Socioeconomic Disparities and Prevalence of Autism Spectrum Disorders and Intellectual Disability

Background and Objectives

Study of the impact of socioeconomic status on autism spectrum disorders (ASD) and severe intellectual disabilities (ID) has yielded conflicting results. Recent European studies suggested that, unlike reports from the United States, low socioeconomic status is associated with an increased risk of ASD. For intellectual disabilities, the links with socioeconomic status vary according to the severity. We wished to clarify the links between socioeconomic status and the prevalence of ASD (with or without ID) and isolated severe ID.

Methods

500 children with ASD and 245 children with severe ID (IQ <50) aged 8 years, born 1995 to 2004, were recruited from a French population-based registry. Inclusions were based on clinical diagnoses reported in medical records according to the International Classification of Diseases, 10^th Revision. Socioeconomic status was measured by indicators available at block census level which characterize the population of the child’s area of residence. Measures of deprivation, employment, occupation, education, immigration and family structure were used. Prevalences were compared between groups of census units defined by the tertiles of socioeconomic level in the general population.

Results

Prevalence of ASD with associated ID was higher in areas with the highest level of deprivation and the highest percentage of unemployed adults, persons with no diploma, immigrants and single-parent families. No association was found when using occupational class. Regarding ASD without associated ID, a higher prevalence was found in areas with the highest percentage of immigrants. No association was found for other socioeconomic indicators. The prevalence of isolated severe ID was likely to be higher in the most disadvantaged groups defined by all indicators.

Conclusion

The prevalence of ASD with associated ID and of severe isolated ID is more likely to be higher in areas with the highest level of deprivation.     

Intellectual Disability Is Associated with Increased Runs of Homozygosity in Simplex Autism

Intellectual disability (ID), often attributed to autosomal-recessive mutations, occurs in 40% of autism spectrum disorders (ASDs). For this reason, we conducted a genome-wide analysis of runs of homozygosity (ROH) in simplex ASD-affected families consisting of a proband diagnosed with ASD and at least one unaffected sibling. In these families, probands with an IQ ≤ 70 show more ROH than their unaffected siblings, whereas probands with an IQ > 70 do not show this excess. Although ASD is far more common in males than in females, the proportion of females increases with decreasing IQ. Our data do support an association between ROH burden and autism diagnosis in girls; however, we are not able to show that this effect is independent of low IQ. We have also discovered several autism candidate genes on the basis of finding (1) a single gene that is within an ROH interval and that is recurrent in autism or (2) a gene that is within an autism ROH block and that harbors a homozygous, rare deleterious variant upon analysis of exome-sequencing data. In summary, our data suggest a distinct genetic architecture for participants with autism and co-occurring intellectual disability and that this architecture could involve a role for recessively inherited loci for this autism subgroup.     

Clinical Characteristics of Children with Autism Spectrum Disorder and Co-Occurring Epilepsy

Objectives

To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population.

Methods

Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy.

Results

The average prevalence of epilepsy in children with ASD 2–17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001).

Conclusion

This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy.     

Early Mortality and Primary Causes of Death in Mothers of Children with Intellectual Disability or Autism Spectrum Disorder: A Retrospective Cohort Study

Introduction

Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers.

Methods

The study population comprised all mothers of live-born children in Western Australia from 1983–2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers.

Results and Discussion

During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed.

Conclusion

Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers'' longevity.     

Non-Specialist Psychosocial Interventions for Children and Adolescents with Intellectual Disability or Lower-Functioning Autism Spectrum Disorders: A Systematic Review

Background

The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator.

Methods and Findings

We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies'' potential for performance bias and that few were conducted in lower- and middle-income countries.

Conclusions

The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders.

Protocol Registration

PROSPERO CRD42012002641 Please see later in the article for the Editors'' Summary     

Reduced Personal Space in Individuals with Autism Spectrum Disorder

Maintaining an appropriate distance from others is important for establishing effective communication and good interpersonal relations. Autism spectrum disorder (ASD) is a developmental disorder associated with social difficulties, and it is thus worth examining whether individuals with ASD maintain typical or atypical degrees of social distance. Any atypicality of social distancing may impact daily social interactions. We measured the preferred distances when individuals with ASD and typically developing (TD) individuals approached other people (a male experimenter) and objects (a coat rack with clothes) or when other people approached them. Individuals with ASD showed reduced interpersonal distances compared to TD individuals. The same tendency was found when participants judged their preferred distance from objects. In addition, when being approached by other people, both individuals with ASD and TD individuals maintained larger interpersonal distances when there was eye contact, compared to no eye contact. These results suggest that individuals with ASD have a relatively small personal space, and that this atypicality exists not only for persons but also for objects.     

