A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder

Background: Exposure to ambient air pollution is widespread and may be detrimental to human brain development and a potential risk factor for Autism Spectrum Disorder (ASD). We conducted a systematic review of the human evidence on the relationship between ASD and exposure to all airborne pollutants, including particulate matter air pollutants and others (e.g. pesticides and metals).

Objective: To answer the question: “is developmental exposure to air pollution associated with ASD?”

Methods: We conducted a comprehensive search of the literature, identified relevant studies using inclusion/exclusion criteria pre-specified in our protocol (registered in PROSPERO, CRD # 42015017890), evaluated the potential risk of bias for each included study and identified an appropriate subset of studies to combine in a meta-analysis. We then rated the overall quality and strength of the evidence collectively across all air pollutants.

Results: Of 1,158 total references identified, 23 human studies met our inclusion criteria (17 case-control, 4 ecological, 2 cohort). Risk of bias was generally low across studies for most domains; study limitations were related to potential confounding and accuracy of exposure assessment methods. We rated the quality of the body of evidence across all air pollutants as “moderate.” From our meta-analysis, we found statistically significant summary odds ratios (ORs) of 1.07 (95% CI: 1.06, 1.08) per 10-μg/m3 increase in PM10 exposure (n = 6 studies) and 2.32 (95% CI: 2.15, 2.51) per 10-μg/m3 increase in PM2.5 exposure (n = 3 studies). For pollutants not included in a meta-analysis, we collectively evaluated evidence from each study in rating the strength and quality of overall evidence considering factors such as inconsistency, imprecision, and evidence of dose-response. All included studies generally showed increased risk of ASD with increasing exposure to air pollution, although not consistently across all chemical components.

Conclusion: After considering strengths and limitations of the body of research, we concluded that there is “limited evidence of toxicity” for the association between early life exposure to air pollution as a whole and diagnosis of ASD. The strongest evidence was between prenatal exposure to particulate matter and ASD. However, the small number of studies in the meta-analysis and unexplained statistical heterogeneity across the individual study estimates means that the effect could be larger or smaller (including not significant) than these studies estimate. Our research supports the need for health protective public policy to reduce exposures to harmful airborne contaminants among pregnant women and children and suggests opportunities for optimizing future research.

Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.

Summary: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.

There is a paucity of literature examining the relationship between executive and social functioning in children with autism spectrum disorder (ASD). Twenty-three school-aged children with ASD participated. Executive functioning was measured using the Developmental Neuropsychological Assessment, Second Edition and Differential Ability Scales, Second Edition, and the teacher-rated Behavior Rating of Inventory of Executive Function. Independent assessors observed children’s social functioning on the playground while children with ASD and their peers completed a survey to measure peer friendships and rejections. Overall, poorer executive functioning was associated with increased playground isolation and less engagement with peers. This suggests that metacognitive skills such as initiation, working memory, and planning and organization are associated with children’s social functioning.

Keywords: Autism spectrum disorder; Executive functioning; Social skills.

gesture, imitation, deafness, dyspraxia

Background: Autism spectrum disorder (ASD) is diagnosed more frequently in boys than girls, even when girls are equally symptomatic. Cutting-edge behavioral imaging has detected “camouflaging” in girls with ASD, wherein social behaviors appear superficially typical, complicating diagnosis. The present study explores a new kind of camouflage based on language differences. Pauses during conversation can be filled with words like UM or UH, but research suggests that these two words are pragmatically distinct (e.g., UM is used to signal longer pauses, and may correlate with greater social communicative sophistication than UH). Large-scale research suggests that women and younger people produce higher rates of UM during conversational pauses than do men and older people, who produce relatively more UH. Although it has been argued that children and adolescents with ASD use UM less often than typical peers, prior research has not included sufficient numbers of girls to examine whether sex explains this effect. Here, we explore UM vs. UH in school-aged boys and girls with ASD, and ask whether filled pauses relate to dimensional measures of autism symptom severity.

Methods: Sixty-five verbal school-aged participants with ASD (49 boys, 16 girls, IQ estimates in the average range) participated, along with a small comparison group of typically developing children (8 boys, 9 girls). Speech samples from the Autism Diagnostic Observation Schedule were orthographically transcribed and time-aligned, with filled pauses marked. Parents completed the Social Communication Questionnaire and the Vineland Adaptive Behavior Scales.

Results: Girls used UH less often than boys across both diagnostic groups. UH suppression resulted in higher UM ratios for girls than boys, and overall filled pause rates were higher for typical children than for children with ASD. Higher UM ratios correlated with better socialization in boys with ASD, but this effect was driven by increased use of UH by boys with greater symptoms.

Conclusions: Pragmatic language markers distinguish girls and boys with ASD, mirroring sex differences in the general population. One implication of this finding is that typical-sounding disfluency patterns (i.e., reduced relative UH production leading to higher UM ratios) may normalize the way girls with ASD sound relative to other children, serving as “linguistic camouflage” for a naïve listener and distinguishing them from boys with ASD. This first-of-its-kind study highlights the importance of continued commitment to understanding how sex and gender change the way that ASD manifests, and illustrates the potential of natural language to contribute to objective “behavioral imaging” diagnostics for ASD.

Keywords: Autism; Disfluency; Filled pauses; Gender differences; Language; Linguistic camouflage; Pragmatic communication; Sex differences.

