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Adult autism studies are increasingly comprised of later-diagnosed adults, yet little is known about how these adults compare to those diagnosed earlier in life. The present study examines medical and psychiatric conditions endorsed by autistic adults and documents differences between those diagnosed with ASD in childhood versus adulthood, as well as across age groups and sex at birth. 4657 legally independent adults (ages 18-85, M = 33.4 years) with professional ASD diagnoses who completed a medical questionnaire were drawn from the Simons Powering Autism Research Knowledge (SPARK) study. Chi square analyses, t-tests, and logistic regressions were used to compare medical and psychiatric conditions between age groups, sex at birth and adults diagnosed in childhood (before age 21) versus adulthood (at or after 21 years). Overall number of conditions endorsed as being diagnosed by a professional was high, with an average of 1.69 (SD = 2.01) medical or developmental and 2.98 (SD = 2.29) psychiatric conditions reported across the sample. Females were more likely to endorse psychiatric conditions (OR = 1.68). Adult-diagnosed adults were more likely to endorse psychiatric conditions (OR = 2.71) and reported more lifetime psychiatric diagnoses (M = 3.15, SD = 2.23) than their childhood-diagnosed counterparts (M = 2.81, SD = 2.33). These findings underscore the need for research to better understand and treat co-occurring psychiatric conditions in autistic adults and report and consider the age of diagnosis in adult autism samples. Moreover, results suggest it is imperative that mental health professionals receive autism training to promote accurate differential diagnosis and equitable access to mental health care for autistic adults with co-occurring psychiatric conditions.

It is essential to recognize the strengths and talents of autistic individuals. Previous studies of extraordinary talents (i.e. skills that stand out relative to the general population) have combined individuals with different skills (e.g. calendrical calculation, drawing) into one group. There has been limited investigation of talents in specific areas and even less consideration of personal strengths (i.e. skills that stand out relative to that person’s other abilities, but not the general population). We extend this literature by examining the relationship between parent-reported talents and strengths and performance on standardized cognitive tests in 1470 children (4–18 years) from the Simons Simplex Collection with autism and IQ above 70. Almost half (46%) had at least one parent-reported talent and an additional 23% without extraordinary talents had at least one personal strength. Children with parent-reported talents and strengths had different cognitive profiles than children with no reported skill in visuospatial, drawing, computation, or music. Those highlighted for their memory abilities had somewhat more even verbal and nonverbal abilities, relative to children whose memory was not emphasized as a special skill. These results emphasize the importance of exploring strengths separately by domain and a need for more research in this area. Lay abstract Previous research has suggested that focusing on impairments can be detrimental to the well-being of autistic individuals, yet little research has focused on strengths and positive qualities in autism. Some studies explored “savant skills” (herein referred to as “extraordinary talents”), that is, skills that stand out compared to the general population. These often group everyone who has a specific talent, rather than exploring subgroups with strengths in specific areas. There has been even less research focused on personal strengths (i.e. skills that stand out relative to the individual’s other abilities, but not the general population). To expand this research, we use a sample of 1470 children (ages 4–18 years) from the Simons Simplex Collection without cognitive impairment to examine the relationship between having a parent-reported skill in a specific area and performance on a standardized cognitive test. Almost half (46%) had at least one parent-reported talent and an additional 23% without extraordinary talents had at least one personal strength. Children with these parent-reported skills had different patterns of performance on these standardized tests than children without skills in that area (i.e. visuospatial, drawing, computation, reading, and memory). Specific skills in computation or reading were associated with higher overall performance on the standardized tests. These results emphasize the importance of considering strengths separately by area, rather than combining individuals with different types of strengths. The high number of children with skills in this study underscores the need for more research in this area, particularly using instruments focused on understanding the nuances of these strengths. It is important for future studies to consider these skills in children with cognitive impairment.

The COVID‐19 pandemic has disrupted autism research and services. Early career researchers (ECRs) are particularly vulnerable to the impact of the pandemic on job security and career development. The goal of this study was to capture the challenges ECRs are facing during the pandemic and the supports that are needed for career development and research. ECRs were invited to complete an online survey that focused on four major areas; the impact of COVID‐19 on their research; changes in productivity due to COVID‐19; changes to training due to COVID‐19; and current mental health. 150 ECRs were eligible and provided sufficient data for inclusion. All but one ECRs reported their research had been negatively impacted by the pandemic. Reductions in productivity were reported by 85% of ECRs. The biggest impacts included recruitment of participants, increased needs at home and personal mental health. ECRs reported a 3‐fold increase in burnout, as well as increased anxiety. ECR supports, such as funding, flexibility, and tenure extensions, are required to ensure ASD research does not suffer from a “lost generation” of researchers. Lay Summary The COVID‐19 pandemic has had negative impacts on research around the world. Loss of productivity impedes autism research discoveries. However, researchers in the earliest phases of their career, specifically postdoctoral fellows through individuals in assistant professor (or equivalent) positions, are particularly vulnerable to long‐lasting effects of pandemic‐related disruptions which may limit their ability to continue as autism researchers. This survey highlights the needs of this group and identifies mechanisms by which these early career researchers may be supported in this time. This is critical to ensure the next generation of ASD researchers and clinician scientists continue on the path to advancing understanding of autism in the decades to come.

