An Opportunity to Fill a Gap for Newborn Screening of Neurodevelopmental Disorders.

Screening newborns using genome sequencing is being explored due to its potential to expand the list of conditions that can be screened. Previously, we proposed the need for large-scale pilot studies to assess the feasibility of screening highly penetrant genetic neurodevelopmental disorders. Here, we discuss the initial experience from the GUARDIAN study and the systemic gaps in clinical services that were identified in the early stages of the pilot study.

Associations Between Parenting Stress and Quality Time in Families of Youth with Autism Spectrum Disorder.

Increased stress among parents of youth with ASD has been well-documented. However, research on aspects of the parent-child relationship and subsequent links to parenting stress is limited. We assessed parents (N = 511) of youth with ASD to examine relations between parenting stress and parent-child quality time (amount of quality time, shared enjoyment, synchronicity). Elevated parenting stress was associated with less time spent engaging with youth in shared activities and decreased parent and child enjoyment during shared interactions. Parents with elevated stress reported engaging in shared activities and experiencing synchronicity with their child less often than parents below the clinical threshold. Future research should emphasize longitudinal efforts examining the directionality of this relationship to better inform family-focused intervention.

Predictors of Aggression, Disruptive Behavior, and Anger Dysregulation in Youths with Autism Spectrum Disorder.

Youth with autism spectrum disorder (ASD) often experience difficulties related to aggression, disruptive behavior, and regulation of emotions that precipitate these behaviors (i.e., anger). The extent to which aggression, disruptive behaviors, and anger dysregulation are correlated with distinct or overlapping factors has not yet been explored. The present study examined whether aspects of participant demographics, individual youth functioning, caregiver stress, and family warmth contributed to youth aggression, disruptive behavior, and anger dysregulation. Participants were caregivers of 511 youths with ASD. Analyses revealed that significant proportions of variance in aggression, disruptive behaviors, and anger dysregulation were accounted for by shared variables pertaining to demographics, the individual youth, and caregiver stress. Implications of treatment and future research are discussed.

The network structure of the Special Interests Survey.

Despite the prevalence of special interests (SIs) in autistic youth, research on SIs and how they are characterized is limited. Indeed, a significant challenge in identifying and classifying SIs lies in capturing the vast and diverse scope of potential interests in this population. The recently developed Special Interest Survey (SIS) is a caregiver-report measure to improve SI characterization by capturing a broad range of past and current SIs. In the present study, we performed a network analysis of the SIS to examine relations between SIs and identify distinct interest clusters. We analyzed data from 1992 caregivers of autistic youths who completed the SIS. The network of SIs was densely interconnected, characterized by six communities of interests: Fact-seeking, Engineering, Order-seeking, Object Attachment, Entertainment, and Scholarly Pursuits. Findings suggest that the structure of the observed network is likely to generalize to similar samples. Of all the SIs and their respective communities, behaviors related to Fact-seeking were identified as the most central, meaning that endorsement of these interests was most strongly related to co-endorsement of other SIs. These findings lay the groundwork for future work on SIs, such as improved assessment techniques and linkage of SIs to a broad range of demographic variables, youth characteristics, and autism symptoms.

Measurement invariance of the Autism Impact Measure (AIM) across sex in children with autism spectrum disorder.

Measurement invariance, or the degree to which an instrument measures constructs consistently across subgroups, is critical for appropriate interpretations of measures. Given sex differences in the phenotypic and clinical presentation of autism spectrum disorder (ASD), it is particularly important to examine measurement invariance in autism instruments to ensure that ASD measures are not biased toward the more common male ASD phenotype. This study represents an important preliminary investigation evaluating the measurement equivalence of the Autism Impact Measure (AIM) across children and adolescents with ASD. The results indicated that the AIM demonstrated measurement invariance at the configural, metric, and scalar levels across sex in all five domains, including Repetitive Behavior, Communication, Atypical Behavior, Social Reciprocity, and Peer Interaction. These results suggest that ASD core symptoms assessed by the AIM were similar among male and female groups. In addition, the latent means for all five factors were not statistically significantly different across sex groups, revealing no systematic differences on any of the AIM subscales for males and females. Overall, this study showed that the AIM detects core ASD symptoms across all five areas equivalently in males and females and is not biased toward males with ASD.

Diagnostic Evaluations of Autism Spectrum Disorder during the COVID-19 Pandemic.

