A framework for an evidence-based gene list relevant to autism spectrum disorder.

Autism spectrum disorder (ASD) is often grouped with other brain-related phenotypes into a broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers need to decide which genes to test in individuals with ASD phenotypes, which requires an understanding of the level of evidence for individual NDD genes that supports an association with ASD. Consensus is currently lacking about which NDD genes have sufficient evidence to support a relationship to ASD. Estimates of the number of genes relevant to ASD differ greatly among research groups and clinical sequencing panels, varying from a few to several hundred. This Roadmap discusses important considerations necessary to provide an evidence-based framework for the curation of NDD genes based on the level of information supporting a clinically relevant relationship between a given gene and ASD.

Genome-wide detection of tandem DNA repeats that are expanded in autism.

Tandem DNA repeats vary in the size and sequence of each unit (motif). When expanded, these tandem DNA repeats have been associated with more than 40 monogenic disorders1. Their involvement in disorders with complex genetics is largely unknown, as is the extent of their heterogeneity. Here we investigated the genome-wide characteristics of tandem repeats that had motifs with a length of 2-20 base pairs in 17,231 genomes of families containing individuals with autism spectrum disorder (ASD)2,3 and population control individuals4. We found extensive polymorphism in the size and sequence of motifs. Many of the tandem repeat loci that we detected correlated with cytogenetic fragile sites. At 2,588 loci, gene-associated expansions of tandem repeats that were rare among population control individuals were significantly more prevalent among individuals with ASD than their siblings without ASD, particularly in exons and near splice junctions, and in genes related to the development of the nervous system and cardiovascular system or muscle. Rare tandem repeat expansions had a prevalence of 23.3% in children with ASD compared with 20.7% in children without ASD, which suggests that tandem repeat expansions make a collective contribution to the risk of ASD of 2.6%. These rare tandem repeat expansions included previously undescribed ASD-linked expansions in DMPK and FXN, which are associated with neuromuscular conditions, and in previously unknown loci such as FGF14 and CACNB1. Rare tandem repeat expansions were associated with lower IQ and adaptive ability. Our results show that tandem DNA repeat expansions contribute strongly to the genetic aetiology and phenotypic complexity of ASD.

Disentangling global and domain-level adaptive behavior trajectories among children with autism spectrum disorder.

BACKGROUND: Heterogeneity in adaptive behavior abilities among people with autism spectrum disorder (ASD) is expressed not only as uneven levels of impairment across domains, but also in the developmental trajectories of adaptive skills. We studied the question of whether, after accounting for global adaptive behavior development, we find evidence of heterogeneity in the trajectories of specific domains of adaptive behavior. METHODS: A sample of 504 children with ASD was obtained by combining data from two independent natural history studies conducted in North America. We used a factor of curves model to explain growth between 36 and 138 months in Vineland Adaptive Behavior Scales, Second Edition (VABS) age equivalents as a function of domain-specific and global growth processes. RESULTS: The domain-specific trajectories in all three domains (Communication, Daily Living Skills, and Socialization) reflected impairment relative to age expectations as well as slower-than-expected growth with age, and the parameters of these trajectories were moderately-to-strongly correlated across domains. The global adaptive behavior trajectory had an initial (36-41 months of age) developmental level of about 22 age-equivalent months, and eventually slowed after initially increasing by about 6 months each year. The global trajectory accounted for the majority of variance in the domain-level processes; however, additional variance remained (14%-38%) in the domain-level intercepts, slopes, and quadratic processes. CONCLUSIONS: These results extend existing theoretical and empirical support for the hierarchical structure of adaptive behavior to include its development over time in clinical samples of children with ASD. A latent global trajectory may be sufficient to describe the growth of adaptive behavior in children with ASD; however, the remaining domain-specific variability after accounting for global adaptive behavior development allows for the possibility that differential effects of intervention on specific domains may be possible and detectable.

Longitudinal associations between early childhood irritability and adolescent depression symptoms in autistic children are mediated by peer relationships but not educational engagement.

