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Background Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. Methods Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. Results Clustering revealed four subgroups. One subgroup—broad symptom worsening only (20%)—included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. Limitations Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. Conclusions Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

Adults with autism spectrum disorder (ASD) experience high rates of both unemployment and depression. Though job loss predicts increased risk of depression in the general population, studies have yet to directly examine this relationship among individuals with ASD. With the backdrop of rising unemployment due to COVID-19, we used a longitudinal design to examine whether employment changes predicted increasing depressive symptoms among young adults with ASD. Online surveys were collected from young adults with ASD at two times: just before widespread social distancing measures were adopted in the United States, and again 10 weeks later. Both time points included measurement of depressive symptoms (Beck Depression Inventory-2). At Time 2, COVID-related employment changes and the perceived impact of those changes on well-being were collected. Of the young adults who were employed at Time 1 (n=144), over one-third (37.5%) reported employment changes during the first 2 months of COVID-19. Most of this change was job loss or reductions in hours or pay ("job loss/reduction"). Controlling for Time 1 depressive symptoms, young adults who experienced job loss/reduction had significantly higher depressive symptoms at Time 2 than those without an employment change. Individuals' perceived impact of employment change also predicted depressive symptoms. These findings suggest that losing a job or experiencing reductions in hours or pay leads to worsening depressive symptoms among adults with ASD. Better supporting autistic adults in the workplace may not only decrease the likelihood of job loss, but also combat the exceedingly high rates of depression in this group. LAY SUMMARY: Though unemployment has been linked to mental health problems in the general population, this relationship is seldom considered among adults with autism. In this study, we found that adults on the autism spectrum who lost their jobs or experienced reductions in pay or hours during the first 2 months of COVID-19 had worsening depression compared to adults who did not have job changes. Our findings suggest that increasing access to employment may help alleviate poor mental health among autistic adults.

The COVID‐19 pandemic has posed unique challenges for families and caregivers, as well as for autism‐focused clinicians, who are faced with providing a thorough and accurate evaluation of children's specific needs and diagnoses in the absence of in‐person assessment tools. The shift to telehealth assessments has challenged clinicians to reconsider approaches and assumptions that underlie the diagnostic assessment process, and to adopt new ways of individualizing standard assessments according to family and child needs. Mandates for physical distancing have uncovered deficiencies in diagnostic practices for suspected autism and have illuminated biases that have posed obstacles preventing children and families from receiving the services that they truly need. This Commentary outlines several considerations for improving diagnostic practices as we move forward from the current pandemic and continue to strive to build an adaptable, sustainable, equitable, and family‐centered system of care. Lay Summary Physical distancing and the abrupt end to in‐person services for many children on the autism spectrum has forced clinicians to examine the existing challenges with autism spectrum disorder (ASD) diagnostic assessment and consider things they want to keep and things that should be changed in the years ahead. New approaches such as telehealth both alleviated and exacerbated existing disparities, and brought into stark focus the importance of equitable and timely access to family‐centered care. This commentary suggests ways of improving clinical practices related to ASD assessment to continue along this path.

Symptoms of autism spectrum disorder and attention-deficit/hyperactivity disorder often co-occur, challenging timely, and accurate diagnosis. We assessed the performance of three parent-report measures in discriminating autism spectrum disorder from attention-deficit/hyperactivity disorder without autism spectrum disorder (ADHDw/oASD) in school-age verbally fluent children. We examined the Autism Symptom Interview – School-Age and two widely used parent questionnaires: Social Responsiveness Scale – 2nd Edition and Social Communication Questionnaire – Lifetime. Receiver operating characteristic curves assessed each instrument’s performance against the best-estimate clinician Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of autism spectrum disorder or of ADHDw/oASD ( n = 74, n = 102, respectively; 6–11 years). These yielded moderate accuracies: area under the curve = 0.85, 0.79, and 0.78 for Social Communication Questionnaire – Lifetime, Autism Symptom Interview, and Social Responsiveness Scale – 2nd Edition, respectively. Area under the curve pairwise comparisons reached our statistical significance ( p w/oASD. Lay abstract We tested the ability of a short, recently developed parent interview and two widely used parent-report questionnaires to discriminate school-age verbal children with autism spectrum disorder from those with attention-deficit/hyperactivity disorder without autism spectrum disorder (ADHDw/oASD). These measures included the Autism Symptom Interview – School-Age, the Social Responsiveness Scale – 2nd Edition, and the Social Communication Questionnaire – Lifetime. The classification accuracy of all three parent screeners fell in the moderate range. Accuracy varied by instrument, and the Social Communication Questionnaire – Lifetime questionniare showed the highest accuracy. Children with autism spectrum disorder who were incorrectly classified by all parent screeners did not differ from those correctly classified in regard to demographics, intellectual abilities, nor in any specific clinical area beyond general parent concerns. These findings showed that there are valid screening options for assessing school-age verbal children with autism spectrum disorder versus ADHDw/oASD. They also underscore the need to assess multiple sources of information for increased accuracy.

Depression is a common problem for adults on the autism spectrum, but little is known about depression-related service receipt in this group. To understand depression diagnostic and treatment status better, we collected information on current depressive symptoms, depression diagnosis, and treatment status of 315 young adults with a childhood diagnosis of autism from the Simons Foundation Powering Autism Research for Knowledge registry. About two-thirds (65.4%) of the adults had been diagnosed with depression, and 46.7% currently met clinical cut-offs for depression on depressive symptoms measures. Among the currently depressed, the majority (83.0%) had a formal depression diagnosis. Despite being no more likely than males to be currently depressed, females (biological sex) were more likely to have received a depression diagnosis. As for depression treatment, 58.5% of currently depressed adults were currently being treated, and 68% had previously received treatment. Medication was the most common form of treatment, followed by individual therapy. Likelihood of receiving depression treatment was higher among those with a formal depression diagnosis and with higher levels of education. Adults reported several barriers to accessing treatment for depression, including financial and insurance issues, accessibility to appropriate care, and professionals’ lack of understanding about depression in autism. Lay abstract Depression is common among adults on the autism spectrum, but little is known about the extent to which these adults living in the community access diagnostic and treatment services for depression. To address this gap, we surveyed 315 adults on the autism spectrum on depression symptoms, diagnosis, and services. About half of the sample had scores on standard depression measures that suggested they were currently depressed ( n = 147, 46.7%). Among the currently depressed, most of them had received a depression diagnosis from a professional. Depressed females were about 3.5 times more likely than depressed males to have a depression diagnosis. More than half of the currently depressed adults on the autism spectrum reported receiving depression treatment at the time of the study, while about two-thirds had previously received treatment. Those with a depression diagnosis were more likely to have received treatment, and those who had some education beyond high school were more likely to be currently receiving treatment. Financial and insurance issues were the most common barriers that adults reported in accessing treatment for depression.