Physical and psychiatric health conditions affect the lives of many autistic adults. However, relatively little is known about individual trajectories in autistic individuals' physical and mental health from adolescence to adulthood.This study uses a well-characterized longitudinal sample (Seizure onset continued well into adulthood, with two individuals experiencing their first seizure at the age of 25 years. Seizures and neuropsychiatric medication use were both higher for those with lower intelligence quotient (IQs). In addition, medication use increased over time for these individuals, whereas those with higher IQs saw a reduction in medication use with age. Between the ages of 15 to 30 years, the predicted probability of medication use increased from 82% to 88% for those with lower IQs and decreased from 37% to 13% for those with higher IQs. Collectively, almost 70% of all participants in this study were classified as either overweight or obese. Body mass index (BMI) increased throughout adulthood, especially for those with higher IQs. The steepest increase in BMI over time occurred for those with higher IQs who also took antipsychotic medications.Overall, continued risk for developing seizures, high rates of neuropsychiatric medication use, and significant and increasing rates of obesity from adolescence to adulthood underscore the importance of monitoring health issues in autistic individuals and those diagnosed with other neurodevelopmental conditions throughout the lifespan.Autistic individuals and those diagnosed with other neurodevelopmental conditions are at risk for many physical health issues from adolescence to adulthood. This includes, but is not limited to, seizure disorders, high rates of medication use, and obesity. Yet, not much longitudinal research exists measuring these health issues throughout the lifespan and, especially, in adulthood.The researchers analyzed data from a sample of 253 individuals who lived in North Carolina, Michigan, and Illinois. This sample was recruited almost 30 years ago, beginning the study when they were roughly 2 years old. Some participants had an autism spectrum disorder diagnosis, and some did not, but instead had other neurodevelopmental conditions. The researchers measured changes in medication use, height, and weight beginning in early adolescence (age 10 years) into adulthood (age 30 years). The researchers also tracked seizure occurrences across the life span (beginning at age 2 years up until age 30 years).In adulthood, this sample showed high rates of obesity and medication use. For example, almost 70% of this sample was classified as either overweight or obese. In addition, 55% of this sample was taking at least one neuropsychiatric medication in adulthood, and 22% of this sample was taking three different types of medication at the same time. Individuals with higher and lower intelligence quotient (IQs) had different findings over time: obesity increased throughout adulthood for those with higher IQs and medication use increased throughout adulthood for those with lower IQs. Seizures first developed for a group of individuals in adolescence and adulthood. Two individuals experienced their first seizure as late as 25 years of age.Research, and especially longitudinal research, on physical health in autistic adults is limited. Although we know that autistic individuals generally experience high rates of obesity, seizure disorders, and medication use, less is known about how these physical health issues change over the lifespan. This study has provided useful information regarding how certain physical health issues change over time, and who these physical health issues impact the most in adulthood.The findings in this study identified that, in adulthood, autistic adults experience high rates of physical health issues, including increasing rates of obesity and medication use for certain populations. These findings confirm how important it is for autistic adults to have access to quality health care across the lifespan. We hope that, with these findings in mind, caregivers and health professionals will work to ensure that autistic individuals, from childhood through adolescence and adulthood, will have access and assistance in monitoring these ongoing and persistent health problems.

Autistic adults are a high-risk population for suicidal thoughts and behaviors (STBs). Accordingly, this systematic review aims to review the prevalence of STBs among autistic adults, review the risk and protective factors for STBs in autistic adults, and formulate a disorder-specific conceptualization of risk in this population. We systematically searched PsycINFO and Google Scholar for all studies published prior to March 28th, 2022. We included empirical articles focused on autistic adults, ages 18 years and older, reporting on suicide-related outcomes. In total, 45 peer-reviewed empirical articles were included in the current systematic review. The most frequently studied factors in relation to suicide risk among autistic adults were interpersonal constructs (42.4% of total studies looking at risk/protective factors) and depressive symptoms (36.4% of total studies looking at risk/protective factors). We conclude by summarize two key content areas: exploring social and interpersonal constructs and better understanding the role of depressive symptoms in autism. As researchers continue to explore STBs among autistic adults, it will be necessary to addressing the overreliance on autistic symptoms instead of autism diagnoses, measurement issues of STBs, and a need for treatment adaptations.