In the general population, irritability is associated with later depression. Despite irritability being more prevalent in autistic children, the long-term sequelae are not well explored. We tested whether irritability in early childhood predicted depression symptoms in autistic adolescents, and whether associations could be explained by difficulties in peer relationships and lower educational engagement. Analyses tested the longitudinal associations between early childhood irritability (ages 3-5) and adolescent depression symptoms (age 14) in a prospective inception cohort of autistic children (N = 390), followed from early in development shortly after they received a clinical diagnosis. Mediators were measured in mid-childhood (age 10) by a combination of measures, from which latent factors for peer relationships and educational engagement were estimated. Results showed early childhood irritability was positively associated with adolescent depression symptoms, and this association remained when adjusting for baseline depression. A significant indirect pathway through peer relationships was found, which accounted for around 13% of the association between early childhood irritability and adolescent depression, suggesting peer problems may partially mediate the association between irritability and later depression. No mediation effects were found for education engagement. Results highlight the importance of early screening and intervention for co-occurring irritability and peer problems in young autistic children.

Developmental cascades between insistence on sameness behaviour and anxiety symptoms in autism spectrum disorder.

Autistic children experience high rates of anxiety. Insistence on sameness behaviour (IS) is a core feature of autism that appears correlated with anxiety severity. The objective of this study was to examine the longitudinal relations between anxiety and IS in autistic children using a developmental cascade model. A longitudinal cohort of 421 autistic children was followed between 4 and 11 years of age. Anxiety was quantified using items from the Anxiety Problems subscale of the Child Behavior Checklist; sameness behaviours were measured using the Repetitive Behavior Scale-Revised, Ritualistic/sameness subscale (both parent-report measures). Structural equation modelling was used to examine the longitudinal and directional associations between anxiety and IS at four time-points, through cross-lagged panel models (CLPM) with and without a random-intercepts component (RI-CLPM). Both the CLPM and the RI-CLPM had good fit. Significant directional associations were detected whereby elevated or increasing IS preceded elevated or increasing anxiety symptoms 1-2 years later, respectively. Stable baseline tendencies towards anxiety and IS as between-person traits (intercepts) were strongly associated (standardized estimate = 0.69, p < 0.001). The magnitude of the cross-sectional associations between anxiety and IS appeared to lessen with age. IS and anxiety symptoms in autism are closely related. They appear to be shared traits that mirror each other particularly in younger children. Increasing IS may be a sign of emerging future anxiety. Interventions that target IS to reduce or prevent anxiety amongst school-aged autistic children merit further study.

Neural mechanisms of language development in infancy.

Understanding the neural processes underpinning individual differences in early language development is of increasing interest, as it is known to vary in typical development and to be quite heterogeneous in neurodevelopmental conditions. However, few studies to date have tested whether early brain measures are indicative of the developmental trajectory of language, as opposed to language outcomes at specific ages. We combined recordings from two longitudinal studies, including typically developing infants without a family history of autism, and infants with increased likelihood of developing autism (infant-siblings) (N = 191). Electroencephalograms (EEG) were recorded at 6 months, and behavioral assessments at 6, 12, 18, 24 and 36 months of age. Using a growth curve model, we tested whether absolute EEG spectral power at 6 months was associated with concurrent language abilities, and developmental change in language between 6 and 36 months. We found evidence of an association between 6-month alpha-band power and concurrent, but not developmental change in, expressive language ability in both infant-siblings and control infants. The observed association between 6-month alpha-band power and 6-month expressive language was not moderated by group status, suggesting some continuity in neural mechanisms.

Predictors of language regression and its association with subsequent communication development in children with autism.

BACKGROUND: Language regression, broadly defined as the loss of acquired language skills in early childhood, is a distinctive feature of autism. Little is known about the factors underlying regression or the prognosis of children who exhibit regression. We examine potential predictors of language regression and test its association with language development in a prospective longitudinal sample of children with autism spectrum disorder (ASD) from diagnosis to age 10 years. METHODS: We analysed data from Pathways in ASD, a prospective longitudinal study of 421 children enrolled around the time of an autism diagnosis between 2 and 5 years. Autism Diagnostic Interview-Revised data were available for 408 children, of whom 90 (22%) were classified as having language regression. RESULTS: Demographic and other health factors including caregiver education, family income, child sex, reported seizures, and age of enrolment did not differ between children with and without language regression. Children with language regression walked earlier and attained first words sooner than those without regression. However, both groups attained phrase speech at comparable ages. Those with regression exhibited greater delays in expressive and receptive communication over the follow-up period, although this effect was attenuated when accounting for baseline differences in motor and cognitive ability. Overall, those with language regression continued to exhibit expressive but not receptive communication delay compared to those without regression. Communication trajectories were heterogeneous to age 10 years, irrespective of regression status. CONCLUSIONS: Although language regression can be alarming, our findings confirm that its occurrence does not necessarily foreshadow worse developmental outcomes relative to those without regression. Although a discrepancy in age-equivalent communication skills may persist, this can be expected to be of less practical importance with rising average levels of skills. Future studies need to account for the significant variability in language trajectories by considering factors beyond developmental regression.

