Publications by authors named "Stelios Georgiades"

71 Publications

Association of Child and Family Attributes With Outcomes in Children With Autism.

JAMA Netw Open 2021 Mar 1;4(3):e212530. Epub 2021 Mar 1.

University of Alberta, Edmonton, Alberta, Canada.

Importance: The prevalence and attributes of positive outcomes (or doing well) among children with autism spectrum disorder (ASD) in midchildhood are not well known.

Objective: To estimate the prevalence of doing well according to metrics of proficiency and growth and to investigate the extent to which significant associations exist between child- and family-level variables and doing well.

Design, Setting, And Participants: This longitudinal cohort study included children with ASD from regional clinics across Canada. Participants were sampled 3 times between ages 2 and 4.9 years (T1) and twice in follow-up into middle childhood (T2). Data were analyzed March 2018 through January 2020.

Exposures: Language and IQ assessments at first sample; household income, parent coping, and family functioning.

Main Outcomes And Measures: Key outcome domains of developmental health included measures of socialization, communication, independent living skills, and measures of internalizing and externalizing behaviors. Thresholds for doing well in these domains by either proficiency or growth were established. The extent to which language, IQ, household income, parent coping, and family functioning were associated with assessed outcomes was determined by logistic regression. The association between outcomes and concurrent Autism Diagnostic Observation Schedule (ADOS) classification scores was also estimated.

Results: In a total cohort of 272 children (234 [86.0%] boys; mean [SD] age, 10.76 [0.26] years), approximately 78.8% (95% CI, 73.2%-84.4%) of the sample were estimated to be doing well by either metric on at least 1 domain, and 23.6% (95% CI, 17.7%-29.4%) were doing well in 4 or 5 domains. It was possible to be doing well by either proficiency or growth and still meet ADOS criteria for ASD. For the growth metric, between 61.5% (95% CI, 40.7%-79.1%) and 79.6% (95% CI, 66.0%-88.9%) of participants had ADOS scores of 4 or greater; for the proficiency metric, between 63.8% (95% CI, 48.4%-76.9%) and 75.8% (95% CI, 63.0%-85.4%) had scores of 4 or greater. Doing well by either metric for all domains was associated with T1 scores on that outcome domain (eg, T1 daily living skills associated with doing well at T2 daily living by the proficiency metric as measured by the Vineland Adaptive Behavior Scales-Second Edition daily living skills scale [202 participants]: β = 0.07; OR, 1.07; 95% CI, 1.03-1.11; P < .001). Doing well in socialization by the growth metric was also associated with better T1 language skills scores (202 participants) (β = 0.04; OR, 1.04; 95% CI, 1.00-1.07, P = .04). Doing well in externalizing by the growth metric was also associated with higher household income at T1 (178 participants) (β = 0.10; OR, 1.10; 95% CI, 1.06-1.15; P < .001). Better family functioning at T1 was associated with doing well on both socialization and externalizing by proficiency metric and on internalizing by growth metric (socialization by proficiency [202 participants]: β = -1.01; OR, 0.36; 95% CI, 0.14-0.93; P = .04; externalizing by proficiency [178 participants]: β = 1.00; OR, 0.37; 95% CI, 0.16-0.82; P = .02; internalizing by growth [178 participants]: β = -1.03; OR, 0.36; 95% CI, 0.16-0.79; P = .01).

Conclusions And Relevance: This cohort study found that a substantial proportion of children with ASD were doing well by middle childhood in at least 1 key domain of developmental health, and that doing well was possible even in the context of continuing to meet criteria for ASD. These results support a strengths-based approach to treatment planning that should include robust support for families to increase the potential likelihood of doing well later in life.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.2530DOI Listing
March 2021

Trajectories of Symptom Severity in Children with Autism: Variability and Turning Points through the Transition to School.

J Autism Dev Disord 2021 Mar 11. Epub 2021 Mar 11.

Centre for Addition and Mental Health, Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, The Hospital for Sick Children, Toronto, Canada.

This study examined the trajectories of autistic symptom severity in an inception cohort of 187 children with ASD assessed across four time points from diagnosis to age 10. Trajectory groups were derived using multivariate cluster analysis. A two trajectory/cluster solution was selected. Change in trajectory slopes revealed a turning point marked by plateauing in symptom reduction during the period of transition to school (age 6) for one of the two trajectories. Trajectories were labelled: Continuously Improving (27%) and Improving then Plateauing (73% of sample). Children in the two trajectories differed in levels of symptom severity, language, cognitive, and adaptive functioning skills. Study findings can inform the development of more personalized services for children with ASD transitioning into the school system.
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http://dx.doi.org/10.1007/s10803-021-04949-2DOI Listing
March 2021

"Best Things": Parents Describe Their Children with Autism Spectrum Disorder Over Time.

J Autism Dev Disord 2021 Feb 2. Epub 2021 Feb 2.