A global pandemic has significantly impacted the ability to conduct diagnostic evaluations for autism spectrum disorder (ASD). In the wake of the coronavirus, autism centers and providers quickly needed to implement innovative diagnostic processes to adapt in order to continue serve patient needs while minimizing the spread of the virus. The International Collaborative for Diagnostic Evaluation of Autism (IDEA) is a grassroots organization that came together to discuss standards of care during the pandemic and to provide a forum wherein providers communicated decisions. This white paper is intended to provide examples of how different centers adjusted their standard approaches to conduct diagnostic evaluations for ASD during the pandemic and to provide insight to other centers as they go through similar challenges.

Editorial Perspective: The autism waitlist crisis and remembering what families need.

Differential diagnosis of autism is very complex. Best practice guidelines in the US encourage the use of specialized tools by a highly trained provider. The need for this comprehensive evaluation, coupled with the increase in autism prevalence and awareness, has led to alarmingly long wait times for diagnostic evaluations. Several solutions are currently being researched to remedy this problem and relieve the pressure, including testing new devices or procedures that can speed up the diagnostic process. Creative solutions are welcomed; however, we urge caution in the use of new devices and methods without being fully vetted. Moreover, a quality assessment provides much more than just a designation of whether or not autism is present. Thus, even in cases when alternative means could be used to more quickly arrive at a diagnosis, a comprehensive assessment with a trained clinician is needed to guide recommendations and ongoing care.

Sex differences in scores on standardized measures of autism symptoms: a multisite integrative data analysis.

BACKGROUND: Concerns 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. METHODS: Data 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. RESULTS: Sex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES] < 0.20), increasing to small to moderate in adolescence (ES < 0.40). Boys received more severe RRB scores than girls on both the ADOS and ADI-R (age 4 + algorithm), and girls received more severe scores than boys on both SRS indices, which emerged in adolescence. CONCLUSIONS: This study combined several available databases to create the largest sample of girls with ASD diagnoses. We found minimal differences due to sex beyond other known influences on ASD severity indicators. This may suggest that, among children who ultimately receive a clinical ASD diagnosis, severity estimates do not systematically differ to such an extent that sex-specific scoring procedures would be necessary. However, given the limitations inherent in clinically ascertained samples, future research must address questions about systematic sex differences among children or adults who do not receive clinical diagnoses of ASD. Moreover, while the current study helps resolve questions about widely used diagnostic instruments, we could not address sex differences in phenotypic aspects outside of these scores.

ASD symptoms in toddlers and preschoolers: An examination of sex differences.

Although considerable work has documented higher prevalence rates of autism spectrum disorder (ASD) in boys, fewer studies have focused on sex differences within samples of young children at-risk for ASD. This study examined sex differences in ASD symptom domains and ASD screening outcomes among toddlers (18-35 months) and preschoolers (36-72 months) with ASD-related concerns. Participants included 480 children between 18 and 72 months evaluated by university-based ASD specialty clinics. Results revealed significant sex differences in severity of social communication (SC) deficits across age groups. Within the toddler group, girls diagnosed with ASD displayed greater SC deficits according to standardized observation and clinician severity ratings. Within the preschool group, girls diagnosed with ASD were rated by parents as having more severe SC deficits, but these differences were not corroborated by standardized observations or clinician ratings. No sex differences emerged for severity of restricted repetitive behaviors (RRBs) for either age group. Across the entire referred sample, boys and girls did not differ in terms of scores on commonly used screening instruments. Importantly, results suggest that two of the most commonly used ASD screeners (i.e., Modified-Checklist for Autism in Toddlers-Revised with Follow-up and Social Communication Questionnaire ) may underidentify RRBs in toddler and preschool-aged girls as screening scores were only influenced by severity of SC deficits. Greater SC deficits in young girls with ASD along with its impact on screening status suggests greater attention be placed on the under-identification of ASD in girls as well as current screening measures' ability to tap into the topography of ASD symptoms across genders. Autism Res 2020, 13: 157-166. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, we found that young girls diagnosed with autism spectrum disorder tend to have greater social communication deficits than young boys and that these differences vary by age. Specifically, toddler-aged girls receive higher clinician ratings of social communication deficits when compared to boys, while preschool-aged girls receive higher parent ratings of social communication deficits. For girls, current screening tools seem to be more highly influenced by severity of social communication deficits than by restricted repetitive behaviors.

Brief Report: Calculation and Convergent and Divergent Validity of a New ADOS-2 Expressive Language Score.