This study examined COVID-19-related distress among adults with autism spectrum disorder and its associations with demographic and mental health information. A sample of 275 adults (ages 18–35) in the United States, all capable of providing self-reports, was recruited from a large national registry. Adults completed online surveys of mental health symptoms just before COVID-19 was declared a pandemic. Two months later, they completed the same surveys of mental health symptoms, and also reported about distress they had experienced as a result of the COVID-19 pandemic. Nearly two-thirds (65.9%) endorsed some form of COVID-related distress with a little over half reporting any individual form of distress. Although depressive and anxiety symptoms did not change from Time 1 to Time 2 on average, higher levels of COVID-related distress was associated with an increase in depressive and anxiety symptoms between Time 1 and Time 2. In addition, women and those who reported higher anxiety symptoms before the pandemic were more likely to report some form of COVID-related distress. The findings suggest that as this global crisis continues to unfold, it will be critical to ensure that adults with autism spectrum disorder who were experiencing mental health challenges prior to the pandemic receive appropriate monitoring. Lay abstract This study used data collected from 275 adults in the United States with autism spectrum disorder both before the pandemic and then 10 weeks into the pandemic to assess COVID-19-related distress and its impact. Two-thirds of those surveyed reported some type of distress related to the pandemic (i.e. difficulty coping or negative impact on emotional and mental health). While there were no changes in depressive and anxiety symptoms from prior to COVID-19 to 10 week later in the group as a whole, self-reported distress predicted increases in both anxiety and depression across the two timepoints. Furthermore, adults with higher levels of anxiety prior to the pandemic were more likely to report distress, and women were more likely to report a negative impact of the pandemic on their emotional and mental health. Findings highlight the importance of monitoring with adults with autism spectrum disorder to assess their need for mental health support, and providing ongoing support to those who already experience anxiety even before the pandemic.

Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10-7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

Children with autism spectrum disorder (ASD) have varying degrees of language impairment across multiple domains, which may include deficits in syntactic, pragmatic, and/or semantic skills. The heterogeneity of language profiles within ASD, coupled with the limited scope of existing standardized language measures, makes a comprehensive assessment of language impairments in ASD challenging. The Observation of Spontaneous Expressive Language (OSEL) is a new measure developed to capture children's spontaneous use of language in a naturalistic setting. The current study used the OSEL to examine the patterns of spontaneous expressive language abilities of 87 clinically ascertained children with ASD from 2 to 12 years. As expected, children with ASD were significantly more impaired in their spontaneous use of language compared to typically developing peers. Syntax and narrative skills continued to increase with age from toddler to elementary school years in cross-sectional comparisons. Pragmatic skills improved form toddler to preschool years but remained stable from preschool to elementary school years. Preliminary data also demonstrated significant improvements in OSEL syntax scores over time for a subset of children followed longitudinally (n = 8). Children with ASD consistently showed more impairments in spontaneous expressive language captured on the OSEL compared to language skills measured by other more structured standardized assessments, despite moderate convergent validity among those measures. Results suggest that impairments in the spontaneous and functional use of expressive language persist into middle childhood for many children with ASD, and a comprehensive assessment approach can lead to more precisely targeted treatment addressing specific language profiles. LAY SUMMARY: This study aimed to examine the variable language profiles in children with ASD. Children with ASD were shown to have impairments in the structure, meaning, and social use of language. These challenges were captured best by a measure that was created to assess the spontaneous use of language in a naturalistic environment. The results of this study emphasize the importance of a comprehensive assessment of language in ASD to inform treatment. Autism Res 2021, 14: 720-732. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

There is lack of consensus in the literature regarding sex differences in social outcomes for individuals on the autism spectrum. Furthermore, little research has focused on the social experiences of high school students with autism spectrum disorder (ASD) during the school day. Using a large racially/ethnically diverse sample of high school students with ASD receiving special education services (n = 547; 76 females, 471 males), we examined sex differences in social interactions of youth both during and after school. We also tested for sex differences in background and phenotypic characteristics including autism severity, IQ, adaptive behavior, and mental health. Results indicated few statistically significant differences between males and females in social interactions and phenotypic characteristics (including raw scores of autism symptom severity). However, analysis of standardized scores of autism symptoms suggested that symptom scores for females with ASD diverged more from same-sex peers in the normed sample than scores of males with ASD. Lack of sex difference in social participation for youth with ASD in this study stands in contrast to patterns of sex differences in the general population. Findings suggest that few differences between males and females with ASD, both in social participation and autism symptom severity, might result in females with ASD being more dissimilar to their same-sex peers than males with ASD. Implications of findings for understanding sex differences in ASD across the life course are discussed. LAY SUMMARY: The present study examined sex differences in social participation in a large, diverse sample of high school students with autism spectrum disorder (ASD). Males and females were very similar in their social interactions both at school and outside of school, based on reports by teachers and parents. Level of autism symptoms was also similar for males and females. However, standardized scores of autism symptoms, which take into account age and sex specific norms, suggested that females with ASD may have behaviors that are more divergent from their same-sex peers than males with ASD.

The goal of the current study was to test associations between various ASD-related behavior problems and negative peer experiences in adolescents with ASD. Data were obtained from the Bullying and School Experiences of Children with ASD Survey completed by parents in the Interactive Autism Network (IAN). The current study focused on data from 279 parents of 7th-11th graders with ASD who spent at least half of the school day in a general education setting. Logistic regression analyses found that frequent meltdowns, poor hygiene, rigid rule-keeping, and self-injury were associated with negative peer experiences. Surprisingly, repetitive behaviors and verbal tics were associated with a lower likelihood of experiencing verbal victimization.

Studies have shown that Autism Spectrum Disorder (ASD) screening and diagnostic instruments may be affected by the presence of emotional and behavior problems (EBPs). This study assessed the impact of EBPs on the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F). Participants included 290 children, 18–48 months of age, referred for ASD-related concerns. Those diagnosed with ASD had significantly lower externalizing EBPs compared to those who were not diagnosed with ASD. More externalizing symptoms and younger age were significantly predictive of an M-CHAT-R/F final score. Sensitivity and specificity was impacted by the age of the child. These results suggest that combining measures that assess EBPs and autism core symptoms may improve accuracy in this referred population.

