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Pragmatic language difficulties, including unusual filler usage, are common among children with Autism Spectrum Disorder (ASD). This study investigated "um" and "uh" usage in children with ASD and typically developing (TD) controls. We analyzed transcribed Autism Diagnostic Observation Schedule (ADOS) sessions for 182 children (117 ASD, 65 TD), aged 4 to 15. Although the groups did not differ in "uh" usage, the ASD group used fewer "ums" than the TD group. This held true after controlling for age, sex, and IQ. Within ASD, social affect and pragmatic language scores did not predict filler usage; however, structural language scores predicted "um" usage. Lower "um" rates among children with ASD may reflect problems with planning or production rather than pragmatic language.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with substantial clinical heterogeneity, especially in language and communication ability. There is a need for validated language outcome measures that show sensitivity to true change for this population. We used Natural Language Processing to analyze expressive language transcripts of 64 highly-verbal children and young adults (age: 6-23 years, mean 12.8 years; 78.1% male) with ASD to examine the validity across language sampling context and test-retest reliability of six previously validated Automated Language Measures (ALMs), including Mean Length of Utterance in Morphemes, Number of Distinct Word Roots, C-units per minute, unintelligible proportion, um rate, and repetition proportion. Three expressive language samples were collected at baseline and again 4 weeks later. These samples comprised interview tasks from the Autism Diagnostic Observation Schedule (ADOS-2) Modules 3 and 4, a conversation task, and a narration task. The influence of language sampling context on each ALM was estimated using either generalized linear mixed-effects models or generalized linear models, adjusted for age, sex, and IQ. The 4 weeks test-retest reliability was evaluated using Lin's Concordance Correlation Coefficient (CCC). The three different sampling contexts were associated with significantly (P

Limited access to screening and evaluation for autism spectrum disorder in children is a major barrier to improving outcomes for marginalized families. To identify and evaluate available digital autism spectrum disorder screening resources, we simulated web and mobile app searches by a parent concerned about their child's likelihood of autism spectrum disorder. Included digital autism spectrum disorder screening tools (a) were on Internet or mobile app; (b) were in English; (c) had a parent user inputting data; (d) assigned likelihood category to child <9 years; and (e) screened for autism spectrum disorder. Ten search terms, developed using Google Search and parent panel recommendations, were used to search web and app tools in the United States, the United Kingdom, India, Australia, and Canada using Virtual Private Networks. Results were examined for attributes likely to benefit parents in marginalized communities, such as ease of searching, language versions, and reading level. The four terms most likely to identify any tools were "autism quiz," "autism screening tool," "does my child have autism," and "autism toddler." Three out of five searches contained autism spectrum disorder screening tools, as did one of 10 links or apps. Searches identified a total of 1475 websites and 919 apps, which yielded 23 unique tools. Most tools required continuous Internet access or offered only English, and many had high reading levels. In conclusion, screening tools are available, but they are not easily found. Barriers include inaccessibility to parents with limited literacy or limited English proficiency, and frequent encounters with games, advertisements, and user fees.

Pragmatic language difficulties, including unusual filler usage, are common among children with Autism Spectrum Disorder (ASD). This study investigated 'um' and 'uh' usage in children with ASD and typically developing (TD) controls. We analyzed transcribed Autism Diagnostic Observation Schedule (ADOS) sessions for 182 children (117 ASD, 65 TD), aged 4 to 15. Although the groups did not differ in 'uh' usage, the ASD group used fewer 'ums' than the TD group. This held true after controlling for age, sex, and IQ. Within ASD, social affect and pragmatic language scores did not predict filler usage; however, structural language scores predicted 'um' usage. Lower 'um' rates among children with ASD may reflect problems with planning or production rather than pragmatic language., Author(s): Grace O. Lawley [sup.1] , Steven Bedrick [sup.2] , Heather MacFarlane [sup.3] , Jill K. Dolata [sup.4] , Alexandra C. Salem [sup.3] , Eric Fombonne [sup.3] [sup.4] Author Affiliations: [...]

