Improving autism identification and support for individuals assigned female at birth: clinical suggestions and research priorities.

Emerging evidence suggests that the higher prevalence of autism in individuals who are assigned male than assigned female at birth results from both biological factors and identification biases. Autistic individuals who are assigned female at birth (AFAB) and those who are gender diverse experience health disparities and clinical inequity, including late or missed diagnosis and inadequate support. In this Viewpoint, an international panel of clinicians, scientists, and community members with lived experiences of autism reviewed the challenges in identifying autism in individuals who are AFAB and proposed clinical and research directions to promote the health, development, and wellbeing of autistic AFAB individuals. The recognition challenges stem from the interplay between cognitive differences and nuanced or different presentations of autism in some AFAB individuals; expectancy, gender-related, and autism-related biases held by clinicians; and social determinants. We recommend that professional development for clinicians be supported by health-care systems, professional societies, and governing bodies to improve equitable access to assessment and earlier identification of autism in AFAB individuals. Autistic AFAB individuals should receive tailored support in education, identity development, health care, and social and professional sense of belonging.

Defining Positive Outcomes in More and Less Cognitively Able Autistic Adults.

Identifying positive outcomes for a wide range of intellectual abilities in autism spectrum disorder (ASD) remains a challenge. Several past studies of autistic adults have used outcome definitions that do not reflect the experiences of less cognitively able adults. The aim of the current study was to (1) define three domains of outcomes: autonomy, social relationships, and purpose, and (2) examine how these outcomes relate to concurrent aspects of adult functioning. Using data from a longitudinal sample of 126 adults (85% diagnosed with ASD at some point), mean age 26, who first entered the study in early childhood, we generated distinct outcomes for less (daily living skills above an 8-year-old level, having regular activities outside the home, and social contacts outside the family) and more cognitively able adults (living independently, having paid employment, and at least one true friend). Verbal IQ, assessed in adulthood, was a significant predictor of more outcomes achieved for individuals within more and less cognitively able groups. For less cognitively able adults, having ever received a formal ASD diagnosis (in contrast to current Autism Diagnostic Observation Schedule [ADOS] CSS scores) was associated with lower odds of positive outcomes. For more cognitively able adults, living skills and happiness measures were positively associated with number of outcomes met; higher ADOS CSS, internalizing and externalizing symptoms, being racially diverse, and having caregiver education below college graduation were all negatively associated with the number of positive outcomes. Tailoring outcomes to ability levels may lead to better identification of goals and service needs. LAY SUMMARY: This article describes the outcomes of autistic adults who are more and less cognitively able. For less cognitively able individuals, an earlier autism diagnosis was negatively related to outcomes. Several factors that were associated with positive outcomes for more cognitively able individuals, including daily living skills, fewer mental health problems, family demographics, and subjective measures of happiness. Our study identifies several important factors for families, individuals, and service providers to consider and discuss when planning the transition to adulthood. Autism Res 2020, 13: 1548-1560. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Work, living, and the pursuit of happiness: Vocational and psychosocial outcomes for young adults with autism.

LAY ABSTRACT: It is important to better understand how adults with autism are functioning in adulthood. Studies that have tracked individuals across the lifespan can help identify developmental factors influence differences in adult outcomes. The present study examines the independence, well-being, and functioning of 123 adults that have been closely followed since early childhood. Autism diagnosis and cognitive assessments were given frequently throughout childhood and during adulthood. We examined differences between adults who had received an autism diagnosis at some point with higher cognitive abilities (Ever ASD-High IQ) and lower cognitive abilities (Ever ASD-Low IQ), as well as adults who never received a diagnosis of autism in the course of the study (Never ASD). We found that autistic features specifically related to adaptive skills and friendships, and verbal intelligence related to work outcomes. In many ways, the Never ASD group had similar outcomes compared to the ASD groups. However, adults with ASD tended to have lower well-being and fewer positive emotions. Families played a major role in supporting adults with and without ASD at all intellectual levels. The findings suggest that realistic ways of increasing independence need to be developed by working with adults and their families, while acknowledging the contribution of individual differences in mental health, intelligence and autism symptoms across neurodevelopmental disorders.

The adult outcome of children referred for autism: typology and prediction from childhood.

BACKGROUND: Autism Spectrum Disorder is highly heterogeneous, no more so than in the complex world of adult life. Being able to summarize that complexity and have some notion of the confidence with which we could predict outcome from childhood would be helpful for clinical practice and planning. METHODS: Latent class profile analysis is applied to data from 123 participants from the Early Diagnosis Study (Lord et al., Archives of General Psychiatry, 2006, 63, 694) to summarize in a typology the multifacetted early adult outcome of children referred for autism around age 2. The form of the classes and their predictability from childhood is described. RESULTS: Defined over 15 measures, the adult outcomes were reduced to four latent classes, accounting for much of the variation in cognitive and functional measures but little in the affective measures. The classes could be well and progressively more accurately predicted from childhood IQ and symptom severity measurement taken at age 2 years to age 9 years. Removing verbal and nonverbal IQ and autism symptom severity measurement from the profile of adult measures did not change the number of the latent classes; however, there was some change in the class composition and they were more difficult to predict. CONCLUSIONS: While an empirical summary of adult outcome is possible, careful consideration needs to be given to the aspects that should be given priority. An outcome typology that gives weight to cognitive outcomes is well predicted from corresponding measures taken in childhood, even after account for prediction bias from fitting a complex model to a small sample. However, subjective well-being and affective aspects of adult outcome were weakly related to functional outcomes and poorly predicted from childhood.

