The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.
Paternally inherited cis-regulatory structural variants are associated with autism
Access to early intensive behavioral intervention for children with autism spectrum disorder is commonly recommended. Intervention programs may include high rates of instructional trials, which may evoke escape-maintained problem behavior. Recent research on “pairing” or “rapport-building” interventions have sought to reduce the likelihood that problem behavior occurs during instruction using antecedent manipulations. The current study evaluated a structured intervention that included differential reinforcement and demand fading to increase participants’ response allocation to instructional settings without the use of physical guidance. Nine minimally verbal girls under the age of 6 years with autism spectrum disorder enrolled in the study. The protocol was effective for seven of the nine participants. One participant did not complete the protocol due to competing behavior and an additional participant did not require the intervention. Our findings suggest that the structured intervention was effective in increasing appropriate behavioral repertoires that are necessary for children with autism spectrum disorder to effectively benefit from early educational programs.
Background: Narrative abilities are linked to social impairment in autism spectrum disorder (ASD), such that reductions in words about cognitive processes (e.g., think, know) are thought to reflect underlying deficits in social cognition, including Theory of Mind. However, research suggests that typically developing (TD) boys and girls tell narratives in sex-specific ways, including differential reliance on cognitive process words. Given that most studies of narration in ASD have been conducted in predominantly male samples, it is possible that prior results showing reduced cognitive processing language in ASD may not generalize to autistic girls. To answer this question, we measured the relative frequency of two kinds of words in stories told by autistic girls and boys: nouns (words that indicate object-oriented storytelling) and cognitive process words (words like think and know that indicate mentalizing or attention to other peoples’ internal states).
Methods: One hundred two verbally fluent school-aged children [girls with ASD (N = 21) and TD (N = 19), and boys with ASD (N = 41) and TD (N = 21)] were matched on age, IQ, and maternal education. Children told a story from a sequence of pictures, and word frequencies (nouns, cognitive process words) were compared.
Results: Autistic children of both sexes consistently produced a greater number of nouns than TD controls, indicating object-focused storytelling. There were no sex differences in cognitive process word use in the TD group, but autistic girls produced significantly more cognitive process words than autistic boys, despite comparable autism symptom severity. Thus, autistic girls showed a unique narrative profile that overlapped with autistic boys and typical girls/boys. Noun use correlated significantly with parent reports of social symptom severity in all groups, but cognitive process word use correlated with social ability in boys only.
Conclusion: This study extends prior research on autistic children’s storytelling by measuring sex differences in the narratives of a relatively large, well-matched sample of children with and without ASD. Importantly, prior research showing that autistic children use fewer cognitive process words is true for boys only, while object-focused language is a sex-neutral linguistic marker of ASD. These findings suggest that sex-sensitive screening and diagnostic methods-preferably using objective metrics like natural language processing-may be helpful for identifying autistic girls, and could guide the development of future personalized treatment strategies.
Keywords: Autism spectrum disorder; Mentalizing; Narratives; Natural language processing; Sex differences; Social cognition; Storytelling; Word choice.
Autism Spectrum Disorder (ASD) is increasingly prevalent [1], but long waitlists hinder children’s access to expedient diagnosis and treatment. To begin addressing this problem, we developed an automated system to detect ASD using acoustic and text features drawn from short, unstructured conversations with naïve conversation partners (confederates). Seventy children (35 with ASD and 35 typically developing (TD)) discussed a range of generic topics (e.g., pets, family, hobbies, and sports) with confederates for approximately 5 minutes. A total of 624 features (352 acoustic + 272 text) were incorporated into a Gradient Boosting Model. To reduce dimensionality and avoid overfitting, we dropped insignificant features and applied feature reduction using Principal Component Analysis. Our final model was accurate substantially above chance levels. Predictive features were both acoustic-phonetic and lexical, from both participants and confederates. The goal of this project is to develop an automatic detection system for ASD that relies on very brief, generic, and natural conversations, which can eventually be used for ASD prescreening and triage in real-world settings such as doctor’s offices and schools.
Background: The male bias in autism spectrum disorder (ASD) diagnoses is well documented. As a result, less is known about the female ASD phenotype. Recent research suggests that conclusions drawn from predominantly male samples may not accurately capture female behavior. In this study, we explore potential sex differences in attention to social stimuli, which is generally reported to be diminished in ASD. Population-based sex differences in attention to faces have been reported, such that typically developing (TD) females attend more to social stimuli (including faces) from infancy through adulthood than TD males. It is yet unknown whether population-based sex differences in the face domain are preserved in ASD.
Methods: A dynamic, naturalistic infrared eye-tracking paradigm measured attention to social stimuli (faces) in 74 school-aged males and females with ASD (male N = 23; female N = 19) and without ASD (male N = 16; female N = 16). Two kinds of video stimuli were presented that varied in social content: rich social scenes (dyadic play between two children) and lean social scenes (parallel play by two children).
Results: Results revealed a significant 3-way interaction between sex, diagnosis, and condition after controlling for chronological and mental age. ASD females attended more to faces than ASD males in the socially lean condition. This effect was not found in the typically developing (TD) group. ASD males attended less to faces regardless of social context; however, ASD females only attended significantly less to faces compared to TD females in the socially rich condition. TD males and ASD females did not differ in their attention to faces in either condition.
Conclusions: This study has implications for how the field understands core social deficits in children with ASD, which should ideally be benchmarked against same-sex peers (male and female). Social attention in ASD females fell on a continuum-greater than their ASD male peers, but not as great as TD females. Overall, their social attention mirrored that of TD males. Improved understanding of the female social phenotype in ASD will enhance early screening and diagnostic efforts and will guide the development of sex-sensitive experimental paradigms and social interventions.
Keywords: Autism spectrum disorder; Eye gaze; Sex differences; Social attention; Social cognition.
Social impairment represents one of the most challenging core deficits of autism spectrum disorder (ASD) and greatly affects children’s school experiences; however, few evidence-based social engagement programs have been implemented and sustained in schools. This pilot study examined the implementation and sustainment of a social engagement intervention, Remaking Recess, for four elementary-aged children with ASD and four school personnel in two urban public schools. The improved peer engagement and social network inclusion outcomes suggest that Remaking Recess can be feasibly implemented in under resourced public schools with fidelity and has the potential to improve child outcomes for children with ASD.
Keywords: Autism spectrum disorder; implementation fidelity; school-based social engagement intervention.