Expressive language sampling (ELS) is a frequently used tool for language analysis, as it can be used across widely ranging cognitive and language abilities. ELS can also evaluate pragmatic language, including excessive self-repetition, which is challenging to assess with traditional standardized assessments. This study explored how a well-established ELS protocol can assess three types of linguistic self-repetition in three neurodevelopmental disabilities: fragile X syndrome (FXS), autism spectrum disorder (ASD), and Down syndrome (DS). We examined its ability to differentiate between these disorders, the relationships between repetitive language and other participant characteristics, and initial construct validity. We found that the groups with FXS and ASD differed significantly on each of the three repetitive language measure, and that the group with DS differed from either ASD or FXS on two. Cognitive ability was significantly related to phrase repetition in the group with ASD. When the groups were combined, there was evidence of convergent and divergent validity. This study extends previous research on ELS and supports its use as a means to characterize pragmatic language. It also provides information about the relationships between repetitive language and other phenotypic characteristics.

The SPARK cohort was established to facilitate recruitment in studies of large numbers of participants with autism spectrum disorder (ASD). Online registration requires participants to have received a lifetime professional diagnosis by health or school providers although diagnoses are not independently verified. This study was set to examine the validity of self- and caregiver-reported autism diagnoses. Electronic medical records (EMR) of 254 SPARK participants (77.6% male, age 10.7 years) were abstracted. Using two different methods, confirmation of ASD diagnosis in EMRs was obtained in 98.8% of cases. Core clinical features recorded in EMRs were typical of autism samples and showed very good agreement with SPARK cohort data, providing further evidence of the validity of clinical information in the SPARK database.

Black children with autism are diagnosed at an older age. Whether or not late detection is paralleled by differing clinical presentation is not known. We evaluated symptom profiles of 245 Black and 488 sex- and age-matched White non-Hispanic participants (82.8% male; mean age: 4.2 years) referred for ASD diagnosis. Both groups showed similar overall levels of autistic symptoms. Black children had significantly but slightly lower scores on cognitive tests and on the Vineland communication domain than White children. Groups were comparable on internalizing and externalizing co-occurring problems. Given the largely similar clinical profiles, clinical differences in initial presentation may not be a primary reason for Black/White disparities in diagnostic and services use. Limitations of a cross-sectional referred sample are acknowledged.

Recent worldwide epidemiological surveys of autism conducted in 37 countries are reviewed; the median prevalence of autism is 0.97% in 26 high-income countries. Methodological advances and remaining challenges in designing and executing surveys are discussed, including the effects on prevalence of variable case definitions and nosography, of reliance on parental reports only, case ascertainment through mainstream school surveys, innovative approaches to screen school samples more efficiently, and consideration of age in interpreting surveys. Directions for the future of autism epidemiology are discussed, including the need to systematically examine cross-cultural variation in phenotypic expression and developing surveillance programs.

The recent adaptation of a Chinese parent version of the Autism Spectrum Rating Scale showed the Modified Chinese Autism Spectrum Rating Scale to be reliable and valid for use in China. The aim of this study was to test the Modified Chinese Autism Spectrum Rating Scale for fit to the Rasch model. We analysed data from a previous study of the Modified Chinese Autism Spectrum Rating Scale which comprised 1593 non-cases and 420 children diagnosed with autism spectrum disorder. We used super items based on groups of locally dependent items and item deletion when necessary to achieve good fit to the model for each of the three subscales identified by Zhou et al. and for the full 59-item Modified Chinese Autism Spectrum Rating Scale. The resulting conversion tables enable the use of genuine unidimensional, interval level scores for the total score and three subscales. Reliability was high with Person Separation Index values ranging from 0.83 to 0.89 for the three subscales and 0.79 for the total scale. In addition, we were able to identify a full-scale version of the Autism Spectrum Rating Scale and its three subscales that are all free of differential item functioning in relation to the five person factors recorded namely age, sex, caseness, relative and city. In future studies, the Teacher version of the Modified Chinese Autism Spectrum Rating Scale needs examination with Rasch analysis.