Auditory Processing in High-Functioning Adolescents with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder including abnormalities in perceptual processing. We measure perception in a battery of tests across speech (filtering, phoneme categorization, multisensory integration) and music (pitch memory, meter categorization, harmonic priming). We found that compared to controls, the ASD group showed poorer filtering, less audio-visual integration, less specialization for native phonemic and metrical categories, and a higher instance of absolute pitch. No group differences were found in harmonic priming. Our results are discussed in a developmental framework where culture-specific knowledge acquired early compared to late in development is most impaired, perhaps because of early-accelerated brain growth in ASD. These results suggest that early auditory remediation is needed for good communication and social functioning.     

SHANK1 Deletions in Males with Autism Spectrum Disorder

Recent studies have highlighted the involvement of rare (<1% frequency) copy-number variations and point mutations in the genetic etiology of autism spectrum disorder (ASD); these variants particularly affect genes involved in the neuronal synaptic complex. The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal synapses. Although SHANK2 and SHANK3 mutations have been implicated in ASD and intellectual disability, the involvement of SHANK1 is unknown. Here, we assess microarray data from 1,158 Canadian and 456 European individuals with ASD to discover microdeletions at the SHANK1 locus on chromosome 19. We identify a hemizygous SHANK1 deletion that segregates in a four-generation family in which male carriers--but not female carriers--have ASD with higher functioning. A de novo SHANK1 deletion was also detected in an unrelated male individual with ASD with higher functioning, and no equivalent SHANK1 mutations were found in >15,000 controls (p = 0.009). The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism. The data are also informative for clinical-genetics interpretations of both inherited and sporadic forms of ASD involving SHANK1.     

Vocal Identity Recognition in Autism Spectrum Disorder

Voices can convey information about a speaker. When forming an abstract representation of a speaker, it is important to extract relevant features from acoustic signals that are invariant to the modulation of these signals. This study investigated the way in which individuals with autism spectrum disorder (ASD) recognize and memorize vocal identity. The ASD group and control group performed similarly in a task when asked to choose the name of the newly-learned speaker based on his or her voice, and the ASD group outperformed the control group in a subsequent familiarity test when asked to discriminate the previously trained voices and untrained voices. These findings suggest that individuals with ASD recognized and memorized voices as well as the neurotypical individuals did, but they categorized voices in a different way: individuals with ASD categorized voices quantitatively based on the exact acoustic features, while neurotypical individuals categorized voices qualitatively based on the acoustic patterns correlated to the speakers'' physical and mental properties.     

Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are now recognized as a core symptom in autism spectrum disorder (ASD). Our ability to perceive and interact with the external world is rooted in sensory processing. For example, listening to a conversation entails processing the auditory cues coming from the speaker (speech content, prosody, syntax) as well as the associated visual information (facial expressions, gestures). Collectively, the “integration” of these multisensory (i.e., combined audiovisual) pieces of information results in better comprehension. Such multisensory integration has been shown to be strongly dependent upon the temporal relationship of the paired stimuli. Thus, stimuli that occur in close temporal proximity are highly likely to result in behavioral and perceptual benefits – gains believed to be reflective of the perceptual system''s judgment of the likelihood that these two stimuli came from the same source. Changes in this temporal integration are expected to strongly alter perceptual processes, and are likely to diminish the ability to accurately perceive and interact with our world. Here, a battery of tasks designed to characterize various aspects of sensory and multisensory temporal processing in children with ASD is described. In addition to its utility in autism, this battery has great potential for characterizing changes in sensory function in other clinical populations, as well as being used to examine changes in these processes across the lifespan.     

Quality of Life of Taiwanese Adults with Autism Spectrum Disorder

Background

To date, few recent studies have investigated the quality of life of adults with autism spectrum disorder (ASD). It remains unclear how individuals with ASD view their own quality of life.

