agreed that autism is a neuro-developmental disorder with strong genetic basis where family history increases chances of developing autism. They believe that vaccination, poor parenting and environmental factors are not causes of autism. Large numbers of participants were not sure if autism is more common in males than females but agreed that early identification improves the therapeutic outcomes while 44% believed that children can outgrow autism with proper treatment. More than 50% of respondents disagreed to the statements that autistic children are intellectually disabled and all display poor eye contact. Only 20% of students agreed that autistics children have mental disabilities, while about 50% believed that they can live independently. Conclusions: University students seem to hold adequate knowledge about major hallmarks of the disorder. However, more efforts are needed to enhance awareness of not only parents and relatives but also the general public so that they can deal responsibly with identified cases of autistic children.

Fragile X syndrome (FXS) is the most common form of familial mental retardation and one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the CGG repeats in the promoter region of the FMR1 gene resulting in the transcriptional silencing of the gene in the pathophysiology of Fragile X syndrome was hypothesized. 23 male patients affected by Fragile X syndrome (full mutation in the FMR1 gene) and 24 controls were included in the study. The serum levels of HDL-C were lower in FXS patients (p

Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well as epigenetic, mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here, we identify the bromodomain and extraterminal domain–containing proteins (BETs) as epigenetic regulators of genes involved in ASD-like behaviors in mice. We found that the pharmacological suppression of BET proteins in the brain of young mice, by the novel, highly specific, brain-permeable inhibitor I-BET858 leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome. Many of the I-BET858–affected genes have been linked to ASD in humans, thus suggesting the key role of the BET-controlled gene network in the disorder. Our studies suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.

Fragile X syndrome (FXS) is a common form of mental disability characterized by hypersensitivity to sensory stimuli, hyperactivity and severe cognitive impairment. FXS is caused by loss of the fragile X mental retardation 1 ( FMR1 ) gene, whose fragile X mental retardation protein (FMRP) regulates mRNA translation downstream of synaptic activity to modulate changes in synaptic architecture, function and plasticity. FXS is one of the known causes of autism and there is no effective treatment that corrects the deficit in FMRP. However, new advances in the knowledge of the molecular pathophysiology of FXS have opened different strategies for the future development of effective drugs. Among the emerging targets are several protein kinases, neuronal calcium sensors, muscarinic receptors, potassium channels, endocannabinoid system, etc. Moreover, some small molecules such statins, antioxidants, glycogen synthase kinase 3 inhibitors among others have showed an improved in cognition and behavioral tests in FXS mouse model emerging as promising drug candidates for FXS pharmacological treatment in the next future.

The causes of autism spectrum disorder (ASD) are not well known. Recent investigations have suggested that air pollution, including PM2.5, may play a role in the onset of this condition. The objective of the present work was to investigate the association between prenatal and early childhood exposure to fine particulate matter (PM2.5) and risk for childhood ASD. A population-based case-control study was conducted in children born between January 1, 2005 and December 31, 2009 in six counties in Southwestern Pennsylvania. ASD cases were recruited from specialty autism clinics, local pediatric practices, and school-based special needs services. ASD cases were children who scored 15 or above on the Social Communication Questionnaire (SCQ) and had written documentation of an ASD diagnosis. Controls were children without ASD recruited from a random sample of births from the Pennsylvania state birth registry and frequency matched to cases on birth year, gender, and race. A total of 217 cases and 226 controls were interviewed. A land use regression (LUR) model was used to create person- and time-specific PM2.5 estimates for individual (pre-pregnancy, trimesters one through three, pregnancy, years one and two of life) and cumulative (starting from pre-pregnancy) key developmental time periods. Logistic regression was used to investigate the association between estimated exposure to PM2.5 during key developmental time periods and risk of ASD, adjusting for mother's age, education, race, and smoking. Adjusted odds ratios (AOR) were elevated for specific pregnancy and postnatal intervals (pre-pregnancy, pregnancy, and year one), and postnatal year two was significant, (AOR=1.45, 95% CI=1.01-2.08). We also examined the effect of cumulative pregnancy periods; noting that starting with pre-pregnancy through pregnancy, the adjusted odds ratios are in the 1.46-1.51 range and significant for pre-pregnancy through year 2 (OR=1.51, 95% CI=1.01-2.26). Our data indicate that both prenatal and postnatal exposures to PM2.5 are associated with increased risk of ASD. Future research should include multiple pollutant models and the elucidation of the biological mechanism for PM2.5 and ASD.