Autistic individuals are at an increased risk for both sleep disturbances and depression. While studies in the general population and in autistic adults have drawn general links between sleep disturbances and mental health, few studies have examined the extent to which specific sleep problems may be implicated in the extremely high rates of depression among autistic adults. This study aimed to describe the patterns of sleep disturbances in autistic young adults, and their associations with depressive symptoms while controlling for relevant demographic factors. A sample of 304 legally independent adults (age 18-35 years old) with a childhood diagnosis of autism spectrum disorder self-reported on their average sleep behaviors during the past week and depressive symptoms on the Beck Depressive Inventory-II. A significant proportion (86.01%) of autistic young adults experienced at least one of the primary sleep disturbances of interest, including short total sleep time (39.59%), poor sleep efficiency (60.07%), and delayed sleep phase (36.18%). Additionally, lower sleep efficiency and delayed sleep phase were both associated with higher depressive symptoms. The associations between sleep and depressive symptoms identified in our study suggest that sleep treatments may hold potential for ameliorating depressive symptoms in autistic adults who also experience sleep problems. Further research using daily sleep diaries and objective measures of sleep behaviors, as well as longitudinal studies, are needed to understand how changes in sleep may relate to changes in depressive symptoms in autistic adults.

Objective To identify and summarize clinical practice guidelines for autism spectrum disorder (ASD) and intellectual disability (ID) for the Package of Interventions for Rehabilitation for the World Health Organization (WHO). Data Sources Academic databases, Google Scholar, guideline databases, and professional society websites were searched using the general criteria “ASD/ID” AND “rehabilitation” AND “guideline,” restricted to English-only guidelines. Study Selection Work group members independently screened titles and abstracts (1952 ASD; 1027 ID) and excluded articles if not (1) a guideline; (2) about rehabilitation; (3) published since 2008; or (4) about ASD/ID. Full-text screening (29 ASD; 5 ID) involved 3 additional exclusion criteria: (1) contained conflict of interest; (2) lacked information on strength of recommendation; or (3) failed the Appraisal of Guidelines for Research and Evaluation II instrument. Six guidelines (4 ASD: 2 on youth, 1 on adults, 1 on all ages; 2 ID: 1 on challenging behaviors, 1 on mental health) resulted. Data Extraction Work group members extracted 524 recommendations (386 ASD; 138 ID) from the guidelines including the level of evidence, diagnostic and age group, recommendation type (assessment, intervention, service), target, and valence. Data Synthesis Of the 270 intervention recommendations (212 ASD; 58 ID), only 36 for ASD and 47 for ID were empirically based. Most comprised biomedical (23%), pharmacologic (29%), and psychosocial (21%) interventions for ASD and behavioral (14%), pharmacologic (29%), and psychological (14%) interventions for ID. Intervention recommendations primarily targeted coexisting conditions (56% ASD; 93% ID), whereas core symptoms received much less attention (26% ASD). Conclusions Clinical practice guidelines reviewed for ASD and ID primarily contained recommendations based on expert opinion, with the plurality of recommendations relating to pharmacologic treatment. Vital next steps include identifying relevant interventions for inclusion in the WHO Package and continuing to conduct rigorous intervention research, particularly on core symptoms of these conditions, to extend recommendations for high-quality guidelines.

OBJECTIVE: Autism spectrum disorder (ASD) is currently considered an early-onset, neurodevelopmental condition. Follow-up studies of clinic-ascertained autism suggest that autistic symptoms typically decline with age, although symptom improvement is limited for some. To date there have been no population-based prospective studies investigating the natural history of autistic symptoms from childhood to adulthood. This study aimed to characterize the development and heterogeneity of autistic symptoms in a UK population-based cohort from childhood to age 25 years. METHOD: Data were analyzed in a prospective UK population-based cohort (ALSPAC). Trajectories were derived using five-assessments of parentrated Social Communication Disorders Checklist (SCDC) spanning ages 7-25 years. Additional measures were used to validate symptom trajectories. RESULTS: We identified three distinct SCDC trajectory classes: low (88.5%), declining (5.0%) and late‐emerging (6.5%). Both the declining and late-emerging classes were associated with child and adult ASD measures, low IQ, communication problems, peer problems and worse adult functioning, compared to the low class. Male sex was associated with an increased likelihood of being in the declining trajectory class (OR=2.84, 95% CI=2.19-3.69). This sex difference was not observed in the late-emerging group (OR=1.00, 95% CI=0.80-1.24) compared to the low class. CONCLUSIONS: ASD symptom levels emerged early and tended to decline across development although impairment was still present in adulthood for some. For others, autistic symptoms emerged across adolescence and adulthood. This challenges our current understanding that ASD symptoms inevitably first manifest early in development.

The importance of extensive genetic testing of autism spectrum disorder (ASD) cases has been demonstrated repeatedly in research settings but such testing in clinical settings remains sporadic. Determining which individuals should be prioritized for expensive tests remains a challenge. Several guidelines have been released relating to clinical genetic evaluations and testing in the context of ASD and these guidelines may be informed by the results of genetic testing in large research cohorts. The current study summarizes findings from over 2,000 individuals with ASD who received genetic testing, including microarray and exome testing, through the Simons Simplex Consortium. A returnable genetic result is identified in 10% of cases, however, this yield increases based on four readily accessible phenotypes: female sex and the presence of intellectual disability, seizures or delayed walking. Combinations of these factors increase return rate further, with some combinations yielding a return rate over 50%. In conclusion, these four phenotypes provide a simple approach to prioritize genetic testing in a clinical setting and inform future clinical guidelines. Providing a systematic approach to decisions about who to test removes barriers for, and therefore decrease disparities in, reimbursable genetic testing for individuals diagnosed with ASD.