Objective

The primary purpose of this study was to compare the quality of life scores among adults with ASD with those of a non-ASD control group and the Taiwanese health population reference group.

Methods

The study comprised 41 adults with ASD (M age = 26.9, SD = 5.0), and without intellectual disabilities (IQ>70). A comparison sample of 41 adults without ASD was selected by matching the age and sex of the participants with ASD. A validated measure, the Taiwanese version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF), was used. Independent t-tests were performed to examine the differences in the quality of life between groups.

Results

The highest quality of life was scored in the environment domain, followed by the physical health and psychological health domains. The lowest quality of life score was found in the social relationship domain. Adults with ASD scored significantly lower in all domains than did the non-ASD control group. Additionally, adults with ASD scored significantly lower in the physical health, psychological health, and social relationship domains than did the Taiwanese health population reference group. Comorbid psychiatric disorders, self-rated health status, and perceived happiness were correlated with quality of life among adults with ASD.

Conclusion

The preliminary findings suggest that adults with ASD need more supportive social contexts and interventions to promote their quality of life. Based on our findings, social relationship must be considered in designing and applying treatment programs for adults with ASD.     

Violations of Personal Space by Individuals with Autism Spectrum Disorder

The ability to maintain an appropriate physical distance (i.e., interpersonal distance) from others is a critical aspect of social interaction and contributes importantly to real-life social functioning. In Study 1, using parent-report data that had been acquired on a large number of individuals (ages 4–18 years) for the Autism Genetic Resource Exchange and the Simons Simplex Collection, we found that those with Autism Spectrum Disorder (ASD; n = 766) more often violated the space of others compared to their unaffected siblings (n = 766). This abnormality held equally across ASD diagnostic categories, and correlated with clinical measures of communication and social functioning. In Study 2, laboratory experiments in a sample of high-functioning adults with ASD demonstrated an altered relationship between interpersonal distance and personal space, and documented a complete absence of personal space in 3 individuals with ASD. Furthermore, anecdotal self-report from several participants confirmed that violations of social distancing conventions continue to occur in real-world interactions through adulthood. We suggest that atypical social distancing behavior offers a practical and sensitive measure of social dysfunction in ASD, and one whose psychological and neurological substrates should be further investigated.     

Massively Parallel Sequencing of Patients with Intellectual Disability,Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.     