Background Because of its centrality in the conceptualization of intellectual disability, reliable and valid measurement of adaptive behaviour is important to both research and clinical practice. The manual of the Vineland Adaptive Behavior Scales, recently released in its third edition, provides limited reliability information obtained from a sample composed primarily of typically developing individuals. The goal of this study was to evaluate the concordance of the Vineland-3 with the Vineland-II in a sample more similar in ability level to those in which the Vineland is commonly used. Methods Both editions of the Vineland Interviews were conducted with a convenience sample of 106 parents/caregivers of individuals with neurodevelopmental disability, participating at two neurodevelopmental disorder research clinics. Administrations were up to 7 days apart, but most (90%) were simultaneous. The concordance correlation coefficient (CCC) (95% confidence interval) and mean differences (95% confidence interval) were calculated for domain standard scores and subdomain v-scale scores. Results Domain-level CCC ranged from 0.78 [0.70, 0.84] (Communication) to 0.86 [0.76, 0.92] (Motor). Subdomain CCC ranged from 0.71 [0.62, 0.78] (Receptive Language) to 0.91 [0.85, 0.95] (Fine Motor). Vineland-3 scores were lower than Vineland-II scores; 77% of participants had lower Adaptive Behavior Composite scores on the Vineland-3 than on the Vineland-II. For the subdomains, the magnitude of this difference depended upon the level of adaptive behaviour. For Communication, the domain with the lowest CCC, the mean difference ranged from -13.70 [-8.03, -19.35] for a Vineland-II score or 85 to a difference of -19.18 [-12.28, -26.87] for a Vineland-II score of 40. Discussion Amongst individuals with intellectual and developmental disabilities, the Vineland-3 produces lower scores than the Vineland-II, and these clinically significant differences tend to be larger for individuals with lower levels of ability. Thus, care must be taken in interpreting scores from the Vineland-3 relative to those obtained from the previous edition.

There has been increasing attention to the assessment of minimally verbal (MV) children with autism spectrum disorder (ASD). Previous research has begun to examine the relationship between verbal abilities and emotional and behavioral problems (EBP). The current study compared parent-reported EBP in children of differing language levels on two instruments commonly used in ASD research and clinical practice, the Child Behavior Checklist (CBCL) and Aberrant Behavior Checklist (ABC). The study consisted of 1,937 6-18 years old children with ASD from the Simons Simplex Collection. Children were divided into three language groups, by ADOS module (Module 1 = MV, 2 = phrase speech (PS), and 3 = verbally fluent (VF)) and then compared on CBCL and ABC subscales. The ABC and CBCL showed different patterns of elevations across the language groups. MV children were reported to have more impairment than VF children on the ABC irritability, lethargy, and hyperactivity scales. Children with less language (MV and PS) exhibited less impairment on the CBCL internalizing domain than VF children, but did not differ on the externalizing domain. Post hoc comparisons showed that internalizing differences were driven by fewer children with less language exhibiting clinically elevated anxious/depressed scores compared to VF children. The present study underscores the significance of considering language when assessing EBP. Results have implications for the psychiatric screening of children with ASD, particularly those with language impairments. Researchers should exercise caution when applying EBP instruments designed for use with different populations and purposes to broad samples of children. Autism Res 2019, 12: 1367-1375. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Some emotional and behavioral problem (EBP) scales include items that may be inappropriate for children with ASD and limited language. The present study found that there was a tendency for children with language impairment to have lower internalizing scores on the Child Behavior Checklist, but higher scores lethargy and irritability scores on the Aberrant Behavior Checklist, relative to verbally fluent children. This suggests that each of these instruments may underestimate EBPs in certain subsets of children.

Research has documented elevated rates of co-occurring depression and anxiety in autistic adults, with some noting particularly high rates for autistic students enrolled in postsecondary education. Difficulty coping with the stressors that accompany daily life as they navigate college campuses may contribute to development or exacerbation of co-occurring conditions. Autistic students have reported that depression, anxiety and stress interfere with their success in college, but that they have difficulty identifying and accessing the supports that they need. Though many postsecondary institutions have established programs that provide academic supports to autistic students, few programs directly support mental health and wellness. Recently, stakeholders have advocated for mental health to be prioritized in adult autism research. We suggest that a specific focus on autistic students in postsecondary education is warranted and provide a brief overview of the relatively limited literature in this area. To inform development of mental health services and supports that will be both accessible and acceptable to the range of autistic students attending postsecondary education, research is recommended in four areas: factors positively and negatively affecting mental health; types of supports; outreach; on-campus training and education. It will be essential for researchers to establish community partnerships with autistic individuals to inform study design and specific research questions. This will ensure that autistic voices guide development of supports that will foster positive mental health in postsecondary education and beyond.