Objective Social communication deficits associated with autism spectrum disorder (ASD) are commonly represented as a single behavioral domain. However, increased precision of measurement of social communication is needed to promote more nuanced phenotyping, both within the autism spectrum and across diagnostic boundaries. Method A large sample (N = 1,470) of 4- to 10-year-old children was aggregated from across 4 data sources, and then randomly split into testing and validation samples. A total of 57 selected social communication items from 3 widely used autism symptom measures (the Autism Diagnostic Observation Scale [ADOS], Autism Diagnostic Interview−Revised [ADI-R], and Social Responsiveness Scale [SRS]) were analyzed in the multi-trait/multi-method factor analysis framework. The selected model was then confirmed with the validation sample. Results The 4−substantive factor model, with 3 orthogonal method factors, was selected using the testing sample based on fit indices and then confirmed with the validation sample. Two of the factors, “Basic Social Communication Skills” and “Interaction Quality,” were similar to those identified in a previous analysis of the ADOS, Module 3. Two additional factors, “Peer Interaction and Modification of Behavior” and “Social Initiation and Affiliation,” also emerged. Factor scores showed nominal correlations with age and verbal IQ. Conclusion Identification of subdimensions could inform the creation of better conceptual models of social communication impairments, including mapping of how the cascading effects of social communication deficits unfold in ASD versus other disorders. Especially if extended to include both older and younger age cohorts and individuals with more varying developmental levels, these efforts could inform phenotype-based exploration for biological and genetic mechanisms by pinpointing specific mechanisms that contribute to various types of social communication deficits.

Machine learning (ML) models have demonstrated the power of utilizing clinical instruments to provide tools for domain experts in gaining additional insights toward complex clinical diagnoses. In this context these tools desire two additional properties: interpretability, being able to audit and understand the decision function, and robustness, being able to assign the correct label in spite of missing or noisy inputs. This work formulates diagnostic classification as a decision-making process and utilizes Q-learning to build classifiers that meet the aforementioned desired criteria. As an exemplary task, we simulate the process of differentiating Autism Spectrum Disorder from Attention Deficit-Hyperactivity Disorder in verbal school aged children. This application highlights how reinforcement learning frameworks can be utilized to train more robust classifiers by jointly learning to maximize diagnostic accuracy while minimizing the amount of information required.

BACKGROUND: Recent large-scale initiatives have led to systematically collected phenotypic data for several rare genetic conditions implicated in autism spectrum disorder (ASD). The onset of developmentally expected skills (e.g. walking, talking) serve as readily quantifiable aspects of the behavioral phenotype. This study’s aims were: (a) describe the distribution of ages of attainment of gross motor and expressive language milestones in several rare genetic conditions, and (b) characterize the likelihood of delays in these conditions compared with idiopathic ASD. METHODS: Participants aged 3 years and older were drawn from two Simons Foundation Autism Research Initiative registries that employed consistent phenotyping protocols. Inclusion criteria were a confirmed genetic diagnosis of one of 16 genetic conditions (Simons Searchlight) or absence of known pathogenic genetic findings in individuals with ASD (SPARK). Parent-reported age of acquisition of three gross motor and two expressive language milestones was described and categorized as on-time or delayed, relative to normative expectations. RESULTS: Developmental milestone profiles of probands with genetic conditions were marked by extensive delays (including nonattainment), with highest severity in single gene conditions and more delays than idiopathic ASD in motor skills. Compared with idiopathic ASD, the median odds of delay among the genetic groups were higher by 8.3 times (IQR 5.8–16.3) for sitting, 12.4 times (IQR 5.3–19.5) for crawling, 26.8 times (IQR 7.7–41.1) for walking, 2.7 times (IQR 1.7–5.5) for single words, and 5.7 times (IQR 2.7–18.3) for combined words. CONCLUSIONS: Delays in developmental milestones, particularly in gross motor skills, are frequent and may be among the earliest indicators of differentially affected developmental processes in specific genetically defined conditions associated with ASD, as compared with those with clinical diagnoses of idiopathic ASD. The possibility of different developmental pathways leading to ASD-associated phenotypes should be considered when deciding how to employ specific genetic conditions as models for ASD.

BackgroundSeveral recent initiatives have sought to better understand characteristic behaviors of rare genetic conditions associated with autism spectrum disorder (ASD). The onset of developmentally expected skills, such as walking and talking, serve as readily quantifiable aspects of the behavioral phenotype. The goals of this study were to describe attainment of major motor and language milestones in genetic conditions implicated in the etiology of ASD and other neurodevelopmental disorders and to compare those phenotypes to idiopathic ASD.MethodsParticipants ages 3 years and older were drawn from two Simons Foundation Autism Research Initiative-funded registries with consistent phenotyping protocols. Inclusion criteria consisted of a confirmed genetic diagnosis for one of 16 specific genetic conditions (Simons Searchlight), and absence of pathogenic genetic findings in idiopathic ASD controls (SPARK). Parent-reported age of acquisition of three motor and two language milestones was described and quantified as on-time or delayed relative to normative expectations.ResultsDelay was more common among participants with rare genetic conditions than idiopathic ASD for all milestones. Compared to the idiopathic ASD group, the median odds of delay among the genetic groups were 8.3 times (IQR 5.8-16.3) higher for sitting, 12.4 times (IQR 5.3-19.5) higher for crawling, 26.8 times (IQR 7.7-41.1) higher for walking, 2.7 times (IQR 1.7-5.5) higher for single words, and 5.7 times (IQR 2.8-18.3) higher for combined words.ConclusionDelays in major developmental milestones, particularly in motor skills, may be among the earliest clues that developmental processes may be differentially affected in specific genetically defined conditions versus a behaviorally defined disorder such as idiopathic ASD.

Currently available treatments for depression show limited effectiveness in adults with autism spectrum disorders (ASD) based on measures of symptom changes and clinician impressions. Perceived helpfulness is another metric that has been found to be useful for understanding treatment outcomes in the general population, but it has not yet been explored in adults with ASD. Thus, the current study collected online survey data to examine patient-perceived treatment helpfulness in a sample of 144 adults with ASD who reported that they were currently receiving community-based treatment for depression. Findings indicate that while there was variability in the levels of perceived helpfulness for both medication and individual therapy, most adults with ASD perceived treatment to be at least moderately helpful. Notably, adults with ASD reported having been in treatment for a prolonged duration (5 to 6 years). Ordinal logistic regression models showed that adults with more depressive symptoms perceived treatments to be less helpful (i.e., medications: odds ratio [OR] = 0.92, 95% confidence interval[CI] = 0.89-0.95; individual therapy: OR = 0.95, 95% CI = 0.92-0.99). Moreover, women perceived medication as more helpful than men (OR = 2.33, 95% CI = 1.13-4.82). Other individual (i.e., age, race, education level) and treatment (i.e., treatment length, concurrent treatment) characteristics were not significantly associated with perceived helpfulness. These findings suggest that future studies may want to use perceived helpfulness, in addition to traditionally used objective outcomes, to understand patients' treatment experience and evaluate depression treatments for adults with ASD. LAY SUMMARY: Adults with autism are much more likely to be depressed than those without autism; therefore, effective depression treatments are necessary to improve mental health outcomes in this group. This online survey study found that most adults with autism felt that the depression treatments they were receiving in the community (i.e., medication and individual therapy) were helpful. Females and those with fewer symptoms of depression felt treatments were more helpful compared with males and those with more symptoms of depression. Our findings suggest that when examining whether treatments for depression are effective, it may be important to measure adults' feelings about the helpfulness of the treatments in addition to measuring changes in symptoms of depression.

