Commentary: Best practices and processes for assessment of autism spectrum disorder - the intended role of standardized diagnostic instruments.

Development of standardized diagnostic instruments has facilitated the systematic characterization of individuals with autism spectrum disorders (ASD) in clinical and research settings. However, overemphasis on scores from specific instruments has significantly detracted from the original purpose of these tools. Rather than provide a definitive "answer," or even a confirmation of diagnosis, standardized diagnostic instruments were designed to aid clinicians in the process of gathering information about social communication, play, and repetitive and sensory behaviors relevant to diagnosis and treatment planning. Importantly, many autism diagnostic instruments are not validated for certain patient populations, including those with severe vision, hearing, motor, and/or cognitive impairments, and they cannot be administered via a translator. In addition, certain circumstances, such as the need to wear personal protective equipment (PPE), or behavioral factors (e.g., selective mutism) may interfere with standardized administration or scoring procedures, rendering scores invalid. Thus, understanding the uses and limitations of specific tools within specific clinical or research populations, as well as similarities or differences between these populations and the instrument validation samples, is paramount. Accordingly, payers and other systems must not mandate the use of specific tools in cases when their use would be inappropriate. To ensure equitable access to appropriate assessment and treatment services, it is imperative that diagnosticians be trained in best practice methods for the assessment of autism, including if, how, and when to appropriately employ standardized diagnostic instruments.

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.

Editorial Perspective: Longitudinal research in autism - introducing the concept of 'chronogeneity'.

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

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).

Understanding definitions of minimally verbal across instruments: evidence for subgroups within minimally verbal children and adolescents with autism spectrum disorder.

BACKGROUND: Minimally verbal (MV) children with autism spectrum disorder (ASD) are often assumed to be profoundly cognitively impaired and excluded from analyses due to challenges completing standardized testing protocols. A literature aimed at increasing understanding of this subgroup is emerging; however, the many methods used to define MV status make it difficult to compare studies. Understanding how different instruments and definitions used to identify MV children affect sample composition is critical to advance research on this understudied clinical population. METHOD: The MV status of 1,470 school-aged children was defined using five instruments commonly used in ASD research. MV sample composition was compared across instruments. Analyses examined the proportion of overlap across MV subgroups and the extent to which child characteristics varied across MV subgroups defined using different definitions or combinations of measures. RESULTS: A total of 257 children were classified as MV on at least one instrument. Proportion of overlap between definitions ranged from 3% to 100%. The stringency of definition (i.e. few-to-no vs. some words) was associated with differences in cognitive and adaptive functioning; more stringent definitions yielded greater consistency of MV status across instruments. Cognitive abilities ranged from profoundly impaired to average intelligence; 16% had NVIQ ≥ 70. Approximately half exhibited verbal skills commensurate with nonverbal cognitive ability, whereas half had verbal abilities significantly lower than their estimated NVIQ. CONCLUSIONS: Future studies of MV children must carefully consider the methods used to identify their sample, acknowledging that definitions including children with 'some words' may yield larger samples with a wider range of language and cognitive abilities. Broadly defined MV samples may be particularly important to delineate factors interfering with language development in the subgroup of children whose expressive impairments are considerably below their estimated nonverbal cognitive abilities.

Use of machine learning to improve autism screening and diagnostic instruments: effectiveness, efficiency, and multi-instrument fusion.

BACKGROUND: Machine learning (ML) provides novel opportunities for human behavior research and clinical translation, yet its application can have noted pitfalls (Bone et al., 2015). In this work, we fastidiously utilize ML to derive autism spectrum disorder (ASD) instrument algorithms in an attempt to improve upon widely used ASD screening and diagnostic tools. METHODS: The data consisted of Autism Diagnostic Interview-Revised (ADI-R) and Social Responsiveness Scale (SRS) scores for 1,264 verbal individuals with ASD and 462 verbal individuals with non-ASD developmental or psychiatric disorders, split at age 10. Algorithms were created via a robust ML classifier, support vector machine, while targeting best-estimate clinical diagnosis of ASD versus non-ASD. Parameter settings were tuned in multiple levels of cross-validation. RESULTS: The created algorithms were more effective (higher performing) than the current algorithms, were tunable (sensitivity and specificity can be differentially weighted), and were more efficient (achieving near-peak performance with five or fewer codes). Results from ML-based fusion of ADI-R and SRS are reported. We present a screener algorithm for below (above) age 10 that reached 89.2% (86.7%) sensitivity and 59.0% (53.4%) specificity with only five behavioral codes. CONCLUSIONS: ML is useful for creating robust, customizable instrument algorithms. In a unique dataset comprised of controls with other difficulties, our findings highlight the limitations of current caregiver-report instruments and indicate possible avenues for improving ASD screening and diagnostic tools.

Recent advances in autism research as reflected in DSM-5 criteria for autism spectrum disorder.

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

Perspectives on Employer-Initiated Terminations Among Young Adults on the Autism Spectrum.