Middle-childhood executive functioning mediates associations between early-childhood autism symptoms and adolescent mental health, academic and functional outcomes in autistic children.

BACKGROUND: Executive functioning (EF) varies in children with autism spectrum disorder (ASD) and is associated with clinical symptoms, academic, and adaptive functioning. Here, we examined whether middle-childhood EF mediates associations between early-childhood autism symptoms and adolescent outcomes in children with ASD. METHODS: The Pathways in ASD Cohort comprising children recruited at the time of ASD diagnosis (at 2-4 years-of-age) and followed prospectively across eight subsequent timepoints over ~10 years was used. A subset of Pathways participants (n = 250) with Behavior Rating Inventory of Executive Function (BRIEF)-Parent Form data from at least one timepoint when participants were school-aged was analyzed. A mediation framework was used to examine whether BRIEF-measured EF across age 7-10 years (middle-childhood) mediated associations between early-childhood autism symptoms (measured using the parent-report Social Responsiveness Scale across age 2-6 years) and clinical, academic, and functional outcomes, indexed at age >10-11.8 years (early-adolescence) using the Child Behavior Checklist (CBCL)-Internalizing and Externalizing Scales, Academic Performance from the Teacher's Report Form, and Vineland Adaptive Behavior Scales. Models were rerun substituting clinician-rated and teacher-rated measures, where possible. RESULTS: Mediation models indicated a significant indirect effect of middle-childhood EF on associations between early-childhood autism symptoms and externalizing behavior, academic performance, or adaptive functioning in early adolescence; kappa squared (κ2 ) effect sizes ranged from large to small. Model findings were stable across raters. Middle-childhood EF did not mediate associations between early-childhood autism symptoms and adolescent internalizing behavior. CONCLUSIONS: Among children with an ASD diagnosis, middle-childhood EF may be one pathway through which early-childhood autism symptoms influence a variety of outcomes in early-adolescence. An experimental study targeting middle-childhood EF to improve adolescent academic, emotional/behavioral, and adaptive functioning is needed to evaluate the clinical meaningfulness of these findings.

Socio-demographic disparities in receipt of clinical health care services during the COVID-19 pandemic for Canadian children with disability.

BACKGROUND: Little is known about the experience of receiving in-person and virtual clinical health care services during the COVID-19 pandemic for Canadian children with developmental disabilities and delays facing multiple layers of vulnerability (e.g., low income, low educational attainment families). We examined the relationship between socio-demographic factors and the receipt of these services (physical and mental health services) during COVID-19 for Canadian children with these conditions. METHODS: Data collected in Canada for the Global Report on Developmental Delays, Disorders and Disabilities were used. The survey: (1) was developed and disseminated in collaboration with caregivers of children with disabilities, (2) included topics such as response to the pandemic and receipt of services and supports, and (3) documented the experiences of a non-random convenience sample of caregivers of children (any age) with these conditions during and prior to the pandemic. We used four logistic regression models to assess the association between socio-demographic factors and receipt of services. RESULTS: Being a single parent, having low educational attainment (high school or less), having low income (making less than $40,000 per year), working less than full time (working part-time, working reduced hours due to COVID, retired, stay home parent or student), as well as male gender and older age of the child with disability were factors associated with decreased likelihood of receiving services. CONCLUSION: Our findings point to the need for tailoring services for families of children with disabilities, particularly low socioeconomic status families, to ensure continuity of care during public health emergencies.

The Challenges of Caregivers of Children with Autism Spectrum Disorders Comorbidity during the COVID-19 Pandemic in Serbia.