Individuals on the autism spectrum often have trouble with social and figurative language. As social language is often figurative, it can be challenging to disentangle the cognitive and neural sources of these difficulties. Neural systems for social cognition and language comprehension overlap in areas involved in retrieving linguistic meaning (semantics), such as the anterior temporal lobe (ATL), ventro-medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), and posterior middle temporal gyrus (pMTG). Using adjective-noun phrases, we manipulated social/nonsocial and figurative/literal dimensions, which we expected to activate distinct but overlapping regions. We hypothesized that activation differences in the group with autism (AUT) would be greater for more social and figurative stimuli. During fMRI, participants in the AUT group (N = 19) and those in the non-autistic comparison (NAC) group (N = 22) made familiarity judgments to 192 phrases in a balanced 2 × 2 (social/nonsocial x figurative/literal) design. Social phrases activated the PCC in all participants, but only the NAC group activated the vmPFC. Figurative phrases were rated as more literal by the AUT group, with the figurative-literal phrase contrast showing no activation in the AUT group, but activating the PCC and right pMTG in the NAC group. The one significant group-level neural difference was for the social-figurative condition predicted to be most different between groups: greater activation for the AUT group in the right ATL. Differences in the right ATL and pMTG in the AUT group suggest altered engagement of right homologues of the canonical semantic network being recruited for processing combined social and figurative language.

BACKGROUND: Restricted and repetitive behaviors (RRBs) are core features of autism. Factor-analytic studies comprised primarily of children have provided evidence for two domains of RRBs: Repetitive Sensory Motor (RSM) and Insistence on Sameness (IS) behaviors. The present study explores the validity of the Autism Diagnostic Interview-Revised (ADI-R) and the Repetitive Behavior Scale-Revised (RBS-R) for assessing these RRB subtypes in autistic adolescents and adults. METHODS: The sample included 293 participants (M(age)=19.89, SD=4.88 years) whose RRBs were assessed via ADI-R or RBS-R Caregiver-report or RBS-R Self-Report. Confirmatory factor analysis (CFA) was conducted to assess the validity of the two-factor structure for each instrument. Cronbach’s alpha was computed to assess subscale reliability. Correlations were examined between instrument subscales, NVIQ and age. RESULTS: Exploratory correlations were modest and provided weak evidence in favor of the utility of a CFA for the ADI-R. The RBS-R Caregiver and Self-Report CFA and internal consistencies supported the two-factor RSM and IS model tested. Consistent with previous literature, NVIQ was negatively correlated with the RBS-R Caregiver RSM subscale, but not meaningfully associated with IS. Neither RBS-R Self-Report subscale were meaningfully correlated with NVIQ. Across instruments, RSM subscales were correlated, but associations between IS were minimal. CONCLUSIONS: The present study provides initial support for the use of the RBS-R Caregiver and Self-Report to measure dimensions of RSM and IS behaviors in autistic adolescents and adults. The present data did not support the use of the ADI-R to assess these RRB subtypes in older individuals. Conclusions must be interpreted cautiously in light of the present study’s sample limitations. Additional research is needed to understand differences in caregiver and self-reported RRBs. Further research on RRBs in autistic adolescents and adults, particularly in samples of greater gender and racial/ethnic diversity, is critical to inform community understanding and knowledge of autism in adulthood.

In "The Need for a Clinically Useful Schema of Social Communication," Blank etal. present an observation and coding method (The Initiating, Responding, Expectancy Violations [IREV] schema) for identifying "expectancy violations (EVs)," which may signal clinically significant departures from normal social communication behavior (eg, in individuals with autism spectrum disorder [ASD]).1 The authors point out that "historically, observation of a patient's (social communication) has not been part of the routine psychiatric mental status examination," and argue that this is an important missed opportunity for clinicians. Several direct observation methods exist for identifying and/or monitoring changes in social communication deficits associated with ASD.2 Despite their established diagnostic validity, it remains true that these measures used in isolation will result in a relatively high rate of "false positives"-usually comprising children who are better described with other diagnoses (eg, intellectual disability, language disorder, attention-deficit/hyperactivity disorder [ADHD]).2 This underscores the critical importance of context when interpreting observed social communication deficits.