BACKGROUND: Fear of autism has led to a decline in childhood-immunization uptake and to a resurgence of preventable infectious diseases. Identifying characteristics of parents who believe in a causal role of vaccines for autism spectrum disorder (ASD) in their child may help targeting educational activities and improve adherence to the immunization schedule. OBJECTIVES: To compare caregivers of children with ASD who agree or disagree that vaccines play an etiological role in autism for 1) socio-demographics characteristics and 2) developmental and clinical profiles of their children. METHODS: Data from 16,525 participants with ASD under age 18 were obtained from SPARK, a national research cohort started in 2016. Caregivers completed questionnaires at registration that included questions on beliefs about the etiologic role of childhood immunizations and other factors in ASD. Data were available about family socio-demographic characteristics, first symptoms of autism, developmental regression, co-occurring psychiatric disorders, seizures, and current levels of functioning. RESULTS: Participants with ASD were 80.4% male with a mean age of 8.1 years (SD = 4.1). Overall, 16.5% of caregivers endorsed immunizations as perceived causes of autism. Compared to caregivers who disagreed with vaccines as a cause for ASD, those who believed in vaccine causation came disproportionately from ethnic minority, less educated, and less wealthy backgrounds. More often their children had experienced developmental regression involving language and other skills, were diagnosed earlier, had lost skills during the second year of life, and had worse language, adaptive, and cognitive outcomes. CONCLUSION: One in six caregivers who participate in a national research cohort believe that child immunizations could be a cause of autism in their child. Parent social background (non-White, less educated) and child developmental features (regression in second year, poorer language skills, and worse adaptive outcomes) index caregivers who are more likely to harbor these beliefs and could benefit from targeted educational activities.

The SPARK cohort was established to facilitate recruitment in studies of large numbers of participants with autism spectrum disorder (ASD). Online registration requires participants to have received a lifetime professional diagnosis by health or school providers although diagnoses are not independently verified. This study was set to examine the validity of self- and caregiver-reported autism diagnoses. Electronic medical records (EMR) of 254 SPARK participants (77.6% male, age 10.7 years) were abstracted. Using two different methods, confirmation of ASD diagnosis in EMRs was obtained in 98.8% of cases. Core clinical features recorded in EMRs were typical of autism samples and showed very good agreement with SPARK cohort data, providing further evidence of the validity of clinical information in the SPARK database., Author(s): Eric Fombonne [sup.1] [sup.2] , Leigh Coppola [sup.1] , Sarah Mastel [sup.1] , Brian J. O'Roak [sup.3] Author Affiliations: (1) grid.5288.7, 0000 0000 9758 5690, Department of Psychiatry, Oregon [...]

Improving autism spectrum disorder screening and referral in primary care may reduce autism spectrum disorder disparities for Latino children. The REAL-START intervention aimed to increase primary care provider adherence to autism spectrum disorder and developmental screening guidelines, and to increase Early Intervention referral for children at developmental risk in primary care clinics serving Latinos. This quasi-experimental study enrolled six Oregon primary care clinics. Clinic staff attended one initial and three follow-up trainings. Trainings addressed screening, billing, referral, and follow-up issues specific to Latinos. Clinic leaders met with a quality improvement facilitator to review performance. Medical record review measured screening and referral at 18- and 24-month well-child visits at baseline and 3, 6, 9, and 12 months. State Early Intervention database queries assessed Early Intervention eligibility. Overall, 2224 well-child visits were assessed (39% Latino). Clinics improved rates of autism spectrum disorder screening from 70% to 94% and general developmental screening from 62% to 95%. Adherence to screening guidelines increased from 46% to 91%. Proportion of children referred to Early Intervention was unchanged, but total referrals increased and age range of referred children broadened. Time to Early Intervention evaluation was slightly shorter among screening-age children. REAL-START may improve screening and referral for autism spectrum disorder and developmental delay in Latino communities.