BackgroundDelayed walking is common in intellectual disability (ID) but may be less common when ID occurs with autism spectrum disorder (ASD). Previous studies examining this were limited by reliance on clinical samples and exclusion of children with severe motor deficits.ObjectiveTo examine in a population-based sample if age of walking is differentially related to intellectual ability in children with ASD versus other neurodevelopmental disorders (NDD).MethodsParticipants were from the nested Autism Birth Cohort Study of the Norwegian Mother, Father and Child Cohort Study (MoBa). Cox proportional hazards regression assessed if diagnosis (ASD n=212 vs. NDD n=354), continuous nonverbal IQ, and their interaction, were associated with continuous age of walking.ResultsThe relationship between nonverbal IQ and age of walking was stronger for NDD than for ASD (Group×nonverbal IQ interaction, χ2 =13.93, p=.0002). This interaction was characterized by a 21% decrease in the likelihood of walking onset at any given time during the observation period per 10-point decrease in nonverbal IQ (hazard ratio=0.79, 95% CI: 0.78-0.85) in the NDD group compared to 8% (hazard ratio=0.92, 95% CI: 0.86-0.98) in the ASD group.ConclusionsThe finding that age of walking is less strongly related to low intellectual ability in children with ASD than in children without other NDDs supports the hypothesis that ID in ASD may result from heterogeneous developmental pathways. Late walking may be a useful stratification variable in etiological research focused on ASD and other NDDs.

Expressive language impairment is one of the most frequently associated clinical features of 16p11.2 copy number variations (CNV). However, our understanding of the language profiles of individuals with 16p11.2 CNVs is still limited. This study builds upon previous work in the Simons Variation in Individuals Project (VIP, now known as Simons Searchlight), to characterize language abilities in 16p11.2 deletion and duplication carriers using comprehensive assessments. Participants included 110 clinically ascertained children and family members (i.e., siblings and cousins) with 16p11.2 BP4-BP5 deletion and 58 with 16p11.2 BP4-BP5 duplication between the ages of 2-23 years, most of whom were verbal. Regression analyses were performed to quantify variation in language abilities in the presence of the 16p11.2 deletion and duplication, both with and without autism spectrum disorder (ASD) and cognitive deficit. Difficulties in pragmatic skills were equally prevalent in verbal individuals in both deletion and duplication groups. NVIQ had moderate quantifiable effects on language scores in syntax and semantics/pragmatics (a decrease of less than 1 SD) for both groups. Overall, language impairments persisted even after controlling for ASD diagnosis and cognitive deficit. Language impairment is one of the core clinical features of individuals with 16p11.2 CNVs even in the absence of ASD and cognitive deficit. Results highlight the need for more comprehensive and rigorous assessment of language impairments to maximize outcomes in carriers of 16p11.2 CNVs.

In "The Need for a Clinically Useful Schema of Social Communication," Blank etal. present an observation and coding method (The Initiating, Responding, Expectancy Violations [IREV] schema) for identifying "expectancy violations (EVs)," which may signal clinically significant departures from normal social communication behavior (eg, in individuals with autism spectrum disorder [ASD]).1 The authors point out that "historically, observation of a patient's (social communication) has not been part of the routine psychiatric mental status examination," and argue that this is an important missed opportunity for clinicians. Several direct observation methods exist for identifying and/or monitoring changes in social communication deficits associated with ASD.2 Despite their established diagnostic validity, it remains true that these measures used in isolation will result in a relatively high rate of "false positives"-usually comprising children who are better described with other diagnoses (eg, intellectual disability, language disorder, attention-deficit/hyperactivity disorder [ADHD]).2 This underscores the critical importance of context when interpreting observed social communication deficits.

BackgroundConcerns have been raised that scores on standard measures of autism spectrum disorder (ASD) symptoms may differ as a function of sex. However, these findings are hindered by small female samples studied thus far. The current study evaluated if, after accounting for age, IQ, and language level, sex affects ASD severity estimates from diagnostic measures among children with ASD.MethodsData were obtained from eight sources comprising 27 sites. Linear mixed-effects models, including a random effect for site, were fit for 10 outcomes (Autism Diagnostic Observation Schedule [ADOS] domain-level calibrated severity scores, Autism Diagnostic Interview-Revised [ADI-R] raw scores by age-based algorithm, and raw scores from the two indices on the Social Responsiveness Scale [SRS]). Sex was added to the models after controlling for age, NVIQ, and an indicator for language level.ResultsSex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES]&nbsp

The parental report-based Autism Diagnostic Interview-Revised (ADI-R) and the clinician observation-based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS-2 and ADI-R toddler algorithms in a more broadly based sample of 679 toddlers (age 35–47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent-reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well-balanced sensitivity and specificity. The ADI-R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI-R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve ≥ 0.85), contributing additively to their prediction. On the ADI-R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report-based instruments such as the ADI-R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI-R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017, 10: 1672–1686. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Research studies using existing samples of individuals with autism spectrum disorders have identified differences in symptoms between males and females. Differences are typically reported in school age and adolescence, with similarities in symptom presentation at earlier ages. However, existing studies on sex differences are significantly limited, making it challenging to discern if, how, and at what point in development females with autism spectrum disorder actually exhibit a different behavioral presentation than males. The purpose of this study was to gather impressions from a large group of clinicians to isolate specific areas for future study of sex differences. Clinicians were surveyed about their opinions and perceptions of symptom severity in females, as compared to males, at different points during development. They were also asked to provide open-ended responses about female symptom presentation. Consistent with previous literature, clinicians noted more sex-related differences in restricted and repetitive behaviors and fewer differences for social communication features. Differences were most commonly observed in school age and adolescence, suggesting this time period as a critical and particularly vulnerable window for females with autism spectrum disorder. The results are discussed in the context of other male/female differences across development so that more targeted investigations of autism spectrum disorder sex differences across development.

