Search

Abstract Background Very large sample sizes are often needed to capture heterogeneity in autism, necessitating data sharing across multiple studies with diverse assessment instruments. In these cases, data harmonization can be a critical tool for deriving a single dataset for analysis. This can be done through computational approaches that enable the conversion of scores across various instruments. To this end, our study examined the use of analytical approaches for mapping scores on two measures of adaptive functioning, namely predicting the scores on the vineland adaptive behavior scales II (VABS) from the scores on the adaptive behavior assessment system II (ABAS). Methods Data from the province of Ontario neurodevelopmental disorders network were used. The dataset included scores VABS and the ABAS for 720 participants (autism n = 547, 433 male, age: 11.31 ± 3.63 years; neurotypical n = 173, 95 male, age: 12.53 ± 4.05 years). Six regression approaches (ordinary least squares (OLS) linear regression, ridge regression, ElasticNet, LASSO, AdaBoost, random forest) were used to predict VABS total scores from the ABAS scores, demographic variables (age, sex), and phenotypic measures (diagnosis; core and co-occurring features; IQ; internalizing and externalizing symptoms). Results The VABS scores were significantly higher than the ABAS scores in the autism group, but not the neurotypical group (median difference: 8, 95% CI = (7,9)). The difference was negatively associated with age (beta = -1.2 ± 0.12, t = -10.6, p

Abstract The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist – Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, r POND-HBN = −0.97; FC feature vectors, r POND-HBN = −0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, r POND-HBN = −0.99; FC feature vectors, r POND-HBN = −0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.

Abstract Neurodevelopmental conditions can be associated with decreased health-related quality of life; however, the predictors of these outcomes remain largely unknown. We characterized the predictors of health-related quality of life (HRQoL) in a sample of neurodiverse children and youth. We used a cross-sectional subsample from the Province of Ontario Neurodevelopmental Disorders Network (POND) consisting of those children and young people in the POND dataset with complete study data (total n = 615; 31% female; age: 11.28 years ± 2.84 years). Using a structural equation model, we investigated the effects of demographics (age, sex, socioeconomic status), core features (Social Communication Questionnaire, Toronto Obsessive Compulsive Scale, Strengths and Weaknesses of attention deficit/hyperactivity disorder (ADHD)-symptoms and Normal Behavior), co-occurring symptoms (Child Behaviour Checklist), and adaptive functioning (Adaptive Behaviour Assessment System) on HRQoL (KINDL). A total of 615 participants had complete data for this study (autism = 135, ADHD = 273, subthreshold ADHD = 7, obsessive–compulsive disorder (OCD) = 38, sub-threshold OCD = 1, neurotypical = 161). Of these participants, 190 (31%) identified as female, and 425 (69%) identified as male. The mean age was 11.28 years ± 2.84 years. Health-related quality of life was negatively associated with co-occurring symptoms (B = − 0.6, SE = 0.20, CI (− 0.95, − 0.19), p = 0.004)) and age (B = − 0.1, SE = 0.04, CI (− 0.19, − 0.01), p = 0.037). Fewer co-occurring symptoms were associated with higher socioeconomic status (B = − 0.5, SE = − 0.05, CI (− 0.58, − 0.37), p

Abstract Background Previous research has demonstrated heterogeneous adaptive outcomes across the autism spectrum; however, the current literature remains limited in elucidating turning points and associated factors for longitudinal variability (chronogeneity). To address these empirical gaps, we aimed to provide a finer‐grained characterization of trajectories of adaptive functioning from early childhood to adolescence in autism. Methods Our sample (N = 406) was drawn from an inception cohort of children diagnosed Autistic at ages 2–5. Adaptive functioning was assessed with Vineland Adaptive Behavior Scales (VABS, 2nd Edition) across 6 visits from the time of diagnosis by age 18. Parallel‐process latent growth curve modeling were used to estimate domain‐level VABS trajectories, followed by latent class growth analysis to identify trajectory subgroups. Child characteristics at diagnosis, family demographics, and participation outcomes at adolescence were compared across subgroups. Results Piecewise latent growth models best described VABS trajectories with two turning points identified at around ages 5‐6 and 9–10, respectively reflecting transitions into school age and early adolescence. We parsed four VABS trajectory subgroups that vary by level of functioning and change rate for certain domains and periods. Around 16% of the sample exhibited overall adequate functioning (standard score >85) with notable early growth and social adaptation during adolescence. About 21% showed low adaptive functioning (standard score ≤70), with decreasing slopes by age 6 followed by improvements in communication and daily‐living skills by age 10. The other two subgroups (63% in total) were characterized by adaptive functioning between low and adequate levels, with relatively stable trajectories entering school age. These subgroups differed most in their cognitive ability at diagnosis, household income, and social participation in adolescence. Conclusions We identified key individual and family characteristics and time windows associated with distinct adaptive functioning trajectories, which have important implications for providing timely and tailored supports to Autistic people across developmental stages.