The autism spectrum disorder (ASD) research community is increasingly considering the importance of measuring outcomes that are meaningful to individuals with ASD and their families. The 2017 IMFAR preconference aimed to gain the perspectives of how to define and measure "meaningful outcomes" from 280 participants, including people with ASD and their families, service providers, and researchers. Six themes were identified: (a) the definition of "outcome" varies by context and perspective; (b) the need to broaden the scope of what researchers measure; (c) the need for new assessment tools; (d) the need to expand data analytic methods; (e) where to focus (with emphasis on considering different developmental stages and aspects of diversity); and (f) a need for community partnerships to bridge research and daily practice. The challenge that the research community now faces is how to move the evidence base for clinical practice forward while keeping alive the divergence of views and considerations that are relevant for thinking about complex outcomes for the highly heterogeneous group of individuals with ASD. This commentary provides recommendations, with an emphasis on lifespan viewpoints that encompass individual strengths and preferences. Autism Research 2018, 11: 1446-1454. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The 2017 IMFAR preconference aimed to gain the perspectives of how to define and measure "meaningful outcomes" from a variety of stakeholders. This commentary outlines the six themes identified from keynote and panel presentations and audience-participated discussions. Recommendations are made to emphasize perspectives that look across the lifespan and encompass individual strengths and preferences.

The original version of the article has contained an error in Table 3 (the organization of Module 2 items into the Basic Social Communication and Interaction Quality factors was incorrect). The updated table is given below and it shows the correct organization (7 Basic and 3 Interaction Quality items).

Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent-reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD-associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non-verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parent-report of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2018, 11: 175-184. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay summary This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non-verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD.

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.

BACKGROUND: Studies estimate that 30% of individuals with autism are minimally verbal. Understanding what factors predict longer-term expressive development in children with language delays is critical to inform identification and treatment of those at-risk for persistent language impairments. The present study examined predictors of expressive language development in language-delayed preschoolers followed through later school-age and young adulthood. METHODS: Children using single words or less on the Autism Diagnostic Observation Schedule (ADOS) at approximately 3 years old were drawn from the Early Diagnosis (EDX) and Pathways in ASD longitudinal cohorts. Age-3 predictors of Age-19 ADOS language level were identified using Classification and Regression Trees (CART) in the EDX sample. Linear mixed models examined the effects of CART-identified predictors on Vineland expressive communication (VExp) trajectories from Age-3 to Age-19. The same linear mixed models were examined in the Pathways sample, identifying predictors of VExp from ages 3 to 10.5 years. RESULTS: Significantly delayed fine motor skills (T-score < 20) was the strongest CART predictor of Age-19 language. In the linear mixed models, time, Age-3 fine motor skills and initiation of joint attention (IJA) predicted VExp trajectories in the EDX sample, even when controlling for Age-3 visual receptive abilities. In the Pathways sample, time and Age-3 fine motor skills were significant predictors of VExp trajectories; IJA and cognitive skills were not significant predictors. CONCLUSIONS: Marked deficits in fine motor skills may be a salient proxy marker for identifying language-delayed children with ASD who are at risk for persistent language impairments. This finding adds to the literature demonstrating a relation between motor and language development in ASD. Investigating individual skill areas (e.g., fine motor and nonverbal problem-solving skills), rather than broader indices of developmental level (e.g., nonverbal IQ) may provide important cues to understanding longer-term language outcomes that can be targeted in early intervention.

This study assessed the utility of a brief assessment (the Peabody Picture Vocabulary Test-4th Edition; PPVT4) as a proxy for verbal IQ (VIQ) in large-scale studies of autism spectrum disorder (ASD). In a sample of 2,420 proband with ASD, PPVT4:IQ correlations were strong. PPVT4 scores were, on average, 5.46 points higher than VIQ; 79% of children had PPVT4 scores within one standard deviation (+/-15) of their VIQ and 90% were similarly classified as having abilities above or below 70 on both measures. Distributions of PPVT4 and VIQ by de novo mutation status were highly similar. These results strongly support the utility of PPVT4 as a proxy for VIQ in large-scale ASD studies, particularly for genetic investigations.

Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium - Collaborators (162): Anney RJL, Ripke S, Anttila V, Grove J, Holmans P, Huang H, Klei L, Lee PH, Medland SE, Neale B, Robinson E, Weiss LA, Zwaigenbaum L, Yu TW, Wittemeyer K, Willsey AJ, Wijsman EM, Werge T, Wassink TH, Waltes R, Walsh CA, Wallace S, Vorstman JAS, Vieland VJ, Vicente AM, vanEngeland H, Tsang K, Thompson AP, Szatmari P, Svantesson O, Steinberg S, Stefansson K, Stefansson H, State MW, Soorya L, Silagadze T, Scherer SW, Schellenberg GD, Sandin S, Sanders SJ, Saemundsen E, Rouleau GA, Rogé B, Roeder K, Roberts W, Reichert J, Reichenberg A, Rehnström K, Regan R, Poustka F, Poultney CS, Piven J, Pinto D, Pericak-Vance MA, Pejovic-Milovancevic M, Pedersen MG, Pedersen CB, Paterson AD, Parr JR, Pagnamenta AT, Oliveira G, Nurnberger JI, Nordentoft M, Murtha MT, Mouga S, Mortensen PB, Mors O, Morrow EM, Moreno-De-Luca D, Monaco AP, Minshew N, Merikangas A, McMahon WM, McGrew SG, Mattheisen M, Martsenkovsky I, Martin DM, Mane SM, Magnusson P, Magalhaes T, Maestrini E, Lowe JK, Lord C, Levitt P, Martin CL, Ledbetter DH, Leboyer M, LeCouteur AS, Ladd-Acosta C, Kolevzon A, Klauck SM, Jacob S, Iliadou B, Hultman CM, Hougaard DM, Hertz-Picciotto I, Hendren R, Hansen CS, Haines JL, Guter SJ, Grice DE, Green JM, Green A, Goldberg AP, Gillberg C, Gilbert J, Gallagher L, Freitag CM, Fombonne E, Folstein SE, Fernandez B, Fallin MD, Ercan-Sencicek AG, Ennis S, Duque F, Duketis E, Delorme R, DeRubeis S, DeJonge MV, Dawson G, Cuccaro ML, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Celestino-Soper PBS, Casey J, Cantor RM, Café C, Bybjerg-Grauholm J, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bolshakova N, Betancur C, Bernier R, Beaudet AL, Battaglia A, Bal VH, Baird G, Bailey AJ, Bækvad-Hansen M, Bader JS, Bacchelli E, Anagnostou E, Amaral D, Almeida J, Børglum AD, Buxbaum JD, Chakravarti A, Cook EH, Coon H, Geschwind DH, Gill M, Hallmayer J, Palotie A, Santangelo S, Sutcliffe JS, Arking DE, Devlin B, Daly MJ. Astrid M. Vicente .- Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis do INSA. PMS free full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441062/ Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR)

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.

The autism spectrum disorder (ASD) research community is increasingly considering the importance of measuring outcomes that are meaningful to individuals with ASD and their families. The 2017 IMFAR preconference aimed to gain the perspectives of how to define and measure "meaningful outcomes" from 280 participants, including people with ASD and their families, service providers, and researchers. Six themes were identified: (a) the definition of "outcome" varies by context and perspective; (b) the need to broaden the scope of what researchers measure; (c) the need for new assessment tools; (d) the need to expand data analytic methods; (e) where to focus (with emphasis on considering different developmental stages and aspects of diversity); and (f) a need for community partnerships to bridge research and daily practice. The challenge that the research community now faces is how to move the evidence base for clinical practice forward while keeping alive the divergence of views and considerations that are relevant for thinking about complex outcomes for the highly heterogeneous group of individuals with ASD. This commentary provides recommendations, with an emphasis on lifespan viewpoints that encompass individual strengths and preferences. Autism Research 2018, 11: 1446-1454. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The 2017 IMFAR preconference aimed to gain the perspectives of how to define and measure "meaningful outcomes" from a variety of stakeholders. This commentary outlines the six themes identified from keynote and panel presentations and audience-participated discussions. Recommendations are made to emphasize perspectives that look across the lifespan and encompass individual strengths and preferences.

Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1). Through analysis of de novo mutations in autism spectrum disorder (ASD), Sanders et al. find that small deletions, but not large deletions/duplications, contain one critical gene. Combining CNV and sequencing data, they identify 6 loci and 65 genes associated with ASD.

This study explored change in social-communicative symptoms in 140 individuals with childhood autism spectrum disorder (ASD) diagnoses. Trajectories of caregiver-reported social-communicative symptoms were examined for three groups (verbal, delayed speech, minimally verbal) from ages 2 to 19 years. Groups showed comparable levels of social-communicative impairment at 2 years and significant decreases in overall symptom levels across the 17-year period (P.001). Across three subdomains, main effects of time and language (P.001) reflected patterns of overall improvement, although children with more impaired language tended to have more caregiver-reported symptoms relative to verbal peers. A significant time-by-language interaction (P.001) reflected that trajectories of socioemotional reciprocity symptoms differed according to patterns of language development. In contrast, improvements in the nonverbal communication domain were seen across language groups, whereas deficits in the development and maintenance of relationships improved for only verbal children. Verbal adults showed significant reductions in the prevalence of kseveral symptoms exhibited during childhood. Improvements suggest that symptoms indicative of ASD in young children may no longer be diagnostic markers in adolescents and adults. Relative stability of several items suggests that impaired facial expression may be a core ASD symptom that warrants more systematic study across the lifespan. Research investigating the manifestation of ASD in older individuals is needed to foster development of appropriate assessment tools and interventions. Differential relationships to developmental factors within the broader social-communication domain underscores a need to focus on more narrowly defined symptom constructs when exploring links between pathophysiology and observable phenotypes. Autism Research 2019, 12: 89-99. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In a sample of 140 participants with autism spectrum disorder (ASD) followed from 2 to 19 years old, this study found that overall social-communicative symptoms improve across childhood and adolescence. However, timing and amount of change varied for different symptom categories and participants with different language abilities. Findings suggest that some older adolescents and adults with ASD may not exhibit the same difficulties observed in young children with ASD. More research is needed to better understand the strengths and needs of young adults with ASD.