University of Ottawa, Ottawa, ON, Canada.

This study examined parental perceptions of the character traits of children with autism from early childhood to age 11. Parents (n = 153) provided descriptions of the "best things" about their children on the Child Behavior Checklist (CBCL) at ages 3-4, 7-8, and 10-11 years. Descriptions were coded using the framework of the Values in Action Classification of Strengths, with additional traits added as needed. Parent-endorsed traits included love, kindness, happiness, and humor in children across all ages and traits such as perseverance as children entered school. Higher CBCL scores were associated with a lower likelihood of endorsement for Humanity traits. Results are congruent with a contemporary neurodiversity perspective that emphasizes strengths and resilience.
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http://dx.doi.org/10.1007/s10803-021-04890-4DOI Listing
February 2021

DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders.

J Autism Dev Disord 2021 Jan 4. Epub 2021 Jan 4.

Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.

Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes.
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http://dx.doi.org/10.1007/s10803-020-04792-xDOI Listing
January 2021

Factor Structure of Repetitive Behaviors Across Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

J Autism Dev Disord 2020 Nov 24. Epub 2020 Nov 24.

Department of Psychology, Western University, London, ON, Canada.

Restricted interests and repetitive behaviors (RRBs) are core symptoms of autism spectrum disorder (ASD), and commonly occur in attention-deficit/hyperactivity disorder (ADHD). Little is known about how RRBs manifest in ADHD. We quantified and compared factor structures of RRBs in children with ASD (n = 634) or ADHD (n = 448), and related factors to sex and IQ. A four-factor solution emerged, including Stereotypy, Self-Injury, Compulsions, and Ritualistic/Sameness. Factor structures were equivalent across diagnoses, though symptoms were more severe in ASD. IQ negatively correlated with Stereotypy, Self-Injury, and Compulsions in ASD, and negatively correlated with Compulsions and Ritualistic/Sameness behaviors in ADHD. In ASD only, females exhibited higher Self-Injury. Thus, patterns of RRBs are preserved across ASD and ADHD, but severity and relationship with IQ differed.
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http://dx.doi.org/10.1007/s10803-020-04800-0DOI Listing
November 2020

Sex Differences in Age of Diagnosis and First Concern among Children with Autism Spectrum Disorder.

J Clin Child Adolesc Psychol 2020 Nov 2:1-11. Epub 2020 Nov 2.

Department of Psychiatry, Western University.

Objective: Early identification of autism spectrum disorder (ASD) is an essential healthcare priority. Girls may be at risk for late diagnosis, although research is equivocal regarding how sex and other factors relate to ASD identification. The goals of the current investigation were to (1) identify how child sex, cognitive abilities, and demographic factors relate to age of first concern (AOC) and age of diagnosis (AOD), (2) evaluate trends in AOC/AOD over time, and (3) consider whether main effects of sex on AOC/AOD are moderated by cognitive abilities or time.

Method: Children (N = 365; 20% female; 85.6% identified as White) with ASD participated through the Province of Ontario Neurodevelopmental Disorders (POND) Network. Study records included AOD, date/timing of diagnosis (between 1996 and 2017), age of first parent concern, demographics, and standardized cognitive testing results (24.7% of children had IQ scores below standard scores of 70).

Results: Average AOC occurred before 2 years of age whereas average AOD occurred after 5 years of age. Girls did not differ on AOC but had a later AOD than boys. Higher verbal IQ was associated with later AOD more strongly in girls than boys. Regarding time-related changes, average AOC and AOD increased across the study period, more strongly for girls.

Conclusions: Results support that sex is a key factor underlying delays in ASD identification and highlight the urgent need to improve diagnostic practices among girls. Limitations and implications for improving the diagnostic process are discussed.

ASD=autism spectrum disorder; IQ=intelligence quotient; AOC=parental report of age of first concern; AOD=age of diagnosis.
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http://dx.doi.org/10.1080/15374416.2020.1823850DOI Listing
November 2020

Dr. Bishop et al. Reply.

J Am Acad Child Adolesc Psychiatry 2020 11;59(11):1200-1202

Pediatrics & Developmental Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland.

In "The Need for a Clinically Useful Schema of Social Communication," Blank et al. 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]). 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. 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]). This underscores the critical importance of context when interpreting observed social communication deficits.
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http://dx.doi.org/10.1016/j.jaac.2020.07.006DOI Listing
November 2020

Extracting Latent Subdimensions of Social Communication: A Cross-Measure Factor Analysis.

J Am Acad Child Adolesc Psychiatry 2020 Oct 4. Epub 2020 Oct 4.

UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA.

Objective: Social communication deficits associated with autism spectrum disorder (ASD) are commonly represented as a single behavioral domain. However, increased precision of measurement of social communication is needed to promote more nuanced phenotyping, both within the autism spectrum and across diagnostic boundaries.