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

The discovery of the genetic causes of syndromic autism spectrum disorders and intellectual disabilities has greatly informed our understanding of the molecular pathways critical for normal synaptic function. The top-down approaches using human phenotypes and genetics helped identify causative genes and uncovered the broad spectrum of neuropsychiatric features that can result from various mutations in the same gene. Importantly, the human studies unveiled the exquisite sensitivity of cognitive function to precise levels of many diverse proteins. Bottom-up approaches applying molecular, biochemical, and neurophysiological studies to genetic models of these disorders revealed unsuspected pathogenic mechanisms and identified potential therapeutic targets. Moreover, studies in model organisms showed that symptoms of these devastating disorders can be reversed, which brings hope that affected individuals might benefit from interventions even after symptoms set in. Scientists predict that insights gained from studying these rare syndromic disorders will have an impact on the more common nonsyndromic autism and mild cognitive deficits.It is estimated that ∼1% of the human population has an autism spectrum disorder (ASD). ASD has widely varied behavioral manifestations, severity, and comorbid conditions (hence the term “spectrum”), but those diagnosed with autism are characterized by impaired communication and reciprocal social interactions, and restricted and repetitive patterns of activities and interests (Baird et al. 2006). Approximately 70% of those diagnosed with autism also have intellectual disability (ID), and 25% have a seizure disorder (Tuchman and Rapin 2002). There is a strong genetic basis for autism, but the risk architecture is highly heterogeneous, and a large number of genes have been implicated (Abrahams and Geschwind 2008). This daunting phenotypic and etiologic complexity, shared by other major psychiatric illnesses, has slowed progress toward developing new therapies.However, autism researchers are optimistic that the possibility of substantial progress may soon be realized (Krueger and Bear 2011). First, the genes have been discovered for numerous syndromic disorders that prominently feature ASD and ID. Second, these gene mutations have been reproduced in animal models that allow detailed examination of the underlying brain pathophysiology. Third, animal research has converged on altered synaptic function as a likely basis for impaired cognition and possibly ASD. Fourth, insights gained on how synapses function differently in the face of these mutations have suggested novel therapeutic interventions validated in preclinical models and that have shown promise in preliminary human clinical trials. Fifth, the fact that ASD and ID can be diagnosed in early childhood maximizes potential benefits of therapy because it can be started at a time when the brain is most plastic. Finally, animal studies using gene reactivation or pharmacological interventions suggest that substantial improvements can be seen even when treatments begin in adulthood (Ehninger et al. 2008b). Thus, a genetic diagnosis of a developmental brain disorder need not be a “life sentence” of permanent and inexorable mental disability.The path from gene discovery to novel treatment is outlined in Figure 1. This process often begins with astute clinical observations that some patients can be distinguished by a common set of phenotypic traits, thus defining a syndrome. Molecular genetic studies can then be undertaken to test the hypothesis that the syndrome has a genetic cause. In the event that disruption of a single gene or DNA segment causes the disease (i.e., a “highly penetrant” mutation), then it is possible to create an animal model (usually a mouse) that carries the same genetic disruption. Although the effects of the genetic lesion will likely manifest differently at the behavioral level in animals and humans because of differences in the complexity of the brains, it is reasonable to postulate that disruptions in elementary neuronal functions are likely to be shared. Understanding this neuronal pathophysiology is critical for identifying potential therapeutic targets. If these targets can be validated in the animal models, then chemistry ensues to generate molecules that can engage the target and satisfy the pharmacodynamic and pharmacokinetic drug requirements. If they are shown to be safe, drug candidates may then advance to human clinical trials. There are currently clinical trials ongoing in several single-gene syndromic disorders associated with ASD and ID. Most of these target alterations in synaptic signaling.Open in a separate windowFigure 1.The promise of molecular medicine in genetically defined disorders of brain development.The notion that some ASD and associated ID represent “synapsopathies” (or “synaptopathies”) is supported by the preponderance of penetrant mutations in genes associated with synaptic structure and function. The most common single-gene mutations in ASD with ID are associated with fragile X syndrome (FMR1), tuberous sclerosis (TSC1, TSC2), neurofibromatosis (NF1), Angelman syndrome (UBE3A), Rett syndrome (MECP2), the PTEN hamartoma tumor syndrome, and Phelan-McDermid syndrome (SHANK3) (for review, see Betancur 2011). Rare mutations in the neuroligin (NLGN3, NLGN2) and neurexin (NRXN1) genes also cause autism (Jamain et al. 2003). Although this is by no means an exhaustive list of genes implicated in autism (and many await discovery), it is notable nonetheless that these highly penetrant mutations occur in genes that are critical regulators of synaptic function, and further, illuminate biochemical pathways that might be pathogenic in ASD and ID (Fig. 2).Open in a separate windowFigure 2.(A) Schematic of a neuron and axonal-dendritic synapse that depict examples of cellular localization of the various types of defects in ASD/ID. (B) A signaling pathway at the excitatory synapses that couples activity as registered by the release of glutamate to local control of protein synthesis. Disruption of the gene products indicated in the colored boxes greatly increases the risk of ASD/ID. Syndromic disorders with increased prevalence of ASD include Phelan-McDermid Syndrome (SHANK3); Noonan syndrome (RAF1, MEK1); Neurofibromatosis type 1 (NF1); Costello syndrome (H-Ras, MEK1); Cowden syndrome (PTEN); Cardio-facio-cutaneous (CFC) syndrome (MEK1/2); Tuberous sclerosis complex (TSC1/2); Fragile X syndrome (FMRP); Angelman syndrome (AS UBE3a); Rett syndrome (RTT–MeCP2); and Rubinstein-Taybi syndrome (RTS–CREB binding protein, p300). Rare, nonsyndromic ASDs include NLGN3/4 and NRXN1; ID/ASD: SHANK2.In this article, we focus on a few syndromic disorders associated with ASD and ID that are characterized by penetrant mutations in genes that have been shown in animal models to disrupt synaptic function. Our goal is to highlight the similarities and differences in these syndromes and their underlying synaptic pathophysiology. Optimal synaptic function occurs within a narrow dynamic range along many dimensions, and it is not surprising that pathophysiology occurs at the edges of these spectra. What has come as a surprise, however, is that ASD and ID appear to be common consequences of disruptive mutations that cause synaptic pathophysiology at both ends of a spectrum. In other words, both “gain-of-function” and “loss-of-function” mutations can manifest in similar ways. Insights into the pathophysiology of ASD and ID have raised the possibility of therapeutic interventions to bring synapses into a normal operating range.     