Black children with autism are diagnosed at an older age. Whether or not late detection is paralleled by differing clinical presentation is not known. We evaluated symptom profiles of 245 Black and 488 sex- and age-matched White non-Hispanic participants (82.8% male; mean age: 4.2 years) referred for ASD diagnosis. Both groups showed similar overall levels of autistic symptoms. Black children had significantly but slightly lower scores on cognitive tests and on the Vineland communication domain than White children. Groups were comparable on internalizing and externalizing co-occurring problems. Given the largely similar clinical profiles, clinical differences in initial presentation may not be a primary reason for Black/White disparities in diagnostic and services use. Limitations of a cross-sectional referred sample are acknowledged., Author(s): Eric Fombonne [sup.1] [sup.2] , Katharine E. Zuckerman [sup.2] [sup.3] Author Affiliations: (1) grid.5288.7, 0000 0000 9758 5690, Department of Psychiatry, Oregon Health & Science University, , Mail code: [...]

This study examined lifetime medical and psychiatric morbidity reported by caregivers of 2917 autistic adults participating in the US research cohort SPARK. Participants were 78.4% male, 47.3% had intellectual disability, and 32.1% had persistent language impairments. Childhood language disorders (59.7%), speech/articulation problems (32.8%), sleep (39.4%) and eating problems (29.4%), motor delays (22.8%) and history of seizure (15.5%) were the most frequently reported clinical features. Over two thirds (67.2%) had been diagnosed with at least one psychiatric disorder (anxiety disorders: 41.1%; ADHD: 38.7%). Compared to verbally fluent participants, those with language impairments had lower frequencies of almost all psychiatric disorders. Female sex and older age were associated with higher medical and psychiatric morbidity. [This article was written with the SPARK Consortium.]

Mobile health (mHealth) screening tools for autism are gaining in prevalence, and have benefits such as video content and direct resources linkage. However, it is unclear whether such tools will ameliorate autism inequities or will help only those already advantaged in autism care. To investigate this issue, we conducted semi-structured qualitative interviews with 18 primary care and Early Intervention/Early Childhood Special Education providers in six US states. Providers were given hypothetical scenarios in which a family presents to care with results from one of 9 mHealth autism screening tools. Providers discussed their clinical approach and assessed the tool's fit with their patient/client population. Each transcript was audio-recorded, transcribed, and coded; a phenomenological approach was used to develop key themes. 4 themes and 18 subthemes emerged. These included Clinical and business factors (e.g. scope of practice concerns and clinical efficiency), Validity and trustworthiness (e.g. familiarity, data privacy/security), Family interaction quality (e.g. supporting family advocacy, provision of information, affecting family anxiety, and emotional support), and Accessibility (e.g. English proficiency/language issues, cultural inclusivity, and literacy/educational level). Providers suggested modifications to enhance equity, such as portraying diverse families, reducing the reading level of text, and making tools shorter to better fit clinical context. Families may find information about autism online, and health care and education providers may use online tools to screen for autism. However, we do not know if online autism screening tools are easily used by families and providers. We interviewed primary care and educational providers, asking them to review results from online tools that screen for autism. Providers had concerns about how usable and accessible these tools are for diverse families and suggested changes to make tools easier to use. [ABSTRACT FROM AUTHOR]

Recent worldwide epidemiological surveys of autism conducted in 37 countries are reviewed; the median prevalence of autism is .97% in 26 high-income countries. Methodological advances and remaining challenges in designing and executing surveys are discussed, including the effects on prevalence of variable case definitions and nosography, of reliance on parental reports only, case ascertainment through mainstream school surveys, innovative approaches to screen school samples more efficiently, and consideration of age in interpreting surveys. Directions for the future of autism epidemiology are discussed, including the need to systematically examine cross-cultural variation in phenotypic expression and developing surveillance programs., Author(s): Eric Fombonne [sup.1] , Heather MacFarlane [sup.1] , Alexandra C. Salem [sup.1] Author Affiliations: (1) grid.5288.7, 0000 0000 9758 5690, Department of Psychiatry, Oregon Health & Science University, , [...]