Method: A large sample (N = 1,470) of 4- to 10-year-old children was aggregated from across 4 data sources, and then randomly split into testing and validation samples. A total of 57 selected social communication items from 3 widely used autism symptom measures (the Autism Diagnostic Observation Scale [ADOS], Autism Diagnostic Interview-Revised [ADI-R], and Social Responsiveness Scale [SRS]) were analyzed in the multi-trait/multi-method factor analysis framework. The selected model was then confirmed with the validation sample.

Results: The 4-substantive factor model, with 3 orthogonal method factors, was selected using the testing sample based on fit indices and then confirmed with the validation sample. Two of the factors, "Basic Social Communication Skills" and "Interaction Quality," were similar to those identified in a previous analysis of the ADOS, Module 3. Two additional factors, "Peer Interaction and Modification of Behavior" and "Social Initiation and Affiliation," also emerged. Factor scores showed nominal correlations with age and verbal IQ.

Conclusion: Identification of subdimensions could inform the creation of better conceptual models of social communication impairments, including mapping of how the cascading effects of social communication deficits unfold in ASD versus other disorders. Especially if extended to include both older and younger age cohorts and individuals with more varying developmental levels, these efforts could inform phenotype-based exploration for biological and genetic mechanisms by pinpointing specific mechanisms that contribute to various types of social communication deficits.
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http://dx.doi.org/10.1016/j.jaac.2020.08.444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019433PMC
October 2020

Concurrent Validity of the ABAS-II Questionnaire with the Vineland II Interview for Adaptive Behavior in a Pediatric ASD Sample: High Correspondence Despite Systematically Lower Scores.

J Autism Dev Disord 2020 Aug 10. Epub 2020 Aug 10.

Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

We examined the correlation between interviewer-administered Vineland Adaptive Behavior Scale II (VABS-II) and the parent-rated Adaptive Behavior Assessment System II (ABAS-II) questionnaire in 352 participants (ages 1.5-20.8 years) with autism spectrum disorder (ASD) to determine if ABAS could be used as a screen to reduce the number of VABS interviews. Corresponding domain scores between the two measures were highly correlated but scores were significantly lower on the ABAS-II. Screening with ABAS-II significantly reduced the number of VABS-II interviews required with little cost to overall accuracy. The ABAS-II provides a cost- and time-saving alternative to the VABS-II to rule out functional impairment; however, scores are not strictly comparable between the two measures.
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http://dx.doi.org/10.1007/s10803-020-04597-yDOI Listing
August 2020

Co-occurring trajectories of anxiety and insistence on sameness behaviour in autism spectrum disorder.

Br J Psychiatry 2021 Jan;218(1):20-27

Centre for Addiction and Mental Health; and The Hospital for Sick Children; and Department of Psychiatry, University of Toronto, Toronto, Canada.

Background: Children with autism spectrum disorder (ASD) have increased susceptibility to anxiety disorders. Variation in a common ASD symptom, insistence on sameness behaviour, may predict future anxiety symptoms.

Aims: To describe the joint heterogeneous longitudinal trajectories of insistence on sameness and anxiety in children with ASD and to characterise subgroups at higher risk for anxiety.

Method: In a longitudinal ASD cohort (n = 421), insistence on sameness behaviour was measured using the Autism Diagnostic Interview-Revised at approximately ages 3, 6 and 11 years. Anxiety was quantified at 8 time points between ages 3 and 11 years using the Child Behavior Checklist (CBCL) (parent report). Clusters of participants following similar trajectories were identified using group-based and joint trajectory modelling.

Results: Three insistence on sameness trajectories were identified: (a) 'low-stable' (41.7% of participants), (b) 'moderate-increasing' (52.0%) and (c) 'high-peaking' (i.e. increasing then stabilising/decreasing behaviour) (6.3%). Four anxiety trajectories were identified: (a) 'low-increasing' (51.0%), (b) 'moderate-decreasing' (16.2%), (c) 'moderate-increasing' (19.6%) and (d) 'high-stable' (13.1%). Of those assigned to the 'high-peaking' insistence on sameness trajectory, 95% jointly followed an anxiety trajectory that surpassed the threshold for clinical concern (T-score >65) by middle childhood (anxiety trajectories 3 or 4). Insistence on sameness and anxiety trajectories were similar in severity and direction for 64% of the sample; for 36%, incongruous patterns were seen (e.g. decreasing anxiety and increasing insistence on sameness).

Conclusions: The concurrent assessment of insistence on sameness behaviour and anxiety in ASD may help in understanding current symptom profiles and anticipating future trajectories. High preschool insistence on sameness in particular may be associated with elevated current or future anxiety symptoms.
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http://dx.doi.org/10.1192/bjp.2020.127DOI Listing
January 2021

Temperament influences the relationship between symptom severity and adaptive functioning in children with autism spectrum disorder.

Autism 2020 11 2;24(8):2057-2070. Epub 2020 Jul 2.

McMaster University, Canada.