BACKGROUND: Children with Autism Spectrum Disorders (ASD) experience significantly higher prevalence of other mental disorders, which amplifies their need for overall support. The outbreak of novel coronavirus (COVID-19) resulted in restrictions and limited access to different services with great challenge for families and children with ASD. SUBJECTS AND METHODS: We used an electronic SurveyMonkey questionnaire to examine the experiences of 114 caregivers of children with ASD. We compared: (a) level of support by the child's school, changes in child behavior, and priority needs for families of ASD and ASD with comorbidities (ASD+) children, during pandemic, and (b) developmental history and diagnosis for ASD and ASD+ children before the pandemic. RESULTS: Our research shows significant behavioral difficulties in the population with ASD and ASD+ that arose in the field of altered living conditions and overall functioning during the COVID-19 pandemic. Statistically significant results comparing ASD to ASD+ children we found in area of getting additional help and support before the outbreak of the pandemic (47.1% vs 16.0%, p=0.002), as well as in worsening of sleep problems, statistically significant more common in children with ASD+ (ASD+ 47.7% vs. ASD 25.7%, p=0.046). CONCLUSIONS: Our findings can contribute to the faster development and implementation of protocols for dealing with situations such as pandemics, related to the vulnerable population of children with ASD and their caregivers.

Structural templates for imaging EEG cortical sources in infants.

Electroencephalographic (EEG) source reconstruction is a powerful approach that allows anatomical localization of electrophysiological brain activity. Algorithms used to estimate cortical sources require an anatomical model of the head and the brain, generally reconstructed using magnetic resonance imaging (MRI). When such scans are unavailable, a population average can be used for adults, but no average surface template is available for cortical source imaging in infants. To address this issue, we introduce a new series of 13 anatomical models for subjects between zero and 24 months of age. These templates are built from MRI averages and boundary element method (BEM) segmentation of head tissues available as part of the Neurodevelopmental MRI Database. Surfaces separating the pia mater, the gray matter, and the white matter were estimated using the Infant FreeSurfer pipeline. The surface of the skin as well as the outer and inner skull surfaces were extracted using a cube marching algorithm followed by Laplacian smoothing and mesh decimation. We post-processed these meshes to correct topological errors and ensure watertight meshes. Source reconstruction with these templates is demonstrated and validated using 100 high-density EEG recordings from 7-month-old infants. Hopefully, these templates will support future studies on EEG-based neuroimaging and functional connectivity in healthy infants as well as in clinical pediatric populations.

Intracranial recordings reveal ubiquitous in-phase and in-antiphase functional connectivity between homotopic brain regions in humans.

Whether neuronal populations exhibit zero-lag (in-phase or in-antiphase) functional connectivity is a fundamental question when conceptualizing communication between cell assemblies. It also has profound implications on how we assess such interactions. Given that the brain is a delayed network due to the finite conduction velocity of the electrical impulses traveling across its fibers, the existence of long-distance zero-lag functional connectivity may be considered improbable. However, in this study, using human intracranial recordings we demonstrate that most interhemispheric connectivity between homotopic cerebral regions is zero-lagged and that this type of connectivity is ubiquitous. Volume conduction can be safely discarded as a confounding factor since it is known to drop almost completely within short interelectrode distances (<20 mm) in intracranial recordings. This finding should guide future electrophysiological connectivity studies and highlight the importance of considering the role of zero-lag connectivity in our understanding of communication between cell assemblies.

Co-occurring trajectories of anxiety and insistence on sameness behaviour in autism spectrum disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) have increased susceptibility to anxiety disorders. Variation in a common ASD symptom, insistence on sameness behaviour, may predict future anxiety symptoms. AIMS: To describe the joint heterogeneous longitudinal trajectories of insistence on sameness and anxiety in children with ASD and to characterise subgroups at higher risk for anxiety. METHOD: In a longitudinal ASD cohort (n = 421), insistence on sameness behaviour was measured using the Autism Diagnostic Interview-Revised at approximately ages 3, 6 and 11 years. Anxiety was quantified at 8 time points between ages 3 and 11 years using the Child Behavior Checklist (CBCL) (parent report). Clusters of participants following similar trajectories were identified using group-based and joint trajectory modelling. RESULTS: Three insistence on sameness trajectories were identified: (a) 'low-stable' (41.7% of participants), (b) 'moderate-increasing' (52.0%) and (c) 'high-peaking' (i.e. increasing then stabilising/decreasing behaviour) (6.3%). Four anxiety trajectories were identified: (a) 'low-increasing' (51.0%), (b) 'moderate-decreasing' (16.2%), (c) 'moderate-increasing' (19.6%) and (d) 'high-stable' (13.1%). Of those assigned to the 'high-peaking' insistence on sameness trajectory, 95% jointly followed an anxiety trajectory that surpassed the threshold for clinical concern (T-score >65) by middle childhood (anxiety trajectories 3 or 4). Insistence on sameness and anxiety trajectories were similar in severity and direction for 64% of the sample; for 36%, incongruous patterns were seen (e.g. decreasing anxiety and increasing insistence on sameness). CONCLUSIONS: The concurrent assessment of insistence on sameness behaviour and anxiety in ASD may help in understanding current symptom profiles and anticipating future trajectories. High preschool insistence on sameness in particular may be associated with elevated current or future anxiety symptoms.

