Marisela Huerta

Application of DSM-5 Criteria for Autism Spectrum Disorder to Three Samples of Children With DSM-IV Diagnoses of Pervasive Developmental Disorders

OBJECTIVE Substantial revisions to the DSM-IV criteria for autism spectrum disorders (ASDs) have been proposed in efforts to increase diagnostic sensitivity and specificity. This study evaluated the proposed DSM-5 criteria for the single diagnostic category of autism spectrum disorder in children with DSM-IV diagnoses of pervasive developmental disorders (PDDs) and non-PDD diagnoses. METHOD Three data sets included 4,453 children with DSM-IV clinical PDD diagnoses and 690 with non-PDD diagnoses (e.g., language disorder). Items from a parent report measure of ASD symptoms (Autism Diagnostic Interview-Revised) and clinical observation instrument (Autism Diagnostic Observation Schedule) were matched to DSM-5 criteria and used to evaluate the sensitivity and specificity of the proposed DSM-5 criteria and current DSM-IV criteria when compared with clinical diagnoses. RESULTS Based on just parent data, the proposed DSM-5 criteria identified 91% of children with clinical DSM-IV PDD diagnoses. Sensitivity remained high in specific subgroups, including girls and children under 4. The specificity of DSM-5 ASD was 0.53 overall, while the specificity of DSM-IV ranged from 0.24, for clinically diagnosed PDD not otherwise specified (PDD-NOS), to 0.53, for autistic disorder. When data were required from both parent and clinical observation, the specificity of the DSM-5 criteria increased to 0.63. CONCLUSIONS These results suggest that most children with DSM-IV PDD diagnoses would remain eligible for an ASD diagnosis under the proposed DSM-5 criteria. Compared with the DSM-IV criteria for Aspergers disorder and PDD-NOS, the DSM-5 ASD criteria have greater specificity, particularly when abnormalities are evident from both parents and clinical observation.

DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes

The heterogeneous clinical presentations of individuals with autism spectrum disorders (ASDs) poses a significant challenge for sample characterization and limits the interpretability and replicability of research studies. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for ASD, with its dimensional approach, may be a useful framework to increase the homogeneity of research samples. In this review, we summarize the revisions to the diagnostic criteria for ASD, briefly highlight the literature supporting these changes, and illustrate how DSM-5 can improve sample characterization and provide opportunities for researchers to identify possible subtypes within ASD.

Exploring the relationship between anxiety and insistence on sameness in autism spectrum disorders.

Elevated anxiety symptoms are one of the most common forms of psychopathology to co‐occur with autism spectrum disorders (ASDs). The purpose of this study was to explore the association between anxiety and ASD symptoms, particularly the degree to which the relationship is explained by insistence on sameness (IS) behaviors and/or cognitive ability. The sample included 1429 individuals aged 5:8–18:0 years who participated in the Simons Simplex Collection, a genetic consortium study of ASD. Child Behavior Checklist Anxiety Problems T‐scores and Autism Diagnostic Interview‐Revised “IS“ item raw totals were treated as both categorical and continuous measures of anxiety and IS, respectively. Chronological age, verbal intelligence quotient (IQ), and a variety of ASD phenotype‐related and other behavioral variables were assessed for potential association with anxiety and IS. Anxiety and IS continuous variables were minimally, although significantly, associated with each other and with chronological age and verbal IQ. Neither anxiety nor IS was associated with other core autism diagnostic scores. Anxiety was associated with a variety of other psychiatric and behavioral symptoms in ASD, including irritability, attention problems, and aggression, while IS was not. Anxiety and IS appear to function as distinct constructs, each with a wide range of expression in children with ASD across age and IQ levels. Thus, both variables could be of use in ASD behavioral research or in dimensional approaches to genetic exploration. Unlike IS, however, anxiety is related to non‐ASD‐specific behavioral symptoms. Autism Res 2012, ●●: ●●–●●.

Diagnostic Evaluation of Autism Spectrum Disorders

Research on the identification and evaluation of autism spectrum disorders is reviewed, and best practices for clinical work are discussed. The latest research on diagnostic tools, and their recommended use, is also reviewed. Recommendations include the use of instruments designed to assess multiple domains of functioning and behavior, the inclusion of parents and caregivers as active partners, and the consideration of developmental factors throughout the diagnostic process.

Measuring social communication behaviors as a treatment endpoint in individuals with autism spectrum disorder

Social communication impairments are a core deficit in autism spectrum disorder. Social communication deficit is also an early indicator of autism spectrum disorder and a factor in long-term outcomes. Thus, this symptom domain represents a critical treatment target. Identifying reliable and valid outcome measures for social communication across a range of treatment approaches is essential. Autism Speaks engaged a panel of experts to evaluate the readiness of available measures of social communication for use as outcome measures in clinical trials. The panel held monthly conference calls and two face-to-face meetings over 14 months. Key criteria used to evaluate measures included the relevance to the clinical target, coverage of the symptom domain, and psychometric properties (validity and reliability, as well as evidence of sensitivity to change). In all, 38 measures were evaluated and 6 measures were considered appropriate for use, with some limitations. This report discusses the relative strengths and weaknesses of existing social communication measures for use in clinical trials and identifies specific areas in need of further development.

Utility of the Child Behavior Checklist as a Screener for Autism Spectrum Disorder

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. Autism Res 2015.