Lay Abstract: Temperament is often thought of as behavioural traits that are relatively stable over time but can vary between individuals. Children diagnosed with autism spectrum disorder are often characterized as having 'reactive' and 'negative' temperaments when compared to same-aged peers with or without disabilities, which can negatively impact the development of adaptive functioning skills but little is known about variations of temperament between individual children diagnosed with autism spectrum disorder. This study aimed to (a) explore the variation of individual temperament traits within a sample of school-aged children with autism spectrum disorder to determine whether subgroups with similar trait profiles emerge and (b) examine whether temperament influences the relationship between autism symptoms and adaptive functioning outcomes. Results from our dataset suggest that children diagnosed with autism spectrum disorder fit under two profiles: 'even' and 'reactive'. Furthermore, our analysis shows that temperament can influence the impact of increasing symptom severity on adaptive functioning skills in children with autism spectrum disorder. Study findings highlight the importance of considering temperament when trying to understand the individual differences that influence the development of functioning and developmental outcomes in children with autism spectrum disorder.
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http://dx.doi.org/10.1177/1362361320933048DOI Listing
November 2020

Teacher-Reported Prevalence of FASD in Kindergarten in Canada: Association with Child Development and Problems at Home.

J Autism Dev Disord 2021 Feb;51(2):433-443

Offord Centre for Child Studies, Department of Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, ON, Canada.

The prevalence of Fetal Alcohol Spectrum Disorder (FASD) may be underestimated as it can be difficult to diagnose in early childhood possibly reflecting unique developmental trajectories relative to other Neurodevelopmental Disabilities (NDDs). Using data collected via the Early Development Instrument (EDI) between 2010 and 2015, we examined the prevalence of kindergarten children with FASD and their concurrent developmental outcomes. We found that the prevalence of FASD ranged from 0.01 to 0.31%. A greater percentage of children with FASD had teacher-reported home problems that interfered with their classroom functioning. Overall children with FASD had higher mean scores on the developmental domains compared to children with NDDs. Results of the current study can inform strategies and policies for early identification and intervention.
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http://dx.doi.org/10.1007/s10803-020-04545-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835185PMC
February 2021

Inattention and hyperactive/impulsive component scores do not differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder in a clinical sample.

Mol Autism 2020 04 25;11(1):28. Epub 2020 Apr 25.

Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.

Background: Although there is high co-occurrence between ASD and ADHD, the nature of this co-occurrence remains unclear. Our study aimed to examine the underlying relationship between ASD and ADHD symptoms in a combined sample of children with a primary clinical diagnosis of ASD or ADHD.

Methods: Participants included children and youth (aged 3-20 years) with a clinical diagnosis of ASD (n = 303) or ADHD (n = 319) for a total of 622 participants. Parents of these children completed the social communication questionnaire (SCQ), a measure of autism symptoms, and the strengths and weaknesses of ADHD and normal behavior (SWAN) questionnaire, a measure of ADHD symptoms. A principal component analysis (PCA) was performed on combined SCQ and SWAN items, followed by a profile analysis comparing normalized component scores between diagnostic groups and gender.

Results: PCA revealed a four-component solution (inattention, hyperactivity/impulsivity, social-communication, and restricted, repetitive, behaviors, and interests (RRBI)), with no overlap between SCQ and SWAN items in the components. Children with ASD had higher component scores in social-communication and RRBI than children with ADHD, while there was no difference in inattentive and hyperactive/impulsive scores between diagnostic groups. Males had higher scores than females in social-communication, RRBI, and hyperactivity/impulsivity components in each diagnostic group.

Limitations: We did not formally assess children with ASD for ADHD using our research-criteria for ADHD, and vice versa. High rates of co-occurring ADHD in ASD, for example, may have inflated component scores in inattention and hyperactivity/impulsivity. A disadvantage with using single informant-based reports (i.e., parent-rated questionnaires) is that ASD and ADHD symptoms may be difficult to distinguish by parents, and may be interpreted differently between parents and clinicians.

Conclusions: ASD and ADHD items loaded on separate components in our sample, suggesting that the measurement structure cannot explain the covariation between the two disorders in clinical samples. High levels of inattention and hyperactivity/impulsivity were seen in both ASD and ADHD in our clinical sample. This supports the need for a dimensional framework that examines neurodevelopmental domains across traditional diagnostic boundaries. Females also had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity than males, suggesting that there may be gender-specific phenotypes related to the two conditions.
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http://dx.doi.org/10.1186/s13229-020-00338-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183643PMC
April 2020

Profiles and Predictors of Academic and Social School Functioning among Children with Autism Spectrum Disorder.

J Clin Child Adolesc Psychol 2020 Apr 23:1-13. Epub 2020 Apr 23.

Montreal Children's Hospital, McGill University.