Ethical dimensions of translational developmental neuroscience research in autism.

BACKGROUND: Since the 1990s, increasing research has been devoted to the identification of biomarkers for autism to help attain more objective diagnosis; enable early prediction of prognosis; and guide individualized intervention options. Early studies focused on the identification of genetic variants associated with autism, but more recently, research has expanded to investigate neurodevelopmental markers. While ethicists have extensively discussed issues around advances in autism genomics, much less ethical scrutiny has focused on research on early neurodevelopment and on the interventions being developed as a result. OBJECTIVES: We summarize the current state of the science on the identification of early markers for autism and its potential clinical applications, before providing an overview of the ethical issues arising from increasing understanding of children's neurodevelopment in very early life. RESULTS: Advances in the understanding of brain and behavioral trajectories preceding later autism diagnosis raise ethical concerns around three themes: (a) New models for understanding autism; (b) Risks and benefits of early identification and intervention; and (c) Communication of early concerns to families. These ethical issues should be further investigated in research conducted in partnership with autistic people and their families. CONCLUSIONS: This paper highlights the need for ethical scrutiny of early neurodevelopmental research in autism. Scrutiny requires expertise and methods from the basic sciences and bioethics, as well as constructive collaborations among autistic people, their parents, and autism researchers to anticipate early interventions that serve the community's interests and accommodate the varied experiences and preferences of people on the spectrum and their families.

Annual Research Review: Achieving universal health coverage for young children with autism spectrum disorder in low- and middle-income countries: a review of reviews.

BACKGROUND: Autism presents with similar prevalence and core impairments in diverse populations. We conducted a scoping review of reviews to determine key barriers and innovative strategies which can contribute to attaining universal health coverage (UHC), from early detection to effective interventions for autism in low- and middle-income countries (LAMIC). METHODS: A systematic literature search of review articles was conducted. Reviews relevant to the study research question were included if they incorporated papers from LAMIC and focused on children (

Profiles and Predictors of Academic and Social School Functioning among Children with Autism Spectrum Disorder.

Objective: The purpose of the study was to identify profiles and predictors of academic and social functioning in a sample of school-age children with autism spectrum disorder.Method: The study included 178 children (88% boys, 75% Caucasian, ages 10-11) who completed a standardized measure of academic skills and whose teachers completed a related measure. Measures of both academic and social performance were used to construct profiles of school functioning. Measures of language, nonverbal IQ, autism symptom severity, behavior difficulties, and early social-communication skills between ages 3 and 4 were used to examine predictors of profile membership. Latent Profile Analysis was used to identify and describe profiles of children's academic and social school functioning. Profile membership was then regressed on each of the predictors using a series of multinomial logistic regression models. Finally, a multivariate model that included all significant predictors was built to examine the best fitting constellation of profile predictors.Results: Four profiles - reflecting variation in academic achievement, school engagement, socialization skills, pragmatic language use, and social relationships - captured the diverse school functioning outcomes of the sample. Profile membership was predicted by variation in imitation, responding to joint attention, language ability, nonverbal IQ and behavior difficulties between ages 3 and 4 years. However, in a multivariate model, only language and behavior difficulties emerged as significant predictors.Conclusions: A person-centered approach to targeted early intervention that reduces behavior difficulties and enhances social-communication and language abilities may prove especially important for the promotion of later academic and social functioning at school.

Adaptation and validation of the Genetic Counseling Outcome Scale for autism spectrum disorders and related conditions.