IntroductionThis study examined the prevalence of functional difficulties and associated factors in Canadian children/youth aged 5 to 17 years diagnosed with autism spectrum disorder (ASD). MethodsWe analyzed data from the 2019 Canadian Health Survey on Children and Youth (CHSCY), a nationally representative survey of Canadian children/youth that used the Washington Group Short Set on Functioning (WG-SS) to evaluate functioning in six daily tasks. For each functional domain, binary outcomes were derived (no/some difficulty, a lot of difficulty/no ability). We used logistic regression to identify associations between demographic characteristics, educational experiences, and perceived mental and general health and the most common functional difficulties, namely those related to remembering/concentrating, communication and self-care. All estimates were weighted to be representative of the target population. The bootstrap method was used to calculate variance estimates. ResultsAnalysis of the records of 660 children/youth with ASD revealed that the most common functional difficulties were remembering/concentrating (22%; 95% CI: 18–27), communicating (19%; 95% CI: 15–23) and self-care (13%; 95% CI: 10–17). Lower perceived mental health was associated with increased functional difficulties with remembering/concentrating. ASD diagnosis at a lower age and lower perceived general health were associated with increased functional difficulty with communication. Parental expectations for postsecondary education were associated with decreased functional difficulty for self-care. ConclusionOne or more functional difficulties from the WG-SS was present in 39% of Canadian children/youth aged 5 to 17 years with ASD. Functional difficulties with remembering/concentrating, communication and self-care were most common.

IntroductionCette étude porte sur la prévalence des difficultés fonctionnelles et des facteurs connexes chez les enfants et les jeunes canadiens de 5 à 17 ans ayant reçu un diagnostic de trouble du spectre de l'autisme (TSA). MéthodologieNous avons analysé les données tirées de l’Enquête canadienne sur la santé des enfants et des jeunes (ECSEJ) de 2019, une enquête nationale représentative de la population canadienne d’enfants et de jeunes, qui utilisait l’ensemble abrégé de questions sur le fonctionnement du Groupe de Washington (Washington Group Short Set on Functioning, WG-SS) pour évaluer le fonctionnement dans le cadre de six tâches quotidiennes. Pour chaque domaine fonctionnel, des résultats binaires ont été générés (aucune difficulté/quelques difficultés, beaucoup de difficultés/n’y parvient pas du tout). Nous avons ensuite utilisé une régression logistique pour déterminer les associations entre, d’une part, les caractéristiques sociodémographiques, les expériences d’apprentissage et la santé générale et mentale perçue et, d’autre part, les difficultés fonctionnelles les plus courantes, celles liées à la mémoire/concentration, à la communication et aux soins personnels. Toutes les estimations ont été pondérées de façon à être représentatives de la population cible. Nous avons utilisé la méthode « bootstrap » pour établir les estimations de la variance. RésultatsL’analyse des données des 660 enfants et jeunes atteints d’un TSA a révélé que les difficultés fonctionnelles les plus courantes concernaient la mémoire/concentration (22 %; IC à 95 % : 18 à 27), la communication (19 %; IC à 95 % : 15 à 23) et les soins personnels (13 %; IC à 95 % : 10 à 17). Une moins bonne santé mentale perçue était associée à des difficultés fonctionnelles accrues liées à la mémoire/concentration. Un diagnostic de TSA à un plus jeune âge et une moins bonne santé générale perçue étaient associés à des difficultés fonctionnelles accrues liées à la communication. Le fait que les parents avaient des attentes en matière d’études postsecondaires était associé à des difficultés fonctionnelles réduites liées aux de soins personnels. ConclusionL’étude a révélé que 39 % des enfants et des jeunes canadiens de 5 à 17 ans ayant reçu un diagnostic de TSA présentaient au moins une difficulté fonctionnelle citée dans l’ensemble de questions WG-SS, les difficultés fonctionnelles liées à la mémoire/ concentration, à la communication et aux soins personnels étant les plus fréquentes.

There is an increasing desire to study neurodevelopmental disorders (NDDs) together to understand commonalities to develop generic health promotion strategies and improve clinical treatment. Common data elements (CDEs) collected across studies involving children with NDDs afford an opportunity to answer clinically meaningful questions. We undertook a retrospective, secondary analysis of data pertaining to sleep in children with different NDDs collected through various research studies. The objective of this paper is to share lessons learned for data management, collation, and harmonization from a sleep study in children within and across NDDs from large, collaborative research networks in the Ontario Brain Institute (OBI). Three collaborative research networks contributed demographic data and data pertaining to sleep, internalizing symptoms, health-related quality of life, and severity of disorder for children with six different NDDs: autism spectrum disorder; attention deficit/hyperactivity disorder; obsessive compulsive disorder; intellectual disability; cerebral palsy; and epilepsy. Procedures for data harmonization, derivations, and merging were shared and examples pertaining to severity of disorder and sleep disturbances were described in detail. Important lessons emerged from data harmonizing procedures: prioritizing the collection of CDEs to ensure data completeness; ensuring unprocessed data are uploaded for harmonization in order to facilitate timely analytic procedures; the value of maintaining variable naming that is consistent with data dictionaries at time of project validation; and the value of regular meetings with the research networks to discuss and overcome challenges with data harmonization. Buy-in from all research networks involved at study inception and oversight from a centralized infrastructure (OBI) identified the importance of collaboration to collect CDEs and facilitate data harmonization to improve outcomes for children with NDDs.