: The purpose of the study was to identify profiles and predictors of academic and social functioning in a sample of school-age children with autism spectrum disorder.: The study included 178 children (88% boys, 75% Caucasian, ages 10-11) who completed a standardized measure of academic skills and whose teachers completed a related measure. Measures of both academic and social performance were used to construct profiles of school functioning. Measures of language, nonverbal IQ, autism symptom severity, behavior difficulties, and early social-communication skills between ages 3 and 4 were used to examine predictors of profile membership. Latent Profile Analysis was used to identify and describe profiles of children's academic and social school functioning. Profile membership was then regressed on each of the predictors using a series of multinomial logistic regression models. Finally, a multivariate model that included all significant predictors was built to examine the best fitting constellation of profile predictors.: Four profiles - reflecting variation in academic achievement, school engagement, socialization skills, pragmatic language use, and social relationships - captured the diverse school functioning outcomes of the sample. Profile membership was predicted by variation in imitation, responding to joint attention, language ability, nonverbal IQ and behavior difficulties between ages 3 and 4 years. However, in a multivariate model, only language and behavior difficulties emerged as significant predictors.: A person-centered approach to targeted early intervention that reduces behavior difficulties and enhances social-communication and language abilities may prove especially important for the promotion of later academic and social functioning at school.
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http://dx.doi.org/10.1080/15374416.2020.1750021DOI Listing
April 2020

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

J Child Psychol Psychiatry 2021 Jan 20;62(1):97-106. Epub 2020 Apr 20.

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1111/jcpp.13242DOI Listing
January 2021

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

J Child Psychol Psychiatry 2021 Jan 20;62(1):97-106. Epub 2020 Apr 20.

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1111/jcpp.13242DOI Listing
January 2021

Factor analysis of the children's sleep habits questionnaire among preschool children with autism spectrum disorder.

Res Dev Disabil 2020 Feb 2;97:103548. Epub 2020 Jan 2.

Integrated Services for Autism and Neurodevelopmental Disorders, Toronto.

Background: Sleep problems are prevalent among young children with autism spectrum disorders (ASD). The Children's Sleep Habits Questionnaire (CSHQ) is commonly used for assessment, but there are outstanding questions regarding its optimal measurement model.

Aims: To examine the factor structure of the CSHQ in preschool children with ASD, and relationships between CSHQ factors and children's emotional, cognitive, and behavioral dysregulation.

Methods And Procedures: Participants included 4- to 5-year-olds with ASD (n = 281). Confirmatory factor analysis was used to examine whether two previously reported CSHQ factor structures provided adequate fit to the sample data. Exploratory Factor Analysis (EFA) was used examine alternative models. Regression analyses were used to examine how CSHQ factor scores explained variance in dysregulation symptoms, measured by the Child Behavior Checklist.

Results: Previously reported factor models in children with ASD were not confirmed, but a novel five-factor model identified using EFA provided excellent fit to the sample data. Sleep factors were generally not correlated with autism symptoms but were associated with aggression, anxiety/depression and attention problems, with evidence of specificity in these relationships.

Conclusions: The proposed CSHQ five-factor model may be useful in future studies of sleep problems in young children with ASD.
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http://dx.doi.org/10.1016/j.ridd.2019.103548DOI Listing
February 2020

Factor analysis of the children's sleep habits questionnaire among preschool children with autism spectrum disorder.

Res Dev Disabil 2020 Feb 2;97:103548. Epub 2020 Jan 2.

Integrated Services for Autism and Neurodevelopmental Disorders, Toronto.

Background: Sleep problems are prevalent among young children with autism spectrum disorders (ASD). The Children's Sleep Habits Questionnaire (CSHQ) is commonly used for assessment, but there are outstanding questions regarding its optimal measurement model.

Aims: To examine the factor structure of the CSHQ in preschool children with ASD, and relationships between CSHQ factors and children's emotional, cognitive, and behavioral dysregulation.

Methods And Procedures: Participants included 4- to 5-year-olds with ASD (n = 281). Confirmatory factor analysis was used to examine whether two previously reported CSHQ factor structures provided adequate fit to the sample data. Exploratory Factor Analysis (EFA) was used examine alternative models. Regression analyses were used to examine how CSHQ factor scores explained variance in dysregulation symptoms, measured by the Child Behavior Checklist.

Results: Previously reported factor models in children with ASD were not confirmed, but a novel five-factor model identified using EFA provided excellent fit to the sample data. Sleep factors were generally not correlated with autism symptoms but were associated with aggression, anxiety/depression and attention problems, with evidence of specificity in these relationships.

Conclusions: The proposed CSHQ five-factor model may be useful in future studies of sleep problems in young children with ASD.
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http://dx.doi.org/10.1016/j.ridd.2019.103548DOI Listing
February 2020

A large data resource of genomic copy number variation across neurodevelopmental disorders.

NPJ Genom Med 2019 7;4:26. Epub 2019 Oct 7.

1The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON Canada.