Parenting children with ASD has a complex history. Given parents’ increasingly pivotal role in children’s treatment, it is critical to consider parental style and behaviours. This study (1) compares parenting style of parents of children with ASD, parents of children with anxiety disorders, and parents of typically developing (TD) children and (2) investigates contributors to parenting style within and between groups. Parents of children with anxiety had a distinct parenting style compared to ASD and TD parents. Unique relationships between child symptoms and parenting behaviours emerged across the three groups. Understanding factors that impact parenting between and within clinical groups can guide the development of interventions better tailored to support the needs of parents, particularly parents of children with ASD.

Keywords: Anxiety; Autism spectrum disorder (ASD); Parenting.

Race is associated with social relationships among typically developing children; however, studies rarely examine the impact of race on social outcomes for children with autism spectrum disorder. This study examined how race (African American, Latino, Asian, or White) in conjunction with disability status (autism spectrum disorders or typically developing) and grade (grades K-2 or 3-5) affects friendships and social networks. The sample comprises 85 children with autism spectrum disorders and 85 typically developing controls matched on race, gender, age/grade, and classroom (wherever possible). Race, disability, and grade each had an independent effect on friendship nominations, and there was an interaction among the three variables. Specifically, children with autism spectrum disorders who were African American or Latino in the upper elementary grades received fewer friendship nominations than typically developing White children in the lower elementary grades. Only the presence of autism spectrum disorders was associated with social network centrality. Our results also suggested that Latino children with autism spectrum disorders in the upper elementary grades were at the highest risk of social isolation. Implications for re-conceptualizing social skills interventions are discussed.

Keywords: autism; autism spectrum disorders; friendship; race; social network; social relationships.

Purpose: We present the first study of echolalia in deaf, signing children with autism spectrum disorder (ASD). We investigate the nature and prevalence of sign echolalia in native-signing children with ASD, the relationship between sign echolalia and receptive language, and potential modality differences between sign and speech.

Method: Seventeen deaf children with ASD and 18 typically developing (TD) deaf children were video-recorded in a series of tasks. Data were coded for type of signs produced (spontaneous, elicited, echo, or nonecho repetition). Echoes were coded as pure or partial, and timing and reduplication of echoes were coded.

Results: Seven of the 17 deaf children with ASD produced signed echoes, but none of the TD deaf children did. The echoic children had significantly lower receptive language scores than did both the nonechoic children with ASD and the TD children. Modality differences also were found in terms of the directionality, timing, and reduplication of echoes.

Conclusions: Deaf children with ASD sometimes echo signs, just as hearing children with ASD sometimes echo words, and TD deaf children and those with ASD do so at similar stages of linguistic development, when comprehension is relatively low. The sign language modality might provide a powerful new framework for analyzing the purpose and function of echolalia in deaf children with ASD.

Background: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.

Methods: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while viewing biological motion (BIO) and scrambled motion (SCR). Two fMRI contrasts were analyzed: social perception (BIO > SCR) and Default Mode Network (DMN) deactivation (fixation > BIO). Age and IQ were included as covariates of no interest in all analyses.

Results: First, the between-group analyses on BIO > SCR showed that ASD is characterized by hypoactivation in the social perception circuitry, and ASD with high or low disruptive behavior exhibited similar patterns of hypoactivation. Second, the between-group analyses on fixation > BIO showed that ASD with high disruptive behavior exhibited more restricted and less DMN deactivation, when compared to ASD with low disruptive behavior or TD. Third, the within-ASD analyses showed that (a) autism symptom severity (but not disruptive behavior) was uniquely associated with less activation in the social perception regions including the posterior superior temporal sulcus and inferior frontal gyrus; (b) disruptive behavior (but not autism symptom severity) was uniquely associated with less DMN deactivation in the medial prefrontal cortex (MPFC) and lateral parietal cortex; and (c) anxiety symptoms mediated the link between disruptive behavior and less DMN deactivation in both anterior cingulate cortex (ACC) and MPFC, while ADHD symptoms mediated the link primarily in ACC.

Conclusions: In boys with ASD, disruptive behavior has a neural basis in reduced DMN deactivation, which is distinct and separable from that of core ASD symptoms, with the latter characterized by hypoactivation in the social perception circuitry. These differential neurobiological markers may potentially serve as neural targets or predictors for interventions when treating disruptive behavior vs. core symptoms in ASD.

Keywords: ADHD; Anxiety disorders; Autism spectrum disorder; Comorbidity; Default mode network; Disruptive behavior; Neuroimaging; Oppositional defiant disorder; Social perception.

An emerging hypothesis postulates that internal noise is a key factor influencing perceptual abilities in autism spectrum disorder (ASD). Given fundamental and inescapable effects of noise on nearly all aspects of neural processing, this could be a critical abnormality with broad implications for perception, behavior, and cognition. However, this proposal has been challenged by both theoretical and empirical studies. A crucial question is whether and how internal noise limits perception in ASD, independently from other sources of perceptual inefficiency, such as the ability to filter out external noise. Here, we separately estimated internal noise and external noise filtering in ASD. In children and adolescents with and without ASD, we computationally modeled individuals’ visual orientation discrimination in the presence of varying levels of external noise. The results revealed increased internal noise and worse external noise filtering in individuals with ASD. For both factors, we also observed high inter-individual variability in ASD, with only the internal noise estimates significantly correlating with severity of ASD symptoms. We provide evidence for reduced perceptual efficiency in ASD that is due to both increased internal noise and worse external noise filtering, while highlighting internal noise as a possible contributing factor to variability in ASD symptoms.