Raw totals from diagnostic and screening measures for autism spectrum disorder (ASD) are frequently used as dimensional measures of autism symptom severity without appropriate correction for confounding factors, such as developmental level or non-ASD-specific behavior problems. Although these associated features are important to consider when diagnosing ASD and developing intervention plans, both researchers and clinicians sometimes need metrics of ASD severity that are not influenced by these factors. The Autism Diagnostic Observation Schedule (ADOS) domain calibrated severity scores (CSS) were created to provide separate estimates of social affect (SA-CSS) and restricted, repetitive behaviors (RRB-CSS) that are relatively independent of child characteristics (Hus et al., 2014). Using a sample of 2,509 probands with ASD from the Simons Simplex Collection (SSC), this study provides the first replication of the ADOS domain CSS in an independent sample. Consistent with the original standardization study, when applied to existing SSC data, the ADOS domain CSS were less influenced by age and cognitive ability compared to raw domain totals. Domain CSS were also relatively independent of behavior problems. Use of the ADOS domain CSS to assess relationships between ASD symptoms and genetic risk factors will increase confidence that associations reflect domain-specific relationships. Scores also offer less developmentally-influenced estimates of ASD severity for future phenotypic explorations in the SSC. This independent replication provides support for the application of the ADOS domain CSS in other samples, though further replication in population-based samples will be an important next step.

Objective This study examined early predictors of and changes in school-age academic achievement and class placement in children referred for autism spectrum disorder (ASD) at age 2. Method Of 111 ASD referrals, 74 were diagnosed with ASD at age 18. Regression analyses were performed to identify age 3 predictors of achievement in arithmetic, passage comprehension, word reading, and spelling at ages 9 and 18. Linear Mixed Models were used to examine predictors of academic growth between ages 9 and 18. Results Academic skills varied widely at 9 and 18, but were mostly commensurate with or higher than expected given cognitive levels. However, 22% (age 9) and 32% (age 18) of children with average/above average IQ showed below/low average achievement in at least one academic domain. Children who remained in general education/inclusion classrooms had higher achievement than those who moved to special education classrooms. Stronger cognitive skills at age 3 and 9 predicted better academic achievement and faster academic growth from age 9 to 18. Parent participation in intervention by age 3 predicted better achievement at age 9 and 18. Conclusions Many children with ASD achieve basic academic skills commensurate with or higher than their cognitive ability. However, more rigorous screening for learning difficulties may be important for those with average cognitive skills because a significant minority show relative academic delays. Interventions targeting cognitive skills and parent participation in early treatment may have cascading effects on long-term academic development.

OBJECTIVE: Aside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). The objective of this study was to extend work in the Simons Simplex Collection by comparing the phenotypic profiles of ASD probands with or without identified de novo loss of function mutations or copy number variants in high-confidence ASD-associated genes or loci.METHOD: Analyses preemptively accounted for documented differences in sex and IQ in affected individuals with de novo mutations by matching probands with and without these genetic events on sex, IQ, and age before comparing them on multiple behavioral domains.RESULTS: Children with de novo mutations (N=112) had a greater likelihood of motor delay during early development (later age at walking), but they were less impaired on certain measures of ASD core symptoms (parent-rated social communication abnormalities and clinician-rated diagnostic certainty about ASD) in later childhood. These children also showed relative strengths in verbal and language abilities, including a smaller discrepancy between nonverbal and verbal IQ and a greater likelihood of having achieved fluent language (i.e., regular use of complex sentences).CONCLUSIONS: Children with ASD with de novo mutations may exhibit a "muted" symptom profile with respect to social communication and language deficits relative to those with ASD with no identified genetic abnormalities. Such findings suggest that examining early milestone differences and standardized testing results may be helpful in etiologic efforts, and potentially in clinical differentiation of various subtypes of ASD, but only if developmental and demographic variables are properly accounted for first.