Introduction The developmentally variable nature of autism poses challenges in providing timely services tailored to a child’s needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child’s day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (

IntroductionPrevalence rates of emotional and behavior problems (EBP) in autistic children and youth are high (40–70%), and often cause severe and chronic impairment. Furthermore, autistic children are also more likely to experience family “social-ecological” adversity compared to neurotypically developing peers, including social isolation, child maltreatment, caregiver mental illness, and socioeconomic risk. These family stressors increase the risk of co-occurring EBP among autistic children and can often impede access to evidence-based care, thus amplifying long-term health inequities for autistic children and their caregivers. In the current autism services landscape, there are few scalable, evidence-based programs that adequately address these needs. The Family Check-Up (FCU®) is a brief, strength-based, and tailored family-centered intervention that supports positive parenting and explicitly assesses the social determinants of child and family mental health within an ecological framework. Studies have demonstrated long-term positive child and caregiver outcomes in other populations, but the FCU® has not been evaluated in families of autistic children and youth. Therefore, we aimed to evaluate FCU® implementation within an established, publicly funded Autism Program in Ontario, Canada, with delivery by autism therapists, to demonstrate sustainable effectiveness within real-world settings.MethodsIn this study, we outline the protocol for a hybrid implementation-effectiveness approach with two key components: (1) A parallel-arm randomized controlled trial of N = 80 autistic children/youth (ages 6–17 years) and high levels of EBP and their caregivers. Primary and secondary outcomes include child EBP, and caregiver well-being and parenting. (2) A mixed methods implementation study, to describe facilitators and barriers to implementation of the FCU® within an autism service setting.DiscussionScalable, ecologically focused family-centered interventions offer promise as key components of a public health framework aimed at reducing mental health inequities among autistic children, youth, and their caregivers. Results of this study will inform further program refinement and scale-up.

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

Background Parent and child mental health has suffered during the pandemic and transition phase. Structured and shared parenting may be intervention targets beneficial to families who are struggling with parent or child mental health challenges. Aims First, we investigated associations between structured and shared parenting and parent depression symptoms. Second, we investigated associations between structured and shared parenting and depression, hyperactivity/inattention and irritability symptoms in children. Method A total of 1027 parents in two-parent households (4797 observations total; 85.1% mothers) completed online surveys about themselves and their children (aged 2–18 years) from April 2020 to July 2022. Structured parenting and shared parenting responsibilities were assessed from April 2020 to November 2021. Symptoms of parent depression, child depression, child hyperactivity and inattention, child irritability, and child emotional and conduct problems were assessed repeatedly (one to 14 times; median of four times) from April 2020 to July 2022. Results Parents who reported higher levels of shared parenting responsibilities had lower depression symptoms (β = −0.09 to −0.32, all P < 0.01) longitudinally. Parents who reported higher levels of shared parenting responsibilities had children with fewer emotional problems (ages 2–5 years; β = −0.07, P < 0.05), fewer conduct problems (ages 2–5 years; β = −0.09, P < 0.01) and less irritability (ages 13–18 years; β = −0.27, P < 0.001) longitudinally. Structured parenting was associated with fewer conduct problems (ages 2–5 years; β = −0.05, P < 0.05). Conclusions Shared parenting is beneficial for parent and child mental health, even under chaotic or inflexible life conditions. Structured parenting is beneficial for younger children.

ObjectiveThe objectives of this study were to determine rates of sleep disturbances in children with neurodevelopmental disorders (NDDs) within and across disorders and compared to typically developing (TD) children and to describe differences above and below the clinical cut-off for sleep disturbances. In addition, we explored the associations between demographic variables, severity of disorder, sleep disturbances, internalizing symptoms, and health-related quality of life (HRQOL) in children with NDDs.MethodWe conducted cross-sectional data analyses of an existing database with community-dwelling children with NDDs (n = 1438) and TD children (n = 140) aged 4–12 years. Parent-reported measures on sleep disturbances using the Children's Sleep Habits Questionnaire (CSHQ), internalizing symptoms using the Revised Children's Anxiety and Depression Scale, and HRQOL using the KINDL-R were assessed. Hierarchical linear regression examined the associations between demographic variables, severity of disorder, sleep disturbances, internalizing symptoms, and HRQOL in children with NDDs.ResultsChildren with NDDs (8.5 ± 2.1 years, 69.9% M) had significantly greater total sleep disturbance index (TSDI) than TD children [(8.6 ± 2.3 years, 60.0% M) (mean difference = 6.88 [95% CI 5.37, 8.40]; p < 0.001) (n = 838 NDDs (58.3%); n = 120 TD (86.7%)]. Children with severe NDDs reported significantly greater TSDI above the clinical cut-off (i.e., ≥41; CSHQ) than those with less severe NDDs (p < 0.001). Internalizing symptoms (β = −0.082 [95% CI −0.144, −0.019]; p = 0.011) and TSDI (β = −0.226 [95% CI −0.380, −0.073]; p = 0.004) were significantly associated with HRQOL in children with NDDs.ConclusionSurveillance and management of sleep and internalizing symptoms are needed to improve HRQOL in children with NDDs. Commonalities in sleep disturbances for children with NDDs support transdiagnostic interventions to treat sleep.