There is no reported investigation comparing concordance in attitudes and beliefs about autism spectrum disorder between parents of children with autism spectrum disorder and scientists who research autism spectrum disorder. To investigate the level of concordance between these groups on causes of autism, priorities of research, perceived stigma, and disclosure of genetic test results, telephone interviews were conducted. Parents (n = 502) were recruited from the Simons Simplex Collection, and research scientists (n = 60) were recruited from investigators funded by the Simons Foundation. Response rates were notable (parents 91%, scientists 80%). Parents and scientists differed significantly regarding beliefs of the likely major cause of autism (p = 0.007) and priorities for further research (p

Objective Although the benefits of vaccines are widely recognized by medical experts, public opinion about vaccination policies is mixed. We analyze public opinion about vaccination policies to assess whether Dunning-Kruger effects can help to explain anti-vaccination policy attitudes. Rationale People low in autism awareness – that is, the knowledge of basic facts and dismissal of misinformation about autism – should be the most likely to think that they are better informed than medical experts about the causes of autism (a Dunning-Kruger effect). This “overconfidence” should be associated with decreased support for mandatory vaccination policies and skepticism about the role that medical professionals play in the policymaking process. Method In an original survey of U.S. adults (N = 1310), we modeled self-reported overconfidence as a function of responses to a knowledge test about the causes of autism, and the endorsement of misinformation about a link between vaccines and autism. We then modeled anti-vaccination policy support and attitudes toward the role that experts play in the policymaking process as a function of overconfidence and the autism awareness indicators while controlling for potential confounding factors. Results More than a third of respondents in our sample thought that they knew as much or more than doctors (36%) and scientists (34%) about the causes of autism. Our analysis indicates that this overconfidence is highest among those with low levels of knowledge about the causes of autism and those with high levels of misinformation endorsement. Further, our results suggest that this overconfidence is associated with opposition to mandatory vaccination policy. Overconfidence is also associated with increased support for the role that non-experts (e.g., celebrities) play in the policymaking process. Conclusion Dunning-Kruger effects can help to explain public opposition to vaccination policies and should be carefully considered in future research on anti-vaccine policy attitudes.

Objective: Genetic, epigenetic, and environmental factors such as infections have been proposed as potential causes of autism spectrum disorder (ASD). Searching for the molecular mechanism by which infections might contribute to the etiopathogenesis of ASD, we analyze here the hypothesis that immune responses to infectious agents may cross-react with human proteins that, when altered, relate to autistic neurodevelopmental spectrum disorders. Methods: Viral and human proteins were analyzed for peptide sharing using the Pir Peptide Match resource. Results: We find that: (i) an intense peptide overlap occurs between ASD–related viruses and ASD–related human proteins, and might underlie cross-reactivity scenarios following viral infections; (ii) viral peptide sharing also occurs with Y-linked proteins, in this way highlighting an additional potential cross-reactivity burden that would involve male subjects only; (iii) many shared peptides are also part of epitopes experimentally validated as immunopositive in the human host. Conclusion: This study offers a cohesive set of data that suggests a contribution of immune cross-reactivity to the genesis of ASD.

One of the earliest theories about the causes of autism is that it occurs from poor parenting or more specifically from the parents’ failure to form an attachment or bond with their child in the early months of his/her life. Known as the “refrigerator mother” myth, this theory gained widespread popularity in the 1960s and led many parents and professionals to believe that parents of autistic children were negligent and responsible for their child’s autistic symptomology. This chapter will explore the origins of the “refrigerator mother” myth, unpack the current research on interactions and attachment between parents and autistic children, and assess its current impact on autistic individuals, their parents and families. In particular, the resulting stress and isolation experienced by parents will be discussed. The chapter will conclude with recommendations for making the transition from placing the blame and burden on parents for their child’s difficulties, towards creating supportive structures so that parents can build their child’s competence.

A popular myth about autism is the belief that vaccinations administered during childhood contribute to the development of autism spectrum disorder. This chapter will unpack the origins of this myth, beginning with a discussion of Wakefield and colleagues’ controversial 1998 study, which received widespread media attention. The media’s portrayal of the vaccination–autism controversy will then be examined, followed by a review of the research on known contributors or causes of autism spectrum disorder. The impact of this myth on creating a culture of fear will be discussed, and the ways this has resulted in the devaluing of autistic people and their potential contributions to society will be explored. A future perspective will be offered, which challenges the belief held by some that autistic children have limited potential because of their autistic differences and allows them to view autistic differences in a positive light. Finally, suggestions will be made for reworking this myth in the light of current research on the impact that autistic individuals have made in today’s world and the positive and negative aspects of life on the autism spectrum.