Despite the importance of expressive language for individuals with autism spectrum disorder (ASD), expressive language assessments are not consistently included in ASD research and many studies do not adequately describe participants' verbal abilities. A valid and efficient measure of expressive language would facilitate consistent reporting across ASD research studies and provide data for additional analyses. The current study developed a new Autism Diagnostic Observation Schedule (ADOS-2) expressive language score and examined convergent and divergent validity in a large, well-defined sample of children with ASD. This score was highly correlated with other measures of expressive language (including parent-report, direct assessment, and clinician ratings) and less strongly correlated with measures of receptive language and nonverbal cognitive ability, providing good evidence of convergent and divergent validity.

When Are We Sure? Predictors of Clinician Certainty in the Diagnosis of Autism Spectrum Disorder.

Differential diagnosis of autism spectrum disorder (ASD) is challenging, and uncertainty regarding a child's diagnosis may result in under-identification or prolonged diagnostic pathways. The current study examined diagnostic certainty, or how sure clinicians were that their diagnosis was accurate, among 478 toddler and preschool-aged children referred for possible ASD to academic medical specialty clinics. Overall, 60 percent of diagnoses were made with complete certainty. Clinicians were more certain when positively identifying ASD than ruling it out. Children presenting with a moderate (vs high or low) level of observable ASD symptoms were less likely to have a certain diagnosis. Further, clinicians rated less diagnostic certainty for older children, those with public insurance, and those with higher IQ and adaptive behavior abilities.

Screening in toddlers and preschoolers at risk for autism spectrum disorder: Evaluating a novel mobile-health screening tool.

There are many available tools with varying levels of accuracy designed to screen for Autism Spectrum Disorder (ASD) in young children, both in the general population and specifically among those referred for developmental concerns. With burgeoning waitlists for comprehensive diagnostic ASD assessments, finding accurate methods and tools for advancing diagnostic triage becomes increasingly important. The current study compares the efficacy of four oft used paper and pencil measures, the Modified Checklist for Autism in Toddlers Revised with Follow-up, the Social Responsiveness Scale, Second Edition, and the Social Communication Questionnaire, and the Child Behavior Checklist to a novel mobile-health screening tool developed by Cognoa, Inc. (Cognoa) in a group of children 18-72 months of age. The Cognoa tool may have potential benefits as it integrates a series of parent-report questions with remote clinical ratings of brief video segments uploaded via parent's smartphones to calculate level of ASD risk. Participants were referred to one of three tertiary care diagnostic centers for ASD-related concerns (n = 230) and received a best estimate ASD diagnosis. Analysis and comparison of psychometric properties indicated potential advantages for Cognoa within this clinical sample across age ranges not often covered by another single measure/tool. Autism Res 2018, 11: 1038-1049. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: With the wait times getting longer for comprehensive Autism Spectrum Disorder (ASD) diagnostic assessments, it is becoming increasingly important to find accurate tools to screen for ASD. The current study compares four screening measures that have been in use for some time to a novel mobile-health screening tool, called Cognoa. The Cognoa tool is novel because it integrates parent-report questions with clinical ratings of brief video segments uploaded via parent's smartphones to calculate ASD risk. Two hundred thirty children who were referred to one of three ASD specialty diagnostic centers to see if they had ASD participated in the study. A direct comparison indicated potential advantages for Cognoa not often covered by another single measure/tool.

A Prospective Study of the Concordance of DSM-IV and DSM-5 Diagnostic Criteria for Autism Spectrum Disorder.

The transition from DSM-IV to DSM-5 criteria for autism spectrum disorder (ASD) sparked considerable concern about the potential implications of these changes. This study was designed to address limitations of prior studies by prospectively examining the concordance of DSM-IV and final DSM-5 criteria on a consecutive sample of 439 children referred for autism diagnostic evaluations. Concordance and discordance were assessed using a consistent diagnostic battery. DSM-5 criteria demonstrated excellent overall specificity and good sensitivity relative to DSM-IV criteria. Sensitivity and specificity were strongest for children meeting DSM-IV criteria for autistic disorder, but poor for those meeting criteria for Asperger's disorder and pervasive developmental disorder. Higher IQ, older age, female sex, and less pronounced ASD symptoms were associated with greater discordance.

Cognitive Profiles in Youth with Autism Spectrum Disorder: An Investigation of Base Rate Discrepancies using the Differential Ability Scales--Second Edition.