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are , , , , , , , , , , and long non-coding RNAs: and . We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.
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http://dx.doi.org/10.1038/s41525-019-0098-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779875PMC
October 2019

Sex Differences in Social Adaptive Function in Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder.

Front Psychiatry 2019 12;10:607. Epub 2019 Sep 12.

Autism Research Centre, Bloorview Research Institute, Toronto, ON, Canada.

Social-communication difficulties, a hallmark of ASD, autism spectrum disorder (ASD) are often observed in attention - deficit/ hyperactivity disorder (ADHD), although are not part of its diagnostic criteria. Despite sex differences in the prevalence of ASD and ADHD, research examining how sex differences manifest in social and communication functions in these disorders remains limited, and findings are mixed. This study investigated potential sex differences with age in social adaptive function across these disorders, relative to controls. One hundred fifteen youth with ASD, 172 youth with ADHD, and 63 typically developing controls (age range 7-13 years, 75% males) were recruited from the Province of Ontario Neurodevelopmental Disorder (POND) Network. Social adaptive function was assessed using the Adaptive Behavior Assessment System-Second Edition (ABAS-II). The proportions of adaptive behaviors present in each skill area were analyzed as a binomial outcome using logistic regression, controlling for age, and testing for an age-by-sex interaction. In an exploratory analysis, we examined the impact of controlling for core symptom severity on the sex effect. Significant sex-by-age interactions were seen within ASD in the communication (p = 0.005), leisure (p = 0.003), and social skill areas (p < 0.0001). In all three areas, lower scores (indicating poorer function) were found in females compared to males at older ages despite females performing better at younger ages. There were significant differences in the sex-by-age interactions in the social and leisure domains between those with ASD and typically developing controls, with typically developing females showing better scores at older, compared to younger, ages. There were also significant differences in the sex-by-age interactions between ASD and ADHD on the social and leisure domains, as females with ADHD consistently scored higher on social skills than males across all ages, unlike those with ASD. Sex differences across age in the social domains for ADHD were similar to those in the typically developing group. Sex differences in social and communication skill areas were observed between ASD and ADHD, and typically developing controls, with females with ASD performing worse than males at older ages, despite an earlier advantage. These findings reinforce the need to take a developmental approach to understanding sex differences which may have diagnostic, prognostic, and treatment implications.
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http://dx.doi.org/10.3389/fpsyt.2019.00607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751776PMC
September 2019

Repetitive Behavior Severity as an Early Indicator of Risk for Elevated Anxiety Symptoms in Autism Spectrum Disorder.

J Am Acad Child Adolesc Psychiatry 2020 07 18;59(7):890-899.e3. Epub 2019 Sep 18.

University of Toronto, Ontario, Canada; Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address:

Objective: A significant proportion of children with autism spectrum disorder (ASD) will develop an anxiety disorder during childhood. Restricted and repetitive behavior severity in ASD positively correlates with anxiety severity in cross-sectional surveys. The longitudinal relationship between restricted/repetitive behavior and future anxiety symptoms is unclear.

Method: In a longitudinal cohort of children with ASD (n = 421), restricted/repetitive behavior severity at enrollment (age 2-5 years) was categorized as "mild," "moderate," or "severe" using the Autism Diagnostic Interview-Revised. Elevated anxiety symptoms were defined by a Child Behavior Checklist (parent report) Anxiety subscale T-score of >65 at ages 8 to 11 years. Multivariable logistic regression with multiple imputation for missing data was used to examine the association between restricted/repetitive behavior severity and elevated anxiety symptoms while adjusting for age, sex, adaptive functioning, baseline anxiety, income, and parenting stress, generating adjusted odds ratios (aORs) and 95% CIs.

Results: Approximately 58% of children with severe restricted/repetitive behavior at enrollment had elevated anxiety symptoms by age 11, compared to 41% of those with moderate, and 20% of those with mild restricted/repetitive behavior, respectively. Moderate and severe restricted/repetitive behavior were both associated with increased odds of elevated anxiety (moderate aOR: 2.5 [1.2-5.3]; severe aOR: 3.2 (1.4-7.5]).

Conclusion: Restricted/repetitive behavior severity at time of ASD diagnosis indicates risk for future anxiety symptoms. This finding increases our understanding of which children with ASD will develop anxiety disorders and may guide research concerning early interventions and etiological mechanisms.
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http://dx.doi.org/10.1016/j.jaac.2019.08.478DOI Listing
July 2020

Predictors of longer-term development of expressive language in two independent longitudinal cohorts of language-delayed preschoolers with Autism Spectrum Disorder.

J Child Psychol Psychiatry 2020 07 19;61(7):826-835. Epub 2019 Aug 19.

Tel Aviv University, Tel Aviv, Israel.

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.
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http://dx.doi.org/10.1111/jcpp.13117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028445PMC
July 2020

The Need for a Developmentally Based Measure of Social Communication Skills.