Job instability is high among autistic adults, with employer-initiated terminations a common reason for job loss. The current study used qualitative methods to code reasons that autistic adults identified for their employer-initiated termination. From 315 autistic individuals ages 18-35 who completed an online survey, 93 (29.5%) reported having been terminated from a job. These individuals were asked about the reasons for their termination and responses were coded into thematic categories. Common reasons included work performance, social difficulties, attendance, and mental health challenges. Adults were more likely to attribute terminations to internal causes (related to the individual) than to external causes (environment-related). A good fit between workplace, individual preferences, skills, and abilities is likely key to promoting job continuity for autistic adults.

Associations between social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder: Testing the indirect effects of loneliness.

LAY ABSTRACT: Previous studies have found that social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder are related. To better understand the relationship between these issues, this study examined the frequency of various types of social activities as well as if the participants felt that the frequency of time spent in the activity met their personal needs. In addition, the role of loneliness was tested as a possible way to understand the relationship between activities and depressive symptoms. To test these ideas, 321 participants who were recruited from the Simons Foundation Powering Autism Research for Knowledge (SPARK) research match registry and completed online measures of social activities, depressive symptoms, and loneliness. While the specific pattern was different for individual activities, it was found that those who felt that their current frequency of activities did not meet their needs had higher rates of depressive symptoms than those who felt they did meet their needs. Also, loneliness helps to understand relationship between social activities and depressive symptoms. The findings were discussed in light of previous study findings, interpersonal theories of depression, and clinical implications.

Associations between Social Experiences and Psychological Health for Autistic Youth with Low IQ.

PURPOSE: Social experiences are consistently associated with psychological health among autistic individuals. However, most extant studies on this topic exclude individuals with autism who have lower IQ or are otherwise unable to self-report. The current study addresses this gap by examining associations of negative peer experiences and social participation with psychological health among autistic youth with low IQ. METHODS: An online survey was collected from 268 parents of autistic adolescents and adults ages 15-25. Negative peer experiences included measures of peer victimization and being ignored. Social participation was assessed by the amount of participation and parents' perceptions of whether their youth felt the amount of participation was meeting their needs. Psychological health was assessed by parents' report of their youth's psychological quality of life, as well as whether they felt their son/daughter was currently depressed. RESULTS: Results suggested low rates of social participation in this sample, with relatively high rates of being ignored. Regression analysis found that lower rates of peer victimization and more activities in which parents perceived that the amount of time was meeting their youth's needs was associated with higher psychological quality of life and lower likelihood that parents felt their son/daughter was depressed. CONCLUSION: Though youth with autism and low IQ are often excluded from interventions aimed at improving social experiences, these findings suggest that promoting positive social experiences and ameliorating negative ones might be an avenue to improving psychological health in this group.

Self-reported Everyday Sources of Happiness and Unhappiness in Autistic Adults.

PURPOSE: Daily mood can be influenced by a range of experiences. Identifying everyday life experiences that make autistic adults happy and unhappy holds potential to foster positive mood and tackle mental health problems amongst this group. METHODS: A total of 293 autistic adults between the ages of 18 to 35 years old (mean age of 26.51 years old (SD = 4.62); 43.3% female gender, 4.8% nonbinary) provided open-text responses regarding everyday sources of happiness and unhappiness. Using an iterative process of inductive coding, 14 happy themes and 22 unhappy themes of mood-changing life experiences were identified based on self-report qualitative data. RESULTS: Common themes across the happy and unhappy domain involved social partners, social interactions, and engagement in recreational and employment activities, with additional distinct themes specific to happy or unhappy mood. Top themes identified in the happy domain emphasizes encouraging quality relationships and positive interactions with others and cultivating supportive work/societal environments to build a sense of achievement and value. Meanwhile, emotional tolls accompanied negative relationships and interactions, underscoring the necessity to provide autistic adults with conflict resolution and coping skills to increase feelings of happiness. CONCLUSION: Overall, the wide range of sources of happy and unhappy everyday experiences highlights the importance of considering personal preferences in engagement with others and activities in treatment.

In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months.

Importance: Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking. Objective: To determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age. Design, Setting, and Participants: This prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely. Exposure: In utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed. Main Outcomes and Measures: Neurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay. Results: A total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07). Conclusions and Relevance: Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.

Measuring autism-associated traits in the general population: Factor structure and measurement invariance across sex and diagnosis status of the Social Communication Questionnaire.

LAY ABSTRACT: Using questionnaires in research relies on the expectation that they measure the same things across different groups of individuals. If this is not true, then interpretations of results can be misleading when researchers compare responses across different groups of individuals or use in it a group that differs from that in which the questionnaire was developed. For the questionnaire we investigated, the Social Communication Questionnaire (SCQ), we found that parents of boys and girls responded to questionnaire items in largely the same way but that the SCQ measured traits and behaviors slightly differently depending on whether the children had autism. Based on these results, we concluded that researchers using this questionnaire should carefully consider these differences when deciding how to interpret findings. SCQ scores as a reflection of "autism-associated traits" in samples that are mostly or entirely made up of individuals without an autism diagnosis may be misleading and we encourage a more precise interpretation of scores as a broader indication of social-communicative and behavioral traits.