Introduction: Poor quality T1-weighted brain scans systematically affect the calculation of brain measures. Removing the influence of such scans requires identifying and excluding scans with noise and artefacts through a quality control (QC) procedure. While QC is critical for brain imaging analyses, it is not yet clear whether different QC approaches lead to the exclusion of the same participants. Further, the removal of poor-quality scans may unintentionally introduce a sampling bias by excluding the subset of participants who are younger and/or feature greater clinical impairment. This study had two aims: (1) examine whether different QC approaches applied to T1-weighted scans would exclude the same participants, and (2) examine how exclusion of poor-quality scans impacts specific demographic, clinical and brain measure characteristics between excluded and included participants in three large pediatric neuroimaging samples. Methods: We used T1-weighted, resting-state fMRI, demographic and clinical data from the Province of Ontario Neurodevelopmental Disorders network (Aim 1: n = 553, Aim 2: n = 465), the Healthy Brain Network (Aim 1: n = 1051, Aim 2: n = 558), and the Philadelphia Neurodevelopmental Cohort (Aim 1: n = 1087; Aim 2: n = 619). Four different QC approaches were applied to T1-weighted MRI (visual QC, metric QC, automated QC, fMRI-derived QC). We used tetrachoric correlation and inter-rater reliability analyses to examine whether different QC approaches excluded the same participants. We examined differences in age, mental health symptoms, everyday/adaptive functioning, IQ and structural MRI-derived brain indices between participants that were included versus excluded following each QC approach. Results: Dataset-specific findings revealed mixed results with respect to overlap of QC exclusion. However, in POND and HBN, we found a moderate level of overlap between visual and automated QC approaches (rtet=0.52–0.59). Implementation of QC excluded younger participants, and tended to exclude those with lower IQ, and lower everyday/adaptive functioning scores across several approaches in a dataset-specific manner. Across nearly all datasets and QC approaches examined, excluded participants had lower estimates of cortical thickness and subcortical volume, but this effect did not differ by QC approach. Conclusion: The results of this study provide insight into the influence of QC decisions on structural pediatric imaging analyses. While different QC approaches exclude different subsets of participants, the variation of influence of different QC approaches on clinical and brain metrics is minimal in large datasets. Overall, implementation of QC tends to exclude participants who are younger, and those who have more cognitive and functional impairment. Given that automated QC is standardized and can reduce between-study differences, the results of this study support the potential to use automated QC for large pediatric neuroimaging datasets.

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing prevalence worldwide. Early identification of ASD through developmental screening is critical for early intervention and improved behavioural outcomes in children. However due to long wait times, delays in diagnosis continue to occur, particularly among minority populations who are faced with existing barriers in access to care. A novel Mobile Developmental Outreach Clinic (M-DOC) was implemented to deliver culturally sensitive screening and assessment practices to increase access to developmental health services, reduce wait times in diagnoses, and aid in equitable access to intervention programs among vulnerable populations in Ontario. Methods This study applied two evaluation frameworks (process and outcome evaluation) to determine whether the delivery model was implemented as intended, and if the program achieved its targeted goals. A mixed-methods design was undertaken to address the study objectives. Results Between September 2018–February 2020, M-DOC reached 227 families with developmental health concerns for their child, while successfully targeting the intended population and achieving its goals. The mean age of the child-in-need at intake was 31.6 months (SD 9.9), and 70% of the sample were male. The program’s success was attributed to the use of cultural liaisons to break cultural and linguistic barriers, the creation of multiple points of access into the diagnosis pathway, and delivery of educational workshops in local communities to raise awareness and knowledge of autism spectrum disorder. Conclusions The findings underscore the need for community-based intervention programs that focus on cultural barriers to accessing health services. The model of delivery of the M-DOC programs highlights the opportunity for other programs to adopt a similar mobile outreach clinic approach as a means to increase access to services, particularly in targeting hard-to-reach and vulnerable populations.