Perceived social support (PSS) has been related to physical and mental well-being in typically developing individuals, but systematic characterizations of PSS in autism spectrum disorder (ASD) are limited. We compared self-report ratings of the multidimensional scale of PSS (MSPSS) among age- and IQ-matched groups of adults (18-58 years) with cognitively high-functioning ASD (N = 41), or attention-deficit/hyperactivity disorder (ADHD; N = 69), and neurotypical controls (NC; N = 69). Accompanying group comparisons, we used machine learning random forest (RF) analyses to explore predictors among a range of psychopathological and socio-emotional variables. Relative to both ADHD and NC, adults with ASD showed lower MSPSS ratings, specifically for the friends subscale (MSPSS-f). Across ASD and ADHD, interindividual differences in autism severity, affective empathy, symptoms of anxiety related to social interactions, hyperactivity/impulsivity, and somatization best predicted MSPSS-f. These relationships did not differ between clinical groups. While group comparisons demonstrated greater impairment in individuals with ASD, analyzing individuals' characteristics revealed cross-diagnoses similarities in regard to their MSPSS-f relationships. This is consistent with the Research Domain Criteria framework, supporting a trans-diagnostic approach as on the path toward "precision medicine." Autism Res 2017, 10: 866-877. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

International audience; We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

There is relatively little information about prospectively reported developmental milestones from caregivers of children who go on to be diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD). The current study examined rates of early skill attainment in 5-year-old children who participated in a comprehensive in-person assessment for NDDs in Hirosaki in Japan. Developmental milestone data were extracted from their Maternal and Child Health Handbook (MCHH), a booklet distributed to all pregnant women as part of universal health care. Seven hundred and twenty children underwent the assessment, among whom 455 received one or more NDD diagnoses (ASD: n = 124, non-ASD NDD: n = 331). Developmental skills were organized into four domains (motor, social interaction, communication, self-help), and the cumulative number of potential delays in each domain was calculated for each participant within three different age ranges (by 12 months, by 24 months, and by 36 months). Even by age 12 months, children with ASD/NDDs showed more potential delays across domains compared to those who received no NDD diagnosis. However, differences between those with ASD and those with non-ASD NDDs were not apparent until 24 months for social interaction and communication, and 36 months for self-help. These findings provide insights into specific behaviors that could be used to screen for ASD and other NDDs. In addition, the present study indicates the potential utility of the MCHH as a broadband screening tool to educate parents about what to look for in charting their child's early development. LAY SUMMARY: The present study examined prospectively charted developmental milestones from home-based records used as part of universal health care in 720 5-year-old children from Hirosaki, Japan. All children participated in a comprehensive evaluation to determine if they met criteria for a neurodevelopmental disorder (NDD), including autism spectrum disorder (ASD). Compared to those who received no NDD diagnosis, children with NDDs exhibited higher rates of potential delays across developmental domains, including social interaction, communication, and self-help. For some children, these delays were apparent before the age of 12 months. Differences between diagnostic groups became even more pronounced by 24 and 36 months, well before the average age of diagnosis. This suggests that home-based records can be useful tools to educate caregivers about what to look for in charting their child's early development and could assist with early screening efforts.

Children with autism spectrum disorder (ASD) present with heterogeneous levels of abilities and deficits. The identification of subgroups within a specific age range could be useful for understanding prognosis and treatment planning. We applied Hierarchical Clustering on Principal Components (HCPC) with a sample of 188 preschoolers with ASD and identified three distinct subgroups based on multiple developmental and behavioral domains. Cluster 1 was characterized by relatively high cognitive, language and adaptive abilities, and relatively low levels of social symptoms, repetitive behaviors, and sensory issues within the sample. Cluster 2 was characterized by similarly high cognitive, language and adaptive abilities compared to Cluster 1, but more severe social deficits as well as repetitive and sensory behaviors. Finally, Cluster 3 was characterized by lower cognitive, language and adaptive abilities, and more severe social, repetitive, and sensory symptoms. These findings provide insights into how considering multiple developmental and behavioral domains and core autism symptoms simultaneously can distinguish subgroups of young children with ASD and provide more comprehensive developmental profiles. Moreover, the unique profile of children in Cluster 2 highlighted the usefulness of including different measures and informants when evaluating the abilities and deficits of preschoolers with ASD and the importance of understanding the relationships among different developmental and behavioral factors in this specific population. Autism Res 2020, 13: 796-809. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism exhibit a range of abilities and deficits in different developmental and behavioral areas, making it difficult to tailor treatment and predict outcomes. We identified three distinct subgroups among 188 preschoolers with autism spectrum disorder distinguished by the combination of measures from multiple developmental and behavioral domains. The findings revealed the importance of comprehensive profiling of the child's abilities and deficits to inform subgrouping within autism.

In the present study, we examined how unstructured (e.g., spending time with friends or co-workers) and structured (e.g., attending social events at a place of workshop, sports teams) social participation changed from before to after high school for youth with autism spectrum disorders (ASD), as well as the longitudinal and concurrent relations between social participation and internalizing symptoms. Participants included 36 families of youth with ASD who were all in their last year of high school at the first time point of data collection, and who were out of high school for an average of 9 months at the second time point. Social participation and internalizing symptoms were determined using parental report. There was no average change in the amount of unstructured social participation after high school exit, although substantial individual variability was observed. Participation in structured social activities significantly declined after high school exit. Youth who had more structured social participation while in high school were significantly more likely to have gains in their unstructured social participation after high school exit. Turning to relationships between internalizing and social activities, more internalizing symptoms while youth with ASD were in high school significantly predicted increasing social isolation after high school exit (both in terms of structured and unstructured activities). Results point to the likely need for additional supports during the transition to adulthood for youth with ASD who have internalizing problems. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 663-672. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