J Am Acad Child Adolesc Psychiatry 2019 06;58(6):555-560

Pediatrics and Developmental Neuroscience Branch, National Institute of Mental Health, Bethesda, MD.

The ability to demonstrate and quantify changes in social communication skills has been hindered by a lack of existing measures with appropriate standardization and psychometric properties. Such a measure would be helpful for research in many populations but would be particularly crucial for detecting incremental changes in youth with neurodevelopmental disorders who might gain skills but still lag substantially behind same-age peers. Although study designs and statistical methods are under development to try to account for slow and/or nonlinear, but potentially meaningful, improvements, there is a dearth of measures designed to capture growth and loss of social communication skills. This opinion piece outlines the argument for such a measure and the primary issues to consider in its development.
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http://dx.doi.org/10.1016/j.jaac.2018.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599636PMC
June 2019

Developmental Trajectories of Feeding Problems in Children with Autism Spectrum Disorder.

J Pediatr Psychol 2019 09;44(8):988-998

Child Evaluative Health Sciences, Hospital for Sick Children.

Objective: Although feeding problems are a common concern in children with autism spectrum disorder (ASD), few longitudinal studies have examined their persistence over time. The purpose of this study was to examine the developmental progression of feeding problems across four time points in preschoolers with ASD.

Methods: Group-based trajectory analyses revealed four distinct trajectories of feeding problems in our sample (N = 396).

Results: The majority of children showed levels of feeding problems that were low from the outset and stable (Group 1; 26.3%) or moderate and declining over time (Group 2; 38.9%). A third group (26.5%) showed high levels of feeding problems as preschoolers that declined to the average range by school age. Few participants (8.3%) showed evidence of severe chronic feeding problems. Feeding problems were more highly correlated with general behavior problems than with autism symptom severity.

Conclusions: Overall, our findings demonstrated that in our sample of children with ASD, most feeding problems remitted over time, but a small subgroup showed chronic feeding problems into school age. It is important to consider and assess feeding problems in ASD against the backdrop of typical development, as many children with ASD may show improvement with age.
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http://dx.doi.org/10.1093/jpepsy/jsz033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705712PMC
September 2019

Assuming ability of youth with autism: Synthesis of methods capturing the first-person perspectives of children and youth with disabilities.

Autism 2019 11 27;23(8):1882-1896. Epub 2019 Mar 27.

McGill University, Canada.

Most research regarding youth with autism spectrum disorder has not focused on their first-person perspectives providing limited insight into methodologies best suited to eliciting their voices. We conducted a synthesis of methods previously used to obtain the first-person perspectives of youth with various disabilities, which may be applicable to youth with autism spectrum disorder. Two-hundred and eighty-four articles met the inclusion criteria of our scoping review. We identified six distinct primary methods (questionnaires, interviews, group discussion, narratives, diaries, and art) expressed through four communication output modalities (language, sign language and gestures, writing, and images). A group of parents who have children with autism spectrum disorder were then presented with a synthesis of results. This parent consultation was used to build on approaches identified in the literature. Parents identified barriers that may be encountered during participant engagement and provided insights on how best to conduct first-person research with youth with autism spectrum disorder. Based on our findings, we present a novel methodological framework to capture the perspectives of youth with various communication and cognitive abilities, while highlighting family, youth, and expert contributions.
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http://dx.doi.org/10.1177/1362361319831487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779014PMC
November 2019

Developmental functioning and symptom severity influence age of diagnosis in Canadian preschool children with autism.

Paediatr Child Health 2019 Feb 2;24(1):e57-e65. Epub 2018 Jul 2.

Department of Psychiatry, McGill University, Montreal, Quebec.

Background: Early diagnosis of autism spectrum disorder (ASD) is essential in most Canadian jurisdictions to access interventions that improve long-term child outcomes. Our main objective was to identify factors associated with timing of ASD diagnosis in five provinces across Canada.

Methods: Factors influencing age of diagnosis were assessed in the analyses of an inception cohort of children diagnosed with ASD between ages 2 and 5 years. We examined bivariate associations and using a series of multiple variable regression models, evaluated the unique contributions of developmental functioning, ASD symptoms and demographic variables. Children with known genetic abnormalities, or severe sensory or motor impairments interfering with assessment were excluded.

Results: Participants were 421 children (84.6% boys). The mean age of diagnosis was 38.2 months (SD=8.7), an average of 19 months after parents identified initial concerns. Factors associated with later diagnosis included more advanced language and cognitive skills, and higher levels of restricted repetitive behaviour symptoms. Child sex and family demographics were associated with age of diagnosis. In regression analyses, language and cognitive skills accounted for 6.8% of variance in age of diagnosis and ASD symptoms contributed an additional 5.5%. Provincial site accounted for 4.0% of variance in age of diagnosis, independent of developmental skills and ASD symptoms.