Abstract Autism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome sequence data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 18 individuals from 16 unrelated families carrying a heterozygous guanine duplication (c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (genomic location [hg38]g.50,721,512dup) affecting SHANK3, a prototypical ASD gene (0.08% of ASD-affected individuals carried the predicted p.Ala1227Glyfs*69 frameshift variant). Most probands carried de novo mutations, but five individuals in three families inherited it through somatic mosaicism. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (17/17) formally tested for ASD carried a diagnosis, there was the variable expression of core ASD features both within and between families. Defining such recurrent mutational mechanisms underlying an ASD outcome is important for genetic counseling and early intervention.

Abstract Background Atypical reactions to the sensory environment are often reported in autistic individuals, with a high degree of variability across the sensory modalities. These sensory differences have been shown to promote challenging behaviours and distress in autistic individuals and are predictive of other functions including motor, social, and cognitive abilities. Preliminary research suggests that specific sensory differences may cluster together within individuals creating discrete sensory phenotypes. However, the manner in which these sensory differences cluster, and whether the resulting phenotypes are associated with specific cognitive and social challenges is unclear. Methods Short sensory profile data from 599 autistic children and adults between the ages of 1 and 21 years were subjected to a K-means cluster analysis. Analysis of variances compared age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder across the resultant clusters. Results A five-cluster model was found to minimize error variance and produce five sensory phenotypes: (1) sensory adaptive, (2) generalized sensory differences, (3) taste and smell sensitivity, (4) under-responsive and sensation seeking, and (5) movement difficulties with low energy. Age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder were found to differ significantly across the five phenotypes. Limitations The results were based on parent-report measures of sensory processing, adaptive behaviour, traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder, which may limit the generalizability of the findings. Further, not all measures are standardized, or psychometrically validated with an autism population. Autistic individuals with an intellectual disability were underrepresented in this sample. Further, as these data were obtained from established records from a large provincial database, not all measures were completed for all individuals. Conclusions These findings suggest that sensory difficulties in autistic individuals can be clustered into sensory phenotypes, and that these phenotypes are associated with behavioural differences. Given the large degree of heterogeneity in sensory difficulties seen in the autistic population, these sensory phenotypes represent an effective way to parse that heterogeneity and create phenotypes that may aid in the development of effective treatments and interventions for sensory difficulties.

Objective To determine the association between pubertal stage, sex and behavioural profile across and within neurodevelopmental disorders (NDDs) compared with typically developing (TD) youth.Methods This was a cross-sectional study from the Province of Ontario Neurodevelopmental Disorders network, including children/youth with various NDDs and TD controls. Caregivers completed the Child Behavior Checklist (CBCL). Participants were grouped into three puberty stages: prepuberty (Tanner stage 1), early puberty (Tanner stages 2–3) and late puberty (Tanner stages 4–5). The association between pubertal stage and CBCL scores was assessed controlling for sex and diagnosis.Results The analysis included 1043 participants (male=733; 70.3%). A three-way interaction between pubertal status, sex and diagnosis was not significant for internalising or externalising behaviour. Diagnosis was significantly associated with CBCL scores for both internalising (p

In Ontario, Canada, school extracurricular activities and sports were modified or canceled for a prolonged period due to public health restrictions resulting from the COVID-19 pandemic. The present study aims to examine the association of changes to extracurricular and sport participation and child and youth mental health. Data were collected on child and youth mental health symptoms (n = 908) and participation in extracurricular activities and sports in the 2019–2020 and 2020–2021 academic years. Results indicated that pre-COVID (2019–2020) participation in either extracurricular activities or sports was associated with reduced anxiety, inattention, and hyperactivity during the pandemic (β range −0.08 to −0.11, p < 0.05). Participation in either extracurricular activities or sports during-COVID (2020–2021) was associated with lower depressive symptoms (β range −0.09 to −0.10, p < 0.05). Findings suggest that participation in extracurricular activities and/or school sports both before or during the COVID-19 pandemic were associated with better mental health outcomes in children and youth. Implications of this work consider future situations where restrictions on extracurricular and sport participation are reinstated and the impact of child and youth mental health.

Increasing numbers of children with known genetic conditions and/or intellectual disability are referred for evaluation of autism spectrum disorder (ASD), highlighting the need to refine autism symptom measures to facilitate differential diagnoses in children with cognitive and language impairments. Previous studies have reported decreased specificity of ASD screening and diagnostic measures in children with intellectual disability. However, little is known about how cognitive and language abilities impact the measurement of specific ASD symptoms in this group. We aggregated a large sample of young children (N = 1196; aged 31–119 months) to examine measurement invariance of ASD symptoms among minimally verbal children within the context of the Autism Diagnostic Observation Schedule (ADOS) Module 1. Using confirmatory factor analysis (CFA) and moderated non-linear factor analysis (MNLFA), we examined how discrete behaviors were differentially associated with the latent symptom domains of social communication impairments (SCI) and restricted and repetitive behaviors (RRB) across spoken language levels and non-verbal mental age groupings. While the two-factor structure of SCI and RRB held consistently across language and cognitive levels, only partial invariance was observed for both ASD symptom domains of SCI and RRB. Specifically, four out of the 15 SCI items and one out of the three RRB items examined showed differential item functioning between children with “Few to No Words” and those with “Some Words”; and one SCI item and one RRB item showed differential item functioning across non-verbal mental age groups. Moreover, even after adjusting for the differential item functioning to reduce measurement bias across groups, there were still differences in ASD symptom domain scores across spoken language levels. These findings further underscore the influence of spoken language level on measurement of ASD symptoms and the importance of measuring ASD symptoms within refined spoken language levels, even among those with minimal verbal abilities.