Summary: Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0–2.7; p = 0.03), are more common in female probands (p = 0.02), are enriched among genes encoding FMRP targets (p = 6 × 10−9), and arise predominantly on the paternal chromosome (p < 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. : Insertions and deletions (indels) have proven especially difficult to detect in exome sequencing data. Dong et al. now identify indels in exome data for 787 autism spectrum disorder (ASD) families. They demonstrate association between de novo indels that alter the reading frame and ASD. Furthermore, by observing clustering of indels in unrelated probands, they uncover two additional ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.

Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent-reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD-associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non-verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parent-report of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2018, 11: 175-184. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non-verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD.

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.

Objective This study examined variability in autism symptom trajectories in toddlers referred for possible autism spectrum disorder (ASD) who had frequent observations from 14 to 36 months of age. Method In total, 912 observations of the Autism Diagnostic Observation Schedule (ADOS) were obtained from 149 children (103 with ASD) followed from 14 to 36 months of age. As a follow-up to a previous analysis of ADOS algorithm scores, a different analytic approach (Proc Traj) was implemented to identify several courses of symptom trajectories using ADOS Calibrated Severity Scores in a larger sample. Proc Traj is a statistical method that clusters individuals into separate groups based on different growth trajectories. Changes in symptom severity based on individual ADOS items also were examined. Results Trajectory analysis of overall symptom severity identified 4 clusters (non-spectrum ∼25%; worsening ∼27%; moderately-improving ∼25%; severe-persistent ∼23%). Trajectory clusters varied significantly in the proportions of confirmatory ASD diagnosis, level of baseline and final verbal and nonverbal abilities, and symptom severity. For the moderately-improving group, social communication improved, whereas restricted and repetitive behaviors were stable over time. Language and verbal and nonverbal communication improved for many children, but several social affect and restricted and repetitive behavior symptoms remained stable or worsened. Conclusion Significant variability in symptom trajectories was observed among toddlers referred for possible ASD. Changes in social and restricted and repetitive behavior domain scores did not always co-occur. Similarly, item-level trajectories did not always align with trajectories of overall severity scores. These findings highlight the importance of monitoring individual symptoms within broader symptom domains when conducting repeated assessments for young children with suspected ASD.

Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised algorithm demonstrated increased sensitivity, but lower specificity in the overall sample. Estimates were highest for females, individuals with a verbal IQ below 85 or above 115, and ages 16 and older. Best practice diagnostic procedures should include the Module 4 in conjunction with other assessment tools. Balancing needs for sensitivity and specificity depending on the purpose of assessment (e.g., clinical vs. research) and demographic characteristics mentioned above will enhance its utility.

Standardized calibrated severity scores (CSS) have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Modules 1–4 as a metric of the relative severity of autism-specific behaviors. Total and domain CSS were created for the Toddler Module to facilitate comparison to other modules. Analyses included 388 children with ASD age 12 to 30 months and were replicated on 435 repeated assessments from 127 children with ASD. Compared to raw scores, associations between total and domain CSS and participant characteristics were reduced in the original sample. Verbal IQ effects on Social Affect-CSS were not reduced in the replication sample. Toddler Module CSS increases comparability of ADOS-2 scores across modules and allows studies of symptom trajectories to extend to earlier ages.

Daily living skills (DLS), such as personal hygiene, meal preparation, and money management, are important to independent living. Research suggests that many individuals with autism spectrum disorder exhibit impairments in daily living skills relative to their cognitive skills. This study examined predictors of daily living skills attainment and trajectories of daily living skills in a longitudinal sample referred for possible autism spectrum disorder and followed from 2 to 21 years of age. Consistent with previous studies, participants with autism spectrum disorder and nonspectrum diagnoses showed continual development of daily living skills throughout childhood and adolescence. Early childhood nonverbal mental age was the strongest predictor of daily living skills attainment for both diagnostic groups. Group-based modeling suggested two distinct trajectories of daily living skills development for participants with autism spectrum disorder. Skill levels for both groups of young adults with autism spectrum disorder remained considerably below age level expectations. Whereas the “High-DLS” group gained approximately 12 years in daily living skills from T2 to T21, the “Low-DLS” group’s daily living skills improved 3–4 years over the 16- to 19-year study period. Nonverbal mental age, receptive language, and social-communication impairment at 2 years predicted High- versus Low-DLS group membership. Receiving greater than 20 h of parent-implemented intervention before age 3 was also associated with daily living skills trajectory. Results suggest that daily living skills should be a focus of treatment plans for individuals with autism spectrum disorder, particularly adolescents transitioning to young adulthood.

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.