Inconsistent findings regarding sex differences in cognition have been found in people with autism spectrum disorder (ASD). This study evaluated sex differences in cognitive-developmental functioning in a large clinical sample of young children diagnosed with ASD. The sample included children 18-68 months of age who received the Mullen Scales of Early Learning (MSEL) through Autism Treatment Network (ATN) sites from 2007 to 2013 (N = 1587, 16.7% female). In this large clinically referred sample of young children with ASD in the United States, no significant differences were found between the sexes for the MSEL Early Learning Composite (ELC) standard score, domain T Scores or age equivalents. These findings persisted when examining different age ranges, cognitive levels and domain profiles.

Validated screening and diagnostic tools for autism spectrum disorder for use in Arabic-speaking individuals are scarce. This study validated the Arabic version of the Social Communication Questionnaire. The total study sample included 206 children with autism spectrum disorder and 206 typically developing children (73.8% male; mean age: 8.5 (standard deviation = 2.6) years). The mean Social Communication Questionnaire total score was significantly higher in autism spectrum disorder children than in typically developing children (p < 0.0001). Scores on the three Social Communication Questionnaire subscales also differed significantly between the groups (p < 0.001). Of the 39 items, 37 were endorsed significantly more often in the autism spectrum disorder group. The total Social Communication Questionnaire score did not vary by age or gender. Internal consistency was excellent (alpha = 0.92). In the receiver operating characteristic analysis, the area under the curve for the total score showed excellent discrimination between autism spectrum disorder and typically developing children (area under the curve = 0.95; 95% confidence interval: 0.93-0.97). The areas under the curve for the scale subscores were 0.923 (95% confidence interval: 0.898-0.949) for the social interaction score, 0.872 (95% confidence interval: 0.838-0.905) for the communication score, and 0.856 (95% confidence interval: 0.819-0.893) for the repetitive behaviors score. The findings support the use of the Arabic Social Communication Questionnaire to successfully differentiate children with clinically diagnosed autism spectrum disorder using the established cutoff value for the English version.

The Simons Foundation Autism Research Initiative (SFARI) has launched SPARKForAutism.org, a dynamic platform that is engaging thousands of individuals with autism spectrum disorder (ASD) and connecting them to researchers. By making all data accessible, SPARK seeks to increase our understanding of ASD and accelerate new supports and treatments for ASD.

This study examined lifetime medical and psychiatric morbidity reported by caregivers of 2917 autistic adults participating in the US research cohort SPARK. Participants were 78.4% male, 47.3% had intellectual disability, and 32.1% had persistent language impairments. Childhood language disorders (59.7%), speech/articulation problems (32.8%), sleep (39.4%) and eating problems (29.4%), motor delays (22.8%) and history of seizure (15.5%) were the most frequently reported clinical features. Over two thirds (67.2%) had been diagnosed with at least one psychiatric disorder (anxiety disorders: 41.1%; ADHD: 38.7%). Compared to verbally fluent participants, those with language impairments had lower frequencies of almost all psychiatric disorders. Female sex and older age were associated with higher medical and psychiatric morbidity., Author(s): Eric Fombonne [sup.1] , LeeAnne Green Snyder [sup.2] , Amy Daniels [sup.2] , Pamela Feliciano [sup.2] , Wendy Chung [sup.2] [sup.3] , Leonard Abbeduto, Gabriella Aberbach, John Acampado, Andrea [...]