Abstract 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.

Impairments in emotional face processing are demonstrated by individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which is associated with altered emotion processing networks. Despite accumulating evidence of high rates of diagnostic overlap and shared symptoms between ASD and ADHD, functional connectivity underpinning emotion processing across these two neurodevelopmental disorders, compared to typical developing peers, has rarely been examined. The current study used magnetoencephalography to investigate whole-brain functional connectivity during the presentation of happy and angry faces in 258 children (5–19 years), including ASD, ADHD and typically developing (TD) groups to determine possible differences in emotion processing. Data-driven clustering was also applied to determine whether the patterns of connectivity differed among diagnostic groups. We found reduced functional connectivity in the beta band in ASD compared to TD, and a further reduction in the ADHD group compared to the ASD and the TD groups, across emotions. A group-by-emotion interaction in the gamma frequency band was also observed. Greater connectivity to happy compared to angry faces was found in the ADHD and TD groups, while the opposite pattern was seen in ASD. Data-driven subgrouping identified two distinct subgroups: NDD-dominant and TD-dominant; these subgroups demonstrated emotion- and frequency-specific differences in connectivity. Atypicalities in specific brain networks were strongly correlated with the severity of diagnosis-specific symptoms. Functional connectivity strength in the beta network was negatively correlated with difficulties in attention; in the gamma network, functional connectivity strength to happy faces was positively correlated with adaptive behavioural functioning, but in contrast, negatively correlated to angry faces. Our findings establish atypical frequency- and emotion-specific patterns of functional connectivity between NDD and TD children. Data-driven clustering further highlights a high degree of comorbidity and symptom overlap between the ASD and ADHD children.

Recent advances in longitudinal methodologies for observational studies have contributed to a better understanding of Autism as a neurodevelopmental condition characterized by within-person and between-person variability over time across behavioral domains. However, this finer-grained approach to the study of developmental variability has yet to be applied to Autism intervention science. The widely adopted experimental designs in the field—randomized control trials and quasi-experimental designs—hold value for inferring treatment effects; at the same time, they are limited in elucidating what works for whom, why, and when, given the idiosyncrasies of neurodevelopmental disorders where predictors and outcomes are often dynamic in nature. This perspective paper aims to serve as a primer for Autism intervention scientists to rethink the way we approach predictors of treatment response and treatment-related change using a dynamic lens. We discuss several empirical gaps, and potential methodological challenges and opportunities pertaining to: (1) capturing finer-grained treatment effects in specific behavioral domains as indexed by micro-level within-person changes during and beyond intervention; and (2) examining and modeling dynamic prediction of treatment response. Addressing these issues can contribute to enhanced study designs and methodologies that generate evidence to inform the development of more personalized interventions and stepped care approaches for individuals on the heterogeneous spectrum of Autism with changing needs across development.

Background: Many phenotypic studies have estimated the degree of comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), but few have examined the latent, or unobserved, structure of combined ASD and ADHD symptoms. This is an important perquisite toward better understanding the overlap between ASD and ADHD.Methods: We conducted a scoping review of studies that examined the factor or latent class structure of ASD and ADHD symptoms within the same clinical or general population sample.Results: Eight studies met final inclusion criteria. Four factor analysis studies found that ASD and ADHD domains loaded separately and one found that some ASD and ADHD domains loaded together. In the three latent class studies, there were evidence of profiles with high levels of co-occurring ASD and ADHD symptoms.Conclusions: Our scoping review provides some evidence of phenotypic overlap between ASD and ADHD at the latent, or unobserved, level, particularly when using a “person-centered” (latent class analysis) vs. a “variable-centered” (factor analysis) approach.