Multidimensional Influences on Autism Symptom Measures: Implications for Use in Etiological Research

OBJECTIVE Growing awareness that symptoms of autism spectrum disorder (ASD) transcend multiple diagnostic categories, and major advances in the identification of genetic syndromes associated with ASD, have led to widespread use of ASD symptom measures in etiologic studies of neurodevelopmental disorders. Insufficient consideration of potentially confounding factors such as cognitive ability or behavior problems can have important negative consequences in interpretation of findings, including erroneous estimation of associations between ASD and etiologic factors. METHOD Participants were 388 children 2 to 13 years old with diagnoses of ASD or another neurodevelopmental disorder without ASD. Receiver operating characteristics methods were used to assess the influence of IQ and emotional and behavioral problems on the discriminative ability of 3 widely used ASD symptom measures: the Social Responsiveness Scale (SRS), the Autism Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic Observation Schedule (ADOS). RESULTS IQ influenced the discriminative thresholds of the SRS and ADI-R, and emotional and behavioral problems affected the discriminative thresholds of the SRS, ADI-R, and ADOS. This resulted in low specificity of ASD cutoffs on the SRS and ADI-R for children with intellectual disability without ASD (27-42%) and low specificity across all 3 instruments for children without ASD with increased emotional and behavioral problems (36-59%). Adjustment for these characteristics resulted in improved discriminative ability for all of the ASD measures. CONCLUSION The findings indicate that scores on ASD symptom measures reflect far more than ASD symptoms. Valid interpretation of scores on these measures requires steps to account for the influences of IQ and emotional and behavioral problems.

The autism symptom interview, school‐age: A brief telephone interview to identify autism spectrum disorders in 5‐to‐12‐year‐old children

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.

The clinician perspective on sex differences in autism spectrum disorders

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.

Commentary: Advancing Measurement of ASD Severity and Social Competence: A Reply to Constantino and Frazier (2013).

The Social Responsiveness Scale (SRS) is currently being used in clinical and genetic studies of autism as both a screener and as a quantitative measure of autistic traits. Our article (Hus, Bishop, Gotham, Huerta & Lord, 2013) assessed the influence of nonspecific factors on SRS scores to aid researchers in their interpretations of these scores. In their commentary, Constantino and Frazier (2013) argue that the strong influence of behavior problems on the SRS represents the overlap between neuropsychiatric syndromes, and that behavioral symptoms reflected in SRS scores ‘might actually be caused by the autistic syndrome’ (p. 1). They cite evidence for substantial overlap in genetic associations between ASD, ADHD, and other child psychiatric disorders. Our concern, however, is that if scores on a measure do not distinguish between general behavior problems and autism symptoms, questions about overlap cannot even begin to be answered. Moreover, what was not noted in the commentary was the fact that we found equally large effects of behavior problems and smaller effects of social competence on SRS scores in typical siblings, who did not have ASD. It is widely recognized that children with ASD have varying levels of general behavior problems, and that many have comorbid conditions, such as ADHD, language delay and intellectual disability (Lundstr€ om et al., 2011; Simonoff et al., 2008). However, for researchers seeking to identify causal or riskrelated genetic influences, behavioral measures not confounded by these other behaviors are needed to draw conclusions that a particular finding is contributing to specific risk for ASD. Similarly, for researchers who want to evaluate associations between particular regions of the brain and core autism symptoms or social competence, evidence that measures such as the SRS are strongly influenced by general behavior problems would seem to present a problem in identifying the specificity of that region. Thus, our goal in Hus et al. (2013) was to determine the influences of non-specific factors known to affect scores on other ASD measures (Charman et al., 2007) to provide more informed interpretations of SRS scores. Given the SRS’s widespread use in genetic and neurobiological research, we hoped that we could increase the degree to which the SRS measured social competence and ASD symptoms, and thereby extend its utility in drawing associations between behavioral phenotypes and underlying biology. In a previous study, we found this approach was useful in improving the validity of scores on the autism diagnostic observation scale (ADOS). After the introduction of the ADOS, we learned that expressive language level and age (e.g., de Bildt et al., 2004) strongly influenced raw ADOS totals. Through expressive language and age-based algorithms (Gotham, Risi, Pickles & Lord, 2007) and the introduction of severity scores calibrated by the same dimensions, we were able to improve the degree to which the ADOS domain scores represent autism severity within the context of a clinical observation. The calibrated severity scores in the ADOS (Gotham, Pickles & Lord, 2009; Hus, Gotham & Lord, 2012) allow researchers to expand the boundaries of constructs of social-communication deficits and repetitive behaviors and quantify difficulties across an interval scale, rather than simply providing categorical cut-offs – contributing to the need for dimensional measures highlighted by Constantino and Frazier (2013). We approached the current analysis of the SRS from the same point of view. The SRS is particularly valuable because it provides a range of scores even within a typical population. We wondered if we could better understand what child factors could be controlled to make the SRS a more specific measure of social competence. Recently, Duku et al. (2012) took on a similar task with the SRS, resulting in selection of a subset of 30 items intended to measure social impairments in preschool children, but which still correlated with the CBCL internalizing and externalizing scales, r = 0.65–0.68. We started by looking for how the SRS related to the social domain of the Vineland Adaptive Behavior Scales, a parent report measure widely used as a measure of social competence (Gillespie-Lynch et al., 2012; Klin et al., 2007). We chose social competence because the SRS is commonly referred to as a quantitative measure of social reciprocity that