Extant data suggest that the cognitive profiles of individuals with ASD may be characterized by variability, particularly in terms of verbal intellectual functioning (VIQ) and non-verbal intellectual functioning (NVIQ) discrepancies. The Differential Ability Scales, Second Edition (DAS-II) has limited data available on its use with youth with ASD. The current study examined data from 2,110 youth with ASD in order to characterize performance on the DAS-II and to investigate potential discrepancies between VIQ and NVIQ. A larger proportion of individuals in the ASD sample had significant discrepancies between VIQ and NVIQ when compared to the normative sample [early years sample χ2 (2) = 38.36; p < .001; school age sample χ2 (2) = 13.48; p < .01]. Clinical and research implications are discussed.

Multisystemic therapy for disruptive behavior problems in youths with autism spectrum disorders: a progress report.

Youths with autism spectrum disorders (ASD) often engage in serious disruptive behaviors that interfere with their ability to successfully manage day-to-day responsibilities and contribute to relationship problems with caregivers, peers, and teachers. Effective treatments are needed to address the factors linked with disruptive behavior problems in this population of youths. Multisystemic therapy (MST) is a comprehensive family- and community-based treatment approach that has been effective with other difficult-to-treat populations of youths and holds promise for youths with ASD. In this article, we review the broad range of factors associated with disruptive behaviors among youths with ASD and discuss how MST interventions can be adapted to address those factors. We also present a framework for our adaptation of the MST model for youths with ASD. This framework includes a recently completed pilot study as well as an ongoing efficacy trial that together have served to identify key interventions for our adaptation of the MST model.

Comprehensive comparison of self-administered questionnaires for measuring quantitative autistic traits in adults.

We comprehensively compared all available questionnaires for measuring quantitative autistic traits (QATs) in terms of reliability and construct validity in 3,147 non-clinical and 60 clinical subjects with normal intelligence. We examined four full-length forms, the Subthreshold Autism Trait Questionnaire (SATQ), the Broader Autism Phenotype Questionnaire, the Social Responsiveness Scale2-Adult Self report (SRS2-AS), and the Autism-Spectrum Quotient (AQ). The SRS2-AS and the AQ each had several short forms that we also examined, bringing the total to 11 forms. Though all QAT questionnaires showed acceptable levels of test-retest reliability, the AQ and SRS2-AS, including their short forms, exhibited poor internal consistency and discriminant validity, respectively. The SATQ excelled in terms of classical test theory and due to its short length.

The Autism Impact Measure (AIM): initial development of a new tool for treatment outcome measurement.

The current study describes the development and psychometric properties of a new measure targeting sensitivity to change of core autism spectrum disorder (ASD) symptoms, the Autism Impact Measure (AIM). The AIM uses a 2-week recall period with items rated on two corresponding 5-point scales (frequency and impact). Psychometric properties were examined using a large sample (n = 440) of children with ASD enrolled in the Autism Treatment Network. The exploratory factor analysis indicated four factors and resulted in a 25-item questionnaire with excellent overall model fit. Test-retest reliability, cross-informant reliability, and convergent validity with other measures of ASD symptoms and overall functioning were strong. The AIM is a reliable and valid measure of frequency and impact of core ASD symptoms.

Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders.

Children with autism spectrum disorders (ASD) experience high rates of anxiety, sensory processing problems, and gastrointestinal (GI) problems; however, the associations among these symptoms in children with ASD have not been previously examined. The current study examined bivariate and multivariate relations among anxiety, sensory over-responsivity, and chronic GI problems in a sample of 2,973 children with ASD enrolled in the Autism Treatment Network (ages 2-17 years, 81.6 % male). Twenty-four percent of the sample experienced at least one type of chronic GI problem (constipation, abdominal pain, bloating, diarrhea, and/or nausea lasting three or more months). Children with each type of GI problem had significantly higher rates of both anxiety and sensory over-responsivity. Sensory over-responsivity and anxiety were highly associated, and each provided unique contributions to the prediction of chronic GI problems in logistic regression analyses. The results indicate that anxiety, sensory over-responsivity and GI problems are possibly interrelated phenomenon for children with ASD, and may have common underlying mechanisms.

A multisite study of the clinical diagnosis of different autism spectrum disorders.

CONTEXT: Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. OBJECTIVE: To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. DESIGN: Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. SETTING: Participants were recruited through 12 university-based autism service providers into a genetic study of autism. PARTICIPANTS: A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. MAIN OUTCOME MEASURE: Best-estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. RESULTS: Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. CONCLUSIONS: Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors, together with characteristics such as language level and cognitive function.