Neurodevelopmental profiles of 4-year-olds in the Navajo Birth Cohort Study.

Objective: Native American children disproportionally face many risk factors for poor developmental outcomes; these factors include poverty, environmental toxicant exposure, and limited medical, and intervention services. To understand these risks, comprehensive documentation of developmental and behavioral phenotypes are needed. In the current descriptive study, we assessed the neurodevelopment of young Diné (Navajo) children using standardized assessment instruments in combination with expert clinician judgment. Methods: As part of an ongoing, population-based, prospective birth cohort study, we conducted comprehensive neurodevelopmental assessments of 138, 3-5-year-old, Diné children residing on or near the Navajo Nation. We report results from standardized parent reports, psychiatric examinations, and direct assessments of children's language, cognitive, adaptive, and social-emotional development, as well as best estimate clinical diagnoses. Results: Forty-nine percent of our sample met DSM-5 criteria for a neurodevelopmental disorder (NDD) diagnosis. Language and speech sound disorders were most common, although autism spectrum disorder (ASD) was also elevated compared to the general population. Though language performance was depressed amongst all groups of children with, and without, NDDs, those meeting criteria for certain NDDs performed significantly lower on all language measures, when compared to those without. Social-emotional, behavioral, and nonverbal cognitive ability were in the average range overall. Conclusions: Diné children in our study were found to have a high percentage of clinically significant developmental delays. Overall, children presented with a pervasive pattern of depressed language performance across measures, irrespective of diagnosis (or no diagnosis), while other domains of functioning were similar to normative samples. Findings support the need to identify appropriate intervention and educational efforts for affected youth, while also exploring the causes of the specific developmental delays. However, longitudinal studies are necessary to establish best practices for identifying delays and delineating resilience factors to optimize development of Diné children.

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

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

Job loss predicts worsening depressive symptoms for young adults with autism: A COVID-19 natural experiment.

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

Developmental Variability in Autism Across 17 000 Autistic Individuals and 4000 Siblings Without an Autism Diagnosis: Comparisons by Cohort, Intellectual Disability, Genetic Etiology, and Age at Diagnosis.

Importance: Presence of developmental delays in autism is well established, yet few studies have characterized variability in developmental milestone attainment in this population. Objective: To characterize variability in the age at which autistic individuals attain key developmental milestones based on co-occurring intellectual disability (ID), presence of a rare disruptive genetic variant associated with neurodevelopmental disorders (NDD), age at autism diagnosis, and research cohort membership. Design: The study team harmonized data from 4 cross-sectional autism cohorts: the Autism Genetics Research Exchange (n = 3284; 1997-2015), The Autism Simplex Collection (n = 694; 2008-2011), the Simons Simplex Collection (n = 2753; 2008-2011), and the Simons Foundation Powering Autism Research for Knowledge (n = 10 367; 2016-present). The last sample further included 4145 siblings without an autism diagnosis or ID. Participants: Convenience sample of 21 243 autistic individuals or their siblings without an autism diagnosis aged 4 to 17 years. Main Outcomes and Measures: Parents reported ages at which participants attained key milestones including smiling, sitting upright, crawling, walking, spoon-feeding self, speaking words, speaking phrases, and acquiring bladder and bowel control. A total of 5295 autistic individuals, and their biological parents, were genetically characterized to identify de novo variants in NDD-associated genes. The study team conducted time-to-event analyses to estimate and compare percentiles in time with milestone attainment across autistic individuals, subgroups of autistic individuals, and the sibling sample. Results: Seventeen thousand ninety-eight autistic individuals (mean age, 9.15 years; 80.8% male) compared with 4145 siblings without autism or ID (mean age, 10.2 years; 50.2% female) showed delays in milestone attainment, with median (IQR) delays ranging from 0.7 (0.3-1.6) to 19.7 (11.4-32.2) months. More severe and more variable delays in autism were associated with the presence of co-occurring ID, carrying an NDD-associated rare genetic variant, and being diagnosed with autism by age 5 years. More severe and more variable delays were also associated with membership in earlier study cohorts, consistent with autism's diagnostic and ascertainment expansion over the last 30 years. Conclusions and Relevance: As the largest summary to date of developmental milestone attainment in autism, to our knowledge, this study demonstrates substantial developmental variability across different conditions and provides important context for understanding the phenotypic and etiological heterogeneity of autism.

Patterns of sleep disturbances and associations with depressive symptoms in autistic young adults.

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

Corrigendum: Bias in measurement of autism symptoms by spoken language level and non-verbal mental age in minimally verbal children with neurodevelopmental disorders.

[This corrects the article DOI: 10.3389/fpsyg.2022.927847.].