Inconsistent findings regarding sex differences in cognition have been found in people with autism spectrum disorder (ASD). This study evaluated sex differences in cognitive-developmental functioning in a large clinical sample of young children diagnosed with ASD. The sample included children 18-68 months of age who received the Mullen Scales of Early Learning (MSEL) through Autism Treatment Network (ATN) sites from 2007 to 2013 (N = 1587, 16.7% female). In this large clinically referred sample of young children with ASD in the United States, no significant differences were found between the sexes for the MSEL Early Learning Composite (ELC) standard score, domain T Scores or age equivalents. These findings persisted when examining different age ranges, cognitive levels and domain profiles., Author(s): Susanne W. Duvall [sup.1] [sup.2] , Lark Huang-Storms [sup.1] , Alison Presmanes Hill [sup.1] [sup.3] , Julianne Myers [sup.3] [sup.4] , Eric Fombonne [sup.1] [sup.2] Author Affiliations: (1) grid.5288.7, [...]

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).

BackgroundPhenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of subphenotyping of a well-characterized autism spectrum disorder (ASD) sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD.MethodsGenome-wide genotypic data of 2576 families from the Simons Simplex Collection were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study, as well as estimating heritability and evaluating allele scores for each phenotypic subgroup.ResultsAssociation analyses revealed no genome-wide significant association signal. Subphenotyping did not increase power substantially. Moreover, allele scores built from the most associated single nucleotide polymorphisms, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups.ConclusionsIn genome-wide association analysis of the Simons Simplex Collection sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of subphenotypes is not a productive path forward for discovering genetic risk variants in ASD.

Attention-deficit/hyperactive disorder (ADHD) and autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large-scale network organization among three groups of children: a group with ADHD (8-12 years, n = 20), a group with ASD (7-13 years, n = 16), and typically developing controls (TD) (8-12 years, n = 20). We apply the concept of the rich-club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich-club network phenomena and (2) outside a rich-club network phenomena. The ASD and ADHD groups had markedly different patterns of rich club and non rich-club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich-club networks. These findings were replicated using the autism brain imaging data exchange dataset with ASD (n = 85) and TD (n = 101). The ADHD group exhibited a lower generalized fractional anisotropy and functional connectivity inside the rich-club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large-scale connectivity patterns in middle childhood.

The proximal region of chromosome 15 is one of the genomic hotspots for copy number variants (CNVs). Among the rearrangements observed in this region, CNVs from the interval between the common breakpoints 1 and 2 (BP1 and BP2) have been reported cosegregating with autism spectrum disorder (ASD). Although evidence supporting an association between BP1-BP2 CNVs and autism accumulates, the magnitude of the effect of BP1-BP2 CNVs remains elusive, posing a great challenge to recurrence-risk counseling. To gain further insight into their pathogenicity for ASD, we estimated the penetrance of the BP1-BP2 CNVs for ASD as well as their effects on ASD-related phenotypes in a well-characterized ASD sample (n = 2525 families). Transmission disequilibrium test revealed significant preferential transmission only for the duplicated chromosome in probands (20T:9NT). The penetrance of the BP1-BP2 CNVs for ASD was low, conferring additional risks of 0.3% (deletion) and 0.8% (duplication). Stepwise regression analyses suggest a greater effect of the CNVs on ASD-related phenotype in males and when maternally inherited. Taken together, the results are consistent with BP1-BP2 CNVs as risk factors for autism. However, their effect is modest, more akin to that seen for common variants. To be consistent with the current American College of Medical Genetics guidelines for interpretation of postnatal CNV, the BP1-BP2 deletion and duplication CNVs would probably best be classified as variants of uncertain significance (VOUS): they appear to have an impact on risk, but one so modest that these CNVs do not merit pathogenic status.