Interpretation: Diagnosis of ASD occurred, on average, 19 months after parents' initial concerns. Language and cognitive skills, symptom severity and provincial site accounted for variation in age of ASD diagnosis in this Canadian cohort. Variable presentation across the developmental continuum must be considered in planning assessment services to ensure timely ASD diagnosis so that outcomes can be improved. Policy and practice leadership is also needed to reduce interprovincial variability.
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http://dx.doi.org/10.1093/pch/pxy076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376294PMC
February 2019

Structural neuroimaging correlates of social deficits are similar in autism spectrum disorder and attention-deficit/hyperactivity disorder: analysis from the POND Network.

Transl Psychiatry 2019 02 4;9(1):72. Epub 2019 Feb 4.

Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD) have been associated with difficulties recognizing and responding to social cues. Neuroimaging studies have begun to map the social brain; however, the specific neural substrates contributing to social deficits in neurodevelopmental disorders remain unclear. Three hundred and twelve children underwent structural magnetic resonance imaging of the brain (controls = 32, OCD = 44, ADHD = 77, ASD = 159; mean age = 11). Their social deficits were quantified on the Social Communication Questionnaire (SCQ) and the Reading the Mind in the Eyes Test (RMET). Multivariable regression models were used to examine the structural neuroimaging correlates of social deficits, with both a region of interest and a whole-brain vertex-wise approach. For the region of interest analysis, social brain regions were grouped into three networks: (1) lateral mentalization (e.g., temporal-parietal junction), (2) frontal cognitive (e.g., orbitofrontal cortex), and (3) subcortical affective (e.g., limbic system) regions. Overall, social communication deficits on the SCQ were associated with thinner cortices in the left lateral regions and the right insula, and decreased volume in the ventral striatum, across diagnostic groups (p = 0.006 to <0.0001). Smaller subcortical volumes were associated with more severe social deficits on the SCQ in ASD and ADHD, and less severe deficits in OCD. On the RMET, larger amygdala/hippocampal volumes were associated with fewer deficits across groups. Overall, patterns of associations were similar in ASD and ADHD, supporting a common underlying biology and the blurring of the diagnostic boundaries between these disorders.
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http://dx.doi.org/10.1038/s41398-019-0382-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361977PMC
February 2019

Gender Differences in Pragmatic Communication in School-Aged Children with Autism Spectrum Disorder (ASD).

J Autism Dev Disord 2019 May;49(5):1937-1948

Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.

Possible gender differences in manifestations of autism spectrum disorder (ASD) were examined using data on production of narratives. The Expression, Reception and Recall of Narrative Instrument (ERRNI; Bishop, Expression, Reception and Recall of Narrative Instrument, Harcourt assessment, London, 2004) was administered to a sample of matched 8-year-old intellectually able boys and girls with ASD (13M, 13F), who had been selected from a large, longitudinal study. In addition, transcripts of the narratives were analyzed in detail. Significant gender differences were found in narrative production. Girls included more salient story elements than boys. On detailed language analysis, girls were also shown to tell richer stories, including more descriptors of planning or intention. Overall, our findings suggest that subtle differences in social communication may exist between intellectually able boys and girls with ASD. If reliably identifiable in young children, such gender differences may contribute to differential diagnosis of ASD. In addition, such differences may pave the way for differential approaches to intervention when the target is effective communication in sophisticated discourse contexts.
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http://dx.doi.org/10.1007/s10803-018-03873-2DOI Listing
May 2019

Psychometric Properties of the Merrill-Palmer-Revised Scales of Development in Preschool Children With Autism Spectrum Disorder.

Assessment 2020 12 20;27(8):1796-1809. Epub 2018 Dec 20.

McMaster University, Hamilton, Ontario, Canada.

Psychometrically sound tests of intellectual ability are indispensable for research and assessment of children with autism spectrum disorder (ASD), yet few tests have been validated for use with this population. The Merrill-Palmer-Revised Scales of Development (M-P-R) is a standardized test of intellectual ability that was validated for use with typically developing preschoolers. The current study's aim was to investigate the criterion validity of the M-P-R for assessing cognitive skills in preschoolers with ASD ( = 180). Good concurrent validity was demonstrated, with a large positive correlation between the M-P-R Receptive Language domain and the PLS-4 Auditory Comprehension subscale. The Cognitive domain of the M-P-R showed a medium positive correlation with later WISC-4 scores, showing acceptable predictive validity. Cognitive strengths and weaknesses assessed using the M-P-R mirrored those described for other measures, with most children obtaining higher standard scores on the Cognitive than the Receptive Language domain. An exploratory factor analysis suggested that one factor accounted for the majority of variability in M-P-R domains.
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http://dx.doi.org/10.1177/1073191118818754DOI Listing
December 2020

Reframing Optimal Outcomes in Autism.

JAMA Pediatr 2018 08;172(8):716-717

Department of Human Development and Psychology, University of California, Los Angeles.

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http://dx.doi.org/10.1001/jamapediatrics.2018.1016DOI Listing
August 2018