孤独症谱系障碍的遗传基础与神经机制

孤独症谱系障碍(autism spectrum disorder,ASD)是一种神经精神障碍,主要表现为社会交往障碍、交流障碍以及局限性的兴趣和重复刻板的行为模式三个主要核心症状．本文介绍了ASD的遗传基础和神经机制的最新研究进展．ASD具有较高的遗传率,且ASD个体的5-羟色胺和睾丸激素都较高．神经影像学研究发现,ASD个体的杏仁核、扣带回、梭状回、镜像神经元和前额叶等大脑区域在结构和功能上都与正常发育个体存在差异,但在个别区域激活模式的差异方向上仍存在不一致的地方．此外,功能连接的研究结果也证实了ASD个体连接不良的假设．未来的研究应该更多地着眼于如何利用这些基础研究成果为临床上提出有效的治疗和训练方式．     

Autism Spectrum Disorder Initiation by Inflammation-Facilitated Neurotoxin Transport

Autism spectrum disorders have been linked to genetics, gut microbiota dysbiosis (gut dysbiosis), neurotoxin exposures, maternal allergies or autoimmune diseases. Two barriers to ingested neurotoxin transport into the central nervous system of a fetus or child are the gastrointestinal wall of the mother or child and the blood–brain barrier of the fetus or child. Inflammation from gut dysbiosis or inflammation from a disease or other agent can increase the gastrointestinal wall and the blood–brain barrier permeabilities to enable neurotoxins to reach the brain of a fetus or child. Postnatal gut dysbiosis is a particular inflammation risk for autism spectrum disorders caused by neurotoxin transport into a child's brain. An extensive gut dysbiosis or another source of inflammation such as a disease or other agent in combination with neurotoxins, including aluminum, mercury, lead, arsenic, cadmium, arsenic, organophosphates, and neurotoxic bacterial toxins and fungal toxins resulting from the gut dysbiosis, can elevate neurotoxin levels in a fetal or child brain to cause neurodevelopmental damage and initiate an autism spectrum disorder. The neurotoxins aluminum and mercury are especially synergistic in causing neurodevelopmental damage. There are three plausible causational pathways for autism spectrum disorders. They include inflammation and neurotoxin loading into the fetal brain during the prenatal neurodevelopment period, inflammation and neurotoxin loading into the brain during the postnatal neurodevelopment period or a two-stage loading of neurotoxins into the brain during both the prenatal and postnatal neurodevelopment periods.

     

Future Prospects for Epigenetics in Autism Spectrum Disorder

Molecular Diagnosis & Therapy - Despite decades of investigation into the genetics of autism spectrum disorder (ASD), a current consensus in the field persists that ASD risk is too...     

Anticipatory Smooth Eye Movements in Autism Spectrum Disorder

Smooth pursuit eye movements are important for vision because they maintain the line of sight on targets that move smoothly within the visual field. Smooth pursuit is driven by neural representations of motion, including a surprisingly strong influence of high-level signals representing expected motion. We studied anticipatory smooth eye movements (defined as smooth eye movements in the direction of expected future motion) produced by salient visual cues in a group of high-functioning observers with Autism Spectrum Disorder (ASD), a condition that has been associated with difficulties in either generating predictions, or translating predictions into effective motor commands. Eye movements were recorded while participants pursued the motion of a disc that moved within an outline drawing of an inverted Y-shaped tube. The cue to the motion path was a visual barrier that blocked the untraveled branch (right or left) of the tube. ASD participants showed strong anticipatory smooth eye movements whose velocity was the same as that of a group of neurotypical participants. Anticipatory smooth eye movements appeared on the very first cued trial, indicating that trial-by-trial learning was not responsible for the responses. These results are significant because they show that anticipatory capacities are intact in high-functioning ASD in cases where the cue to the motion path is highly salient and unambiguous. Once the ability to generate anticipatory pursuit is demonstrated, the study of the anticipatory responses with a variety of types of cues provides a window into the perceptual or cognitive processes that underlie the interpretation of events in natural environments or social situations.