Abstract Background There is a need to develop a multipurpose obsessive–compulsive disorder (OCD) measure that is useful for cross disorder research and as a reliable clinical rating scale. The current study examined the psychometric properties and established clinical cutoffs for the parent‐report version of the Toronto Obsessive–Compulsive Scale (TOCS), a 21‐item rating scale of obsessive–compulsive traits. Method Participants ranged in age from 6 to 21 years old and had a primary diagnosis of OCD (n = 350, 50% female), attention‐deficit/hyperactivity disorder (ADHD) (n = 820, 25% female), autism spectrum disorder (ASD) (n = 794, 22% female), or were typically developing controls (n = 391, 51% female). Confirmatory factor analyses, internal consistency reliability, and convergent and divergent validity of the TOCS were examined in the OCD group. Using various scoring approaches, receiver operating characteristic (ROC) analyses were used to establish a clinical cut‐off by splitting the OCD group into a discovery sample (166 OCD cases, 164 controls) and a validation sample (184 OCD cases, 227 controls). Classification accuracy and TOCS scores were compared across OCD, ADHD, and ASD groups. Results The psychometric properties of the TOCS were confirmed. ROC analyses across TOCS scoring approaches in the discovery sample indicated excellent diagnostic discrimination (AUC ≥0.95, sensitivity 77%–92%, specificity 92%–98%). Established cutoffs, when applied in the independent validation sample of OCD cases and controls, showed an overall classification accuracy of 85%–90%. The TOCS total score and symptom count showed good discrimination of OCD from ADHD (AUC ≥0.86) and ASD (AUC ≥0.81). The OCD group scored significantly higher on all TOCS dimensions (except Hoarding) than the ADHD and ASD groups. Conclusion The TOCS is a reliable and valid rating scale with strong sensitivity and specificity in discriminating OCD cases from controls, as well as from ASD and ADHD. It is a quantitative OCD measure with important clinical and research applications, with particular relevance for cross disorder phenotyping and population‐based studies.

Objective: The day-to-day experience of families with an Autistic child may be shaped by both, child characteristics and available resources, which often are influenced by the socioeconomic context of the family. Using a socioecological approach, this study explored the quantitative associations between child autistic symptoms, family socioeconomic status, and family life.Methods: Data came from the Pediatric Autism Research Cohort—PARC Study (pilot). Parents of children with a recent diagnosis of autism completed a set of assessments, including the Autism Family Experience Questionnaire, Autism Impact Measure, and a Sociodemographic Questionnaire. A series of multiple, iterative linear regression models were constructed to ascertain quantitative associations between child autistic symptoms, socioeconomic context, and family life.Results: A total of 50 children (mean age: 76 months; SD: 9.5 months; and 84% male) with data on the variables of interest were included in the analysis. The frequency of child autistic symptoms was associated with family life outcomes (p = 0.02 and R2 = 24%). Once autistic symptom frequency, symptom impact, and sociodemographic variables were considered, parents of higher educational attainment reported worse family life outcomes compared to their lesser-educated counterparts. This cumulative regression model had considerable explanatory capability (p = 0.01, R2 = 40%).Conclusion: This study demonstrates the utility of using a socioecological approach to examine the dynamic interplay between child characteristics and family circumstances. Our findings suggest that family life for parents (of an autistic child) who have obtained higher education is reported (by the parents themselves) as less satisfactory compared to that of parents without higher education, once adjusted for the autistic symptom frequency of child, symptom impact, and income. These findings can inform the design and delivery of more family-centered care pathways during the years following a diagnosis of autism.

Introduction Longitudinal trajectory methods, featuring outcome assessments at three or more time points, are increasingly being used as appropriate approaches to understand developmental pathways of people on the autism spectrum across the lifespan. Understanding the scope of this rapidly expanding body of research can help inform future trajectory studies and identify areas for potential meta-analysis as well as key evidence gaps. We present the protocol for a scoping review whose objective is to identify and summarise the scope of research that uses a longitudinal trajectory study design to examine development in children diagnosed with autism. Specifically, we will identify outcome domains and age intervals that have been well characterised, areas where further research is needed and the historical use of various longitudinal trajectory analytical approaches.Methods and analysis We outline the methods for the proposed scoping review according to the framework outlined by Arksey and O’Malley, with subsequent clarifications and enhancements by other authors. Using a search strategy developed by a medical librarian, we will search six databases for relevant publications. Titles and abstracts will be screened in duplicate, followed by full-text screening. Data extraction fields developed predominantly a priori from a set of guiding subquestions will be used to chart relevant data. The findings will include quantitative aggregate summaries, narrative summaries, and appraisal of trajectory studies according to our methodological subquestions. We will consult autistic self-advocate and parent–caregiver stakeholders to facilitate interpretation of the findings.Ethics and dissemination Research ethics approval is not required for this scoping review. The results will be presented to researcher, care professional, policy-maker and stakeholder audiences at local and international conferences, other dissemination activities and published in a peer-reviewed journal.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that often involves impaired cognition, communication difficulties and restrictive, repetitive behaviors. ASD is extremely heterogeneous both clinically and etiologically, which represents one of the greatest challenges in studying the molecular underpinnings of ASD. While hundreds of ASD-associated genes have been identified that confer varying degrees of risk, no single gene variant accounts for >1% of ASD cases. Notably, a large number of ASD-risk genes function as epigenetic regulators, indicating potential epigenetic dysregulation in ASD. As such, we compared genome-wide DNA methylation (DNAm) in the blood of children with ASD (n = 265) to samples from age- and sex-matched, neurotypical controls (n = 122) using the Illumina Infinium HumanMethylation450 arrays.Results: While DNAm patterns did not distinctly separate ASD cases from controls, our analysis identified an epigenetically unique subset of ASD cases (n = 32); these individuals exhibited significant differential methylation from both controls than the remaining ASD cases. The CpG sites at which this subset was differentially methylated mapped to known ASD risk genes that encode proteins of the nervous and immune systems. Moreover, the observed DNAm differences were attributable to altered blood cell composition, i.e., lower granulocyte proportion and granulocyte-to-lymphocyte ratio in the ASD subset, as compared to the remaining ASD cases and controls. This ASD subset did not differ from the rest of the ASD cases in the frequency or type of high-risk genomic variants.Conclusion: Within our ASD cohort, we identified a subset of individuals that exhibit differential methylation from both controls and the remaining ASD group tightly associated with shifts in immune cell type proportions. This is an important feature that should be assessed in all epigenetic studies of blood cells in ASD. This finding also builds on past reports of changes in the immune systems of children with ASD, supporting the potential role of altered immunological mechanisms in the complex pathophysiology of ASD. The discovery of significant molecular and immunological features in subgroups of individuals with ASD may allow clinicians to better stratify patients, facilitating personalized interventions and improved outcomes.