This study reports on the initial validation of the Autism Symptom Interview (ASI), School-Age, a brief (15-20 min) phone interview derived from questions from the Autism Diagnostic Interview-Revised (ADI-R). The ASI, School-Age was administered by interviewers with minimal training to parents of children ages 5 to 12 who had all been previously identified with (or referred for assessment of) ASD or another neurodevelopmental disorder. Children then underwent a comprehensive assessment to determine a best-estimate clinical diagnosis of ASD (n = 159) or non-ASD (e.g. language disorder, intellectual disability, ADHD; n = 130). Clinicians who conducted the assessments were blind to ASI results. ROC analyses compared ASI scores to clinical diagnosis. Due to the small number of participants with non-ASD diagnoses who were classified as nonverbal (i.e. not yet using phrases on a daily basis), it was not possible to assess sensitivity and specificity of the nonverbal algorithm in this sample. The verbal algorithm yielded a sensitivity of 0.87 (95% CI = 0.81-0.92) and a specificity of 0.62 (95% CI = 0.53-0.70). When used in conjunction with the Autism Diagnostic Observation Schedule (ADOS), sensitivity and specificity were 0.82 (95% CI = 0.74-0.88) and 0.92 (95% CI = 0.86-0.96), respectively. Internal consistency and test-retest reliability were both excellent. Particularly for verbal school age children, the ASI may serve as a useful tool to more quickly ascertain or classify children with ASD for research or clinical triaging purposes. Additional data collection is underway to determine the utility of the ASI in children who are younger and/or nonverbal. Autism Res 2017, 10: 78-88. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Autism Spectrum Disorder (ASD or autism) is a heterogeneous neurodevelopmental disorder. We are now at a critical juncture in autism research where we have the knowledge base and expertise to begin to think about studies that view heterogeneity, not as 'statistical noise' that can be 'accounted for' using data-reduction techniques (such as group trajectories), but rather as 'informative variance' that can help form a more precise and dynamic picture of autism. In this Editorial we coin a new term and introduce the concept of 'chronogeneity' for the study of autism heterogeneity in relation to the dimension of time (chrono). Using examples of ongoing research and analytical advances we build the case for the potential utility of the concept of 'chronogeneity' and argue that a refined approach to the longitudinal investigation of autism (and other neurodevelopmental disorders) may move us closer to more precise and adaptive models of care for the children and youth affected by these disorders.

Diagnostic procedures for ASD (autism spectrum disorder) involve semi-naturalistic interactions between the child and a clinician. Computational methods to analyze these sessions require an end-to-end speech and language processing pipeline that go from raw audio to clinically-meaningful behavioral features. An important component of this pipeline is the ability to automatically detect who is speaking when i.e., perform child-adult speaker classification. This binary classification task is often confounded due to variability associated with the participants' speech and background conditions. Further, scarcity of training data often restricts direct application of conventional deep learning methods. In this work, we address two major sources of variability - age of the child and data source collection location - using domain adversarial learning which does not require labeled target domain data. We use two methods, generative adversarial training with inverted label loss and gradient reversal layer to learn speaker embeddings invariant to the above sources of variability, and analyze different conditions under which the proposed techniques improve over conventional learning methods. Using a large corpus of ADOS-2 (autism diagnostic observation schedule, 2nd edition) sessions, we demonstrate upto 13.45% and 6.44% relative improvements over conventional learning methods., Comment: Submitted to ICASSP 2020

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

SummaryWe present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

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Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1). Through analysis of de novo mutations in autism spectrum disorder (ASD), Sanders et al. find that small deletions, but not large deletions/duplications, contain one critical gene. Combining CNV and sequencing data, they identify 6 loci and 65 genes associated with ASD.

The Child Behavior Checklist (CBCL) has been proposed for screening of autism spectrum disorders (ASD) in clinical settings. Given the already widespread use of the CBCL, this could have great implications for clinical practice. This study examined the utility of CBCL profiles in differentiating children with ASD from children with other clinical disorders. Participants were 226 children with ASD and 163 children with attention-deficit/hyperactivity disorder, intellectual disability, language disorders, or emotional disorders, aged 2-13 years. Diagnosis was based on comprehensive clinical evaluation including well-validated diagnostic instruments for ASD and cognitive testing. Discriminative validity of CBCL profiles proposed for ASD screening was examined with area under the curve (AUC) scores, sensitivity, and specificity. The CBCL profiles showed low discriminative accuracy for ASD (AUC 0.59-0.70). Meeting cutoffs proposed for ASD was associated with general emotional/behavioral problems (EBP; mood problems/aggressive behavior), both in children with and without ASD. Cutoff adjustment depending on EBP-level was associated with improved discriminative accuracy for school-age children. However, the rate of false positives remained high in children with clinical levels of EBP. The results indicate that use of the CBCL profiles for ASD-specific screening would likely result in a large number of misclassifications. Although taking EBP-level into account was associated with improved discriminative accuracy for ASD, acceptable specificity could only be achieved for school-age children with below clinical levels of EBP. Further research should explore the potential of using the EBP adjustment strategy to improve the screening efficiency of other more ASD-specific instruments.

This article provides a selective review of advances in scientific knowledge about autism spectrum disorder (ASD), using DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) diagnostic criteria as a framework for the discussion. We review literature that prompted changes to the organization of ASD symptoms and diagnostic subtypes in DSM-IV, and we examine the rationale for new DSM-5 specifiers, modifiers, and severity ratings as well as the introduction of the diagnosis of social (pragmatic) communication disorder. Our goal is to summarize and critically consider the contribution of clinical psychology research, along with that of other disciplines, to the current conceptualization of ASD.

OBJECTIVE: Aside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). The objective of this study was to extend work in the Simons Simplex Collection by comparing the phenotypic profiles of ASD probands with or without identified de novo loss of function mutations or copy number variants in high-confidence ASD-associated genes or loci.METHOD: Analyses preemptively accounted for documented differences in sex and IQ in affected individuals with de novo mutations by matching probands with and without these genetic events on sex, IQ, and age before comparing them on multiple behavioral domains.RESULTS: Children with de novo mutations (N=112) had a greater likelihood of motor delay during early development (later age at walking), but they were less impaired on certain measures of ASD core symptoms (parent-rated social communication abnormalities and clinician-rated diagnostic certainty about ASD) in later childhood. These children also showed relative strengths in verbal and language abilities, including a smaller discrepancy between nonverbal and verbal IQ and a greater likelihood of having achieved fluent language (i.e., regular use of complex sentences).CONCLUSIONS: Children with ASD with de novo mutations may exhibit a "muted" symptom profile with respect to social communication and language deficits relative to those with ASD with no identified genetic abnormalities. Such findings suggest that examining early milestone differences and standardized testing results may be helpful in etiologic efforts, and potentially in clinical differentiation of various subtypes of ASD, but only if developmental and demographic variables are properly accounted for first.