The genetics care pathway experienced by families affected by autism spectrum disorder (ASD) around the time of diagnosis is currently uncharacterized and potentially variable across contexts. The lack of consensus on outcome measures to capture the impact of genetic services for these families shows a gap in understanding and optimizing this genetics care pathway. The Genetic Counseling Outcome Scale (GCOS-24) is a validated outcome measure of clinical genetics services. The current study aims to adapt and validate the GCOS-24 as an outcome measure in the context routine genetic testing in ASD and related conditions. Families seen for their child's developmental evaluation for ASD and related conditions were invited to participate in a genomics cohort between 2016 and 2018. Families (n = 111) completed the mGCOS-24 (modified GCOS-24), adapted from the original GCOS-24 by clinicians working in the target population's routine care pathway. The mGCOS-24 has acceptable internal consistency (Cronbach's α = 0.84) and high test-retest reliability (ICC = 0.88). It also inversely correlates with stress as measured by Perceived Stress Scale (PSS-10) and distress, as measured by the Distress Thermometer, rs ≥ 0.39, ps < 0.001. The mGCOS-24 had adequate readability, as supported by cognitive interviews completed by a sub-sample of five mothers of a child with ASD. Together, our findings show that the mGCOS-24 has good validity for the target population. Preliminary characterization of the genetics care pathway in this population revealed remarkable variability in pre-test counseling and limited post-test counseling. The use of the mGCOS-24 as an outcome measure is useful in filling some of these gaps by offering a way to assess, and in the future, optimize the genetics care pathway for families affected by autism and related neurodevelopmental conditions.

EEG-IP: an international infant EEG data integration platform for the study of risk and resilience in autism and related conditions.

BACKGROUND: Establishing reliable predictive and diganostic biomarkers of autism would enhance early identification and facilitate targeted intervention during periods of greatest plasticity in early brain development. High impact research on biomarkers is currently limited by relatively small sample sizes and the complexity of the autism phenotype. METHODS: EEG-IP is an International Infant EEG Data Integration Platform developed to advance biomarker discovery by enhancing the large scale integration of multi-site data. Currently, this is the largest multi-site standardized dataset of infant EEG data. RESULTS: First, multi-site data from longitudinal cohort studies of infants at risk for autism was pooled in a common repository with 1382 EEG longitudinal recordings, linked behavioral data, from 432 infants between 3- to 36-months of age. Second, to address challenges of limited comparability across independent recordings, EEG-IP applied the Brain Imaging Data Structure (BIDS)-EEG standard, resulting in a harmonized, extendable, and integrated data state. Finally, the pooled and harmonized raw data was preprocessed using a common signal processing pipeline that maximizes signal isolation and minimizes data reduction. With EEG-IP, we produced a fully standardized data set, of the pooled, harmonized, and pre-processed EEG data from multiple sites. CONCLUSIONS: Implementing these integrated solutions for the first time with infant data has demonstrated success and challenges in generating a standardized multi-site data state. The challenges relate to annotation of signal sources, time, and ICA analysis during pre-processing. A number of future opportunities also emerge, including validation of analytic pipelines that can replicate existing findings and/or test novel hypotheses.

Predictors of longer-term development of expressive language in two independent longitudinal cohorts of language-delayed preschoolers with Autism Spectrum Disorder.

BACKGROUND: Studies estimate that 30% of individuals with autism are minimally verbal. Understanding what factors predict longer-term expressive development in children with language delays is critical to inform identification and treatment of those at-risk for persistent language impairments. The present study examined predictors of expressive language development in language-delayed preschoolers followed through later school-age and young adulthood. METHODS: Children using single words or less on the Autism Diagnostic Observation Schedule (ADOS) at approximately 3 years old were drawn from the Early Diagnosis (EDX) and Pathways in ASD longitudinal cohorts. Age-3 predictors of Age-19 ADOS language level were identified using Classification and Regression Trees (CART) in the EDX sample. Linear mixed models examined the effects of CART-identified predictors on Vineland expressive communication (VExp) trajectories from Age-3 to Age-19. The same linear mixed models were examined in the Pathways sample, identifying predictors of VExp from ages 3 to 10.5 years. RESULTS: Significantly delayed fine motor skills (T-score < 20) was the strongest CART predictor of Age-19 language. In the linear mixed models, time, Age-3 fine motor skills and initiation of joint attention (IJA) predicted VExp trajectories in the EDX sample, even when controlling for Age-3 visual receptive abilities. In the Pathways sample, time and Age-3 fine motor skills were significant predictors of VExp trajectories; IJA and cognitive skills were not significant predictors. CONCLUSIONS: Marked deficits in fine motor skills may be a salient proxy marker for identifying language-delayed children with ASD who are at risk for persistent language impairments. This finding adds to the literature demonstrating a relation between motor and language development in ASD. Investigating individual skill areas (e.g., fine motor and nonverbal problem-solving skills), rather than broader indices of developmental level (e.g., nonverbal IQ) may provide important cues to understanding longer-term language outcomes that can be targeted in early intervention.

Autism spectrum disorder.

Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.