ObjectiveChanges in autism diagnostic criteria found in DSM-5 may affect autism spectrum disorder (ASD) prevalence, research findings, diagnostic processes, and eligibility for clinical and other services. Using our published, total-population Korean prevalence data, we compute DSM-5 ASD and social communication disorder (SCD) prevalence and compare them with DSM-IV pervasive developmental disorder (PDD) prevalence estimates. We also describe individuals previously diagnosed with DSM-IV PDD when diagnoses change with DSM-5 criteria.MethodThe target population was all children from 7 to 12 years of age in a South Korean community (N = 55,266), those in regular and special education schools, and a disability registry. We used the Autism Spectrum Screening Questionnaire for systematic, multi-informant screening. Parents of screen-positive children were offered comprehensive assessments using standardized diagnostic procedures, including the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Best-estimate clinical diagnoses were made using DSM-IV PDD and DSM-5 ASD and SCD criteria.ResultsDSM-5 ASD estimated prevalence was 2.20% (95% confidence interval = 1.77-3.64). Combined DSM-5 ASD and SCD prevalence was virtually the same as DSM-IV PDD prevalence (2.64%). Most children with autistic disorder (99%), Asperger disorder (92%), and PDD-NOS (63%) met DSM-5 ASD criteria, whereas 1%, 8%, and 32%, respectively, met SCD criteria. All remaining children (2%) had other psychopathology, principally attention-deficit/hyperactivity disorder and anxiety disorder.ConclusionOur findings suggest that most individuals with a prior DSM-IV PDD meet DSM-5 diagnostic criteria for ASD and SCD. PDD, ASD or SCD; extant diagnostic criteria identify a large, clinically meaningful group of individuals and families who require evidence-based services.

BACKGROUND: Brain development follows a different trajectory in children with autism spectrum disorders (ASD) than in typically developing children. A proxy for neurodevelopment could be head circumference (HC), but studies assessing HC and its clinical correlates in ASD have been inconsistent. This study investigates HC and clinical correlates in the Simons Simplex Collection cohort. METHODS: We used a mixed linear model to estimate effects of covariates and the deviation from the expected HC given parental HC (genetic deviation). After excluding individuals with incomplete data, 7225 individuals in 1891 families remained for analysis. We examined the relationship between HC/genetic deviation of HC and clinical parameters. RESULTS: Gender, age, height, weight, genetic ancestry, and ASD status were significant predictors of HC (estimate of the ASD effect = .2 cm). HC was approximately normally distributed in probands and unaffected relatives, with only a few outliers. Genetic deviation of HC was also normally distributed, consistent with a random sampling of parental genes. Whereas larger HC than expected was associated with ASD symptom severity and regression, IQ decreased with the absolute value of the genetic deviation of HC. CONCLUSIONS: Measured against expected values derived from covariates of ASD subjects, statistical outliers for HC were uncommon. HC is a strongly heritable trait, and population norms for HC would be far more accurate if covariates including genetic ancestry, height, and age were taken into account. The association of diminishing IQ with absolute deviation from predicted HC values suggests HC could reflect subtle underlying brain development and warrants further investigation.

Purpose: Impairments in the social use of language are universal in autism spectrum disorder (ASD), but few standardized measures evaluate communication skills above the level of individual words or sentences. This study evaluated the Expression, Reception, and Recall of Narrative Instrument (ERRNI; Bishop, 2004) to determine its contribution to assessing language and communicative impairment beyond the sentence level in children with ASD. Method: A battery of assessments, including measures of cognition, language, pragmatics, severity of autism symptoms, and adaptive functioning, was administered to 74 8- to 9-year-old intellectually able children with ASD. Results: Average performance on the ERRNI was significantly poorer than on the Clinical Evaluation of Language Fundamentals-Fourth Edition (CELF-4). In addition, ERRNI scores reflecting the number and quality of relevant story components included in the participants' narratives were significantly positively related to scores on measures of nonverbal cognitive skill, language, and everyday adaptive communication, and significantly negatively correlated with the severity of affective autism symptoms. Conclusion: Results suggest that the ERRNI reveals discourse impairments that may not be identified by measures that focus on individual words and sentences. Overall, the ERRNI provides a useful measure of communicative skill beyond the sentence level in school-aged children with ASD. [The Pathways in AST study team assisted in the writing of this article.]

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

BACKGROUND: Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. METHODS: By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. RESULTS: By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. CONCLUSIONS: Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability.

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.