In the present study, we examined how unstructured (e.g., spending time with friends or co-workers) and structured (e.g., attending social events at a place of workshop, sports teams) social participation changed from before to after high school for youth with autism spectrum disorders (ASD), as well as the longitudinal and concurrent relations between social participation and internalizing symptoms. Participants included 36 families of youth with ASD who were all in their last year of high school at the first time point of data collection, and who were out of high school for an average of 9 months at the second time point. Social participation and internalizing symptoms were determined using parental report. There was no average change in the amount of unstructured social participation after high school exit, although substantial individual variability was observed. Participation in structured social activities significantly declined after high school exit. Youth who had more structured social participation while in high school were significantly more likely to have gains in their unstructured social participation after high school exit. Turning to relationships between internalizing and social activities, more internalizing symptoms while youth with ASD were in high school significantly predicted increasing social isolation after high school exit (both in terms of structured and unstructured activities). Results point to the likely need for additional supports during the transition to adulthood for youth with ASD who have internalizing problems. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 663-672. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Nonverbal IQ (NVIQ) was examined in 84 individuals with autism spectrum disorder (ASD) followed from age 2 to 19. Most adults who scored in the range of intellectual disability also received scores below 70 as children, and the majority of adults with scores in the average range had scored in this range by age 3. However, within the lower ranges of ability, actual scores declined from age 2 to 19, likely due in part to limitations of appropriate tests. Use of Vineland-II daily living skills scores in place of NVIQ did not statistically improve the correspondence between age 2 and age 19 scores. Clinicians and researchers should use caution when making comparisons based on exact scores or specific ability ranges within or across individuals with ASD of different ages.

This study examines whether sensory differences can be used to classify meaningful subgroups of children with autism spectrum disorder (ASD). Caregivers of children with ASD aged 2–10 years (n = 228) completed the Short Sensory Profile. Model-based cluster analysis was used to extract sensory subtypes. The relationship of these subtypes to age, gender, autism symptom severity, and nonverbal intelligence quotient (IQ) was further explored. Four distinct sensory subtypes were identified: (a) sensory adaptive; (b) taste smell sensitive; (c) postural inattentive; and (d) generalized sensory difference. The sensory subtypes differ from each other on two dimensions: (a) the severity of reported sensory differences; and (b) the focus of differences across auditory, taste, smell, vestibular and proprioceptive domains. Examination of the clinical features of each subtype reveals two possible mechanisms of sensory disturbance in autism: (a) sensory hyperreactivity; and (b) difficulties with multisensory processing. Further, the sensory subtypes are not well explained by other variables such as age, gender, IQ, and autism symptom severity. We conclude that classification of children using sensory differences offers a promising method by which to identify phenotypes in ASD. Sensory-based phenotypes may be useful in identifying behavioral features responsive to specific interventions thereby improving intervention effectiveness. Further validation of the sensory-based phenotypes by establishing neural and physiological correlates is recommended. Autism Res 2014, 7: 322–333. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Objectives Approximately 4% of children who are deaf or hard of hearing have co-occurring autism spectrum disorder (ASD). Making an additional diagnosis of ASD in this population can be challenging, given the complexities of determining whether speech/language and social delays can be accounted for by their hearing loss, or whether these delays might be indicative of a comorbid ASD diagnosis. This exploratory study described a population of 24 children with the dual diagnosis of ASD and hearing loss. Methods Children completed a comprehensive ASD evaluation using standardized autism diagnostic instruments (Autism Diagnostic Observation Schedule, language and psychological testing). Children with permanent hearing loss who had a developmental evaluation between 2001 and 2011 and were diagnosed with an ASD based on the results of that evaluation were included. Information on communication modality, language and cognitive abilities was collected. Results The median age of diagnosis was 14 months (range 1–71) for hearing loss and 66.5 months (range 33–106) for ASD. Only 25% (n = 6) children were diagnosed with ASD ≤48 months of age and 46% by ≤6 years. Twelve (50%) children were diagnosed with ASD, 11 were diagnosed with pervasive developmental disorder not otherwise specified and 1 child had Asperger's. Most (67%) had profound degree of hearing loss. Fourteen (58%) children had received a cochlear implant, while 3 children had no amplification for hearing loss. Nine (38%) of the 24 children used speech as their mode of communication (oral communicators). Conclusions Communication delays in children who are deaf or hard of hearing are a serious matter and should not be assumed to be a direct consequence of the hearing loss. Children who received cochlear implants completed a multidisciplinary evaluation including a developmental pediatrician, which may have provided closer monitoring of speech and language progression and subsequently an earlier ASD diagnosis. Because children who are deaf or hard of hearing with ASD are challenging to evaluate, they may receive a diagnosis of ASD at older ages.

This study reports on the initial validation of the Autism Symptom Interview (ASI), School-Age, a brief (15-20 min) phone interview derived from questions from the Autism Diagnostic Interview-Revised (ADI-R). The ASI, School-Age was administered by interviewers with minimal training to parents of children ages 5 to 12 who had all been previously identified with (or referred for assessment of) ASD or another neurodevelopmental disorder. Children then underwent a comprehensive assessment to determine a best-estimate clinical diagnosis of ASD (n = 159) or non-ASD (e.g. language disorder, intellectual disability, ADHD; n = 130). Clinicians who conducted the assessments were blind to ASI results. ROC analyses compared ASI scores to clinical diagnosis. Due to the small number of participants with non-ASD diagnoses who were classified as nonverbal (i.e. not yet using phrases on a daily basis), it was not possible to assess sensitivity and specificity of the nonverbal algorithm in this sample. The verbal algorithm yielded a sensitivity of 0.87 (95% CI = 0.81-0.92) and a specificity of 0.62 (95% CI = 0.53-0.70). When used in conjunction with the Autism Diagnostic Observation Schedule (ADOS), sensitivity and specificity were 0.82 (95% CI = 0.74-0.88) and 0.92 (95% CI = 0.86-0.96), respectively. Internal consistency and test-retest reliability were both excellent. Particularly for verbal school age children, the ASI may serve as a useful tool to more quickly ascertain or classify children with ASD for research or clinical triaging purposes. Additional data collection is underway to determine the utility of the ASI in children who are younger and/or nonverbal. Autism Res 2017, 10: 78-88. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.