The Adapted ADOS: A New Module Set for the Assessment of Minimally Verbal Adolescents and Adults.

Few measures are appropriate to assess autism symptoms in minimally verbal adolescents and adults. The Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2, Lord et al., in Autism diagnostic observation schedule-2nd edition (ADOS-2). Western Psychological Services, Los Angeles, 2012) Modules 1 and 2 were designed and validated with children whose spoken language ranges from few- to- no words to phrase speech. This study describes the development and initial validation of the Adapted-ADOS (A-ADOS), which includes tasks, materials and behavioral codes modified to be suitable for assessing older minimally verbal individuals. A-ADOS algorithms exhibit comparable sensitivity and improved specificity relative to ADOS-2 Modules 1 and 2. Although further validation is needed, the A-ADOS will facilitate research to further understanding of minimally verbal adults and symptom trajectories across the lifespan.

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.

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. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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.

Subdimensions of social-communication impairment in autism spectrum disorder.

BACKGROUND: More refined dimensions of social-communication impairment are needed to elucidate the clinical and biological boundaries of autism spectrum disorders (ASD) and other childhood onset psychiatric disorders associated with social difficulties, as well as to facilitate investigations in treatment and long-term outcomes of these disorders. METHODS: This study was intended to identify separable dimensions of clinician-observed social-communication impairments by examining scores on a widely used autism diagnostic instrument. Participants included verbally fluent children ages 3-13 years, who were given a clinical diagnosis of ASD (n = 120) or non-ASD (i.e. ADHD, language disorder, intellectual disability, mood or anxiety disorder; n = 118) following a comprehensive diagnostic assessment. Exploratory and confirmatory factor analysis examined the factor structure of algorithm items from the Autism Diagnostic Observation Schedule (ADOS), Module 3. RESULTS: Results indicated that a three-factor model consisting of repetitive behaviors and two separate social-communication behavior factors had superior fit compared to a two-factor model that included repetitive behaviors and one social-communication behavior factor. In the three-factor model, impairments in 'Basic Social-Communication' behaviors (e.g. eye contact, facial expressions, gestures) were separated from impairments in 'Interaction quality.' Confirmatory factor analysis in an independent sample of children in the Simons Simplex Collection (SSC) further supported the division of social-communication impairments into these two factors. Scores in Interaction Quality were significantly associated with nonverbal IQ and male sex in the ASD group, and with age in the non-ASD group, while scores in basic social communication were not significantly associated with any of these child characteristics in either diagnostic group. CONCLUSIONS: Efforts to conceptualize level, or severity, of social-communication impairment in children with neurodevelopmental disorders might be facilitated by separating the most basic (or proximal) social-communication impairments from those that could arise from a range of other phenotypic variables. Identification of social-communication subdimensions also highlights potential avenues for measuring different types of social-communication impairments for different purposes (e.g. for differential diagnosis vs. response to treatment).

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.

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.

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.

Subcategories of restricted and repetitive behaviors in children with autism spectrum disorders.

Research suggests that restricted and repetitive behaviors (RRBs) can be subdivided into repetitive sensory motor (RSM) and insistence on sameness (IS) behaviors. However, because the majority of previous studies have used the autism diagnostic interview-revised (ADI-R), it is not clear whether these subcategories reflect the actual organization of RRBs in ASD. Using data from the Simons simplex collection (n = 1,825), we examined the association between scores on the ADI-R and the repetitive behavior scale-revised. Analyses supported the construct validity of RSM and IS subcategories. As in previous studies, IS behaviors showed no relationship with IQ. These findings support the continued use of RRB subcategories, particularly IS behaviors, as a means of creating more behaviorally homogeneous subgroups of children with ASD.

Factors influencing scores on the social responsiveness scale.

BACKGROUND: The Social Responsiveness Scale (SRS) is a parent-completed screening questionnaire often used to measure autism spectrum disorders (ASD) severity. Although child characteristics are known to influence scores from other ASD-symptom measures, as well as parent-questionnaires more broadly, there has been limited consideration of how non-ASD-specific factors may affect interpretation of SRS scores. Previous studies have explored effects of behavior problems on SRS specificity, but have not addressed influences on the use of the SRS as a quantitative measure of ASD-symptoms. METHOD: Raw scores (SRS-Raw) from parent-completed SRS were analyzed for 2,368 probands with ASD and 1,913 unaffected siblings. Regression analyses were used to assess associations between SRS scores and demographic, language, cognitive, and behavior measures. RESULTS: For probands, higher SRS-Raw were associated with greater non-ASD behavior problems, higher age, and more impaired language and cognitive skills, as well as scores from other parent report measures of social development and ASD-symptoms. For unaffected siblings, having more behavior problems predicted higher SRS-Raw; male gender, younger age, and poorer adaptive social and expressive communication skills also showed small, but significant effects. CONCLUSIONS: When using the SRS as a quantitative phenotype measure, the influence of behavior problems, age, and expressive language or cognitive level on scores must be considered. If effects of non-ASD-specific factors are not addressed, SRS scores are more appropriately interpreted as indicating general levels of impairment, than as severity of ASD-specific symptoms or social impairment. Additional research is needed to consider how these factors influence the SRS' sensitivity and specificity in large, clinical samples including individuals with disorders other than ASD.

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 Asperger's disorder and PDD-NOS, the DSM-5 ASD criteria have greater specificity, particularly when abnormalities are evident from both parents and clinical observation.