Mental illness among medical students in particular, and higher education students in general, is very high. Many measures have been suggested in order to improve the situation, including training members of faculty and staff. However, to the best of our knowledge there seem to be no studies proposing training programmes for medical schools’ faculty and staff in response to recognising students’ psychological difficulties and symptoms in order to provide the relevant support. Also, in cases where such training for supporting medical students with psychological symptomatology exist, the efficacy of the approach employed is not known. By employing a careful literature search according to published guidelines for narrative literature reviews, this study aimed to fill in this identified gap in the literature. From the literature search, 14 articles were included in this review and the results show that no training tailored for faculty and staff in medical schools was identified. However, articles that related to higher education were included because they were useful in providing insights for medicine, and show the following: (a) faculty and staff acknowledged the importance of mental illness among students, (b) many of them discussed with their students psychological symptoms and provided support, (c) they tended to feel unprepared for recognising students’ psychological symptoms successfully and providing support, (d) they embraced the idea of being trained, and (e) any training seemed to be helpful for members of faculty and staff. From the results of this narrative review, we propose the CReATE circular pathway to ensure a sustainable process of training and support for students’ development.

Background: 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.Method: 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.Results: 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.Conclusion: 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.

Researchers increasingly employ longitudinal trajectory methods to understand developmental pathways of people on the autism spectrum across the lifespan. By assessing developmental or health-related outcome domains at three or more timepoints, trajectory studies can characterize their shape and varying rates of change over time. The purpose of this scoping review was to identify and summarize the published breadth of research that uses a trajectory study design to examine development in children (to age 18 years) diagnosed with autism. Using a systematic search and screening procedure, 103 studies were included. This review summarizes methodological characteristics across studies including the varying statistical approaches used. A series of figures maps where published research is available across 10 outcome domains and the ages over which children have been followed. Evidence gaps, informed by the perspectives of the autistic and caregiver stakeholders that were engaged in this review, are discussed. We recommend that future trajectory research addresses the absence of studies from low- and middle-income countries, considers longitudinal assessment of outcome domains that caregivers and autistic people consider meaningful, and plans follow-up periods with assessment timepoints that cover the gaps in ages where more outcome-specific data are needed.

Sensory processing abilities are highly variable within and across people diagnosed with autism and attention-deficit/hyperactivity disorder (ADHD). This study examined the transdiagnostic nature of sensory processing abilities, and their association with features of autism and ADHD, in a large sample of autistic people (n = 495) and people with ADHD (n = 461). Five similar data-driven sensory phenotypes characterized sensory processing abilities, and showed similar patterns of association with features of autism and ADHD, across both diagnostic groups. These results demonstrate the transdiagnostic nature of sensory processing abilities, while contributing to a growing body of literature that suggests the autism and ADHD diagnostic labels have poor explanatory power.

This study examined educators' descriptions of the positive character traits of students with autism spectrum disorder at ages 7-8 and 10-11, using an adapted version of the Values in Action (VIA) Classification of Strengths. The most commonly endorsed strengths at both age intervals were kindness, specific skills, self-regulation, and perseverance. Higher scores for challenging behavior were associated with a lower likelihood of endorsement for Happiness and Courage traits. Higher autism symptom severity scores were associated with a lower likelihood of endorsement for Courage traits. Few significant differences were found for endorsement of trait categories by students' educational placement or the type of curriculum they received. Results may have implications for student-teacher relationships, educational assessments, and school-based interventions that emphasize strengths and resilience.