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Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Research regarding autistic children's sibling relationship quality is mixed, although some literature suggests poorer quality compared to children with other disabilities or who are neurotypical. Little is known about how the clinical characteristics of autistic children relate to parent perceptions of sibling relationship quality. We drew data from a subsample of 119 children on the autism spectrum, ages 10-11 years, from an ongoing longitudinal study. Hierarchical multiple regressions tested the extent to which children's autism symptoms, behavioral difficulties, and communication abilities related to four domains of parent-rated sibling relationship quality. We also examined communication ability as a moderator of the effect of behavioral difficulties on parent-rated sibling relationship quality. More severe autism symptoms were associated with lower levels of conflict and rivalry, whereas higher communication ability was related to more relative status/power, but also conflict. Communication ability moderated the effect of behavioral difficulties such that behavioral difficulties were more closely associated with less warmth/closeness when children had weaker communication skills; behavioral difficulties were not significantly associated with other domains of sibling relationship quality. Findings underscore the importance of considering clinical characteristics and multiple domains of relationship quality to better understand how parents view the relationships between autistic children and their siblings.

We examined the narrative abilities of bilingual and monolingual children on the autism spectrum (AS), whether bilinguals presented stronger social and pragmatic language abilities compared to monolinguals, and the link between narrative, social, and pragmatic language abilities. The narrative, social, and pragmatic language skills of school-aged bilinguals (n = 54) and monolinguals (n = 80) on the AS were assessed using normed measures. Language exposure was estimated through a parent questionnaire. Bilinguals performed similarly to monolinguals on measures of narrative, social, and pragmatic language skills. However, balanced bilinguals performed better on a nonliteral language task. Overall, results indicate that bilingual children on the AS can become as proficient in using language as monolinguals and may enjoy a bilingual advantage.

Participation in daily activities is often linked to functional independence and well-being, yet individual variability in participation and factors associated with that variation have rarely been examined among autistic youth. We applied latent profile analysis to identify subgroups of youth based on parent-reported activity participation frequency at home, school and community, as well as associations with youth characteristics, family demographics and environmental supportiveness among 158 autistic youth (aged 11-14 years at baseline). Three-, three- and two-profile solutions were selected for home, school and community settings, respectively; the most prevalent profiles were characterized by frequent home participation (73%), low participation in non-classroom activities at school (65%) and low community participation, particularly in social gatherings (80%), indicating participation imbalance across settings. More active participation profiles were generally associated with greater environmental support, higher cognitive and adaptive functioning and less externalizing behaviour. Latent transition analysis revealed overall 75% stability in profile membership over approximately 1 year, with a different home participation profile emerging at the second time-point. Our findings highlighted the variable participation patterns among autistic youth as associated with individual, family and environmental factors, thus stressing the need for optimizing person-environment fit through tailored supports to promote autistic youth's participation across settings.

Mental health problems are prevalent in autistic youth, but the underpinning mechanisms are not well explored. In neurotypical youth, stressful life events are an established risk factor for mental health problems. This study tested longitudinal bidirectional associations between family-level stressful life events and mental health problems and whether these were moderated by cognitive flexibility, in a cohort of autistic children (N = 247). Family-stressful life events, assessed using the parent-reported Family Inventory of Life Events and Changes, and mental health problems, assessed using the teacher-reported Child Behavior Checklist Internalizing and Externalizing Symptoms subscales, were measured at multiple points between 7 and 11 years. Analyses showed no significant pathways from internalizing or externalizing symptoms to family-stressful life events or from family-stressful life events to internalizing or externalizing symptoms. There was some evidence of moderation by cognitive flexibility; the family-stressful life events to internalizing symptoms pathway was non-significant in the group with typical shifting ability but significant in the group with clinically significant shifting problems. Information about family-level stressful life event exposure and cognitive flexibility may be helpful in identifying autistic youth who may be at higher risk of developing mental health problems. Established risk factors for mental health problems in neurotypical populations are relevant for understanding mental health in autistic youth. [This article was written with the Pathways in ASD Study Team.]

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.

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.

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.

Despite considerable progress in characterizing the early signs of autism spectrum disorder (ASD), more remains to be learned about how symptoms emerge in the first year of life. Parents with a new baby who already had at least one biological child diagnosed with ASD (high-risk) or no family history of ASD (low-risk) completed two measures when their baby was 9 months of age, the Autism Parent Screen for Infants (APSI) questionnaire and the interview-based Parent Concerns Form. Children underwent a blinded independent diagnostic assessment for ASD at age 3 years. Total scores on the APSI and the Parent Concerns Form were both able to independently differentiate high-risk children who were later diagnosed with ASD from other high-risk and low-risk children who were not. Using logistic regression, we found that the total score on the APSI predicted ASD outcomes at age 3 with 70% accuracy, but the Parent Concerns Form did not contribute any unique variance when the APSI was already in the model. The results suggest that the APSI identifies early features predictive of ASD in high-risk infants and can be used to flag them for targeted follow-up and screening.

The objectives were to characterize behavioral signs of autism spectrum disorder (ASD) in younger siblings of diagnosed children (high-risk; HR) and examine classification features of the Autism Observation Scale for Infants (AOSI). Participants (501 HR and 180 low-risk [LR]) were assessed between 6 and 18 months using the AOSI and at age 3 for ASD diagnoses. Total AOSI scores differentiated HR infants later diagnosed with ASD starting at 12 months. ROC analyses identified 12- and 18-month cutoff scores associated with 0.52 sensitivity and 0.74 specificity and 0.73 sensitivity and 0.65 specificity, respectively. Although classification accuracy does not support use as a standalone screen, the AOSI identifies features associated with ASD starting at 6 months and differentiates HR infants with ASD by 12 months.

Temperament is a construct that is relatively stable over time but varies between individuals. Research suggests that children with autism spectrum disorder have a 'reactive' temperament profile when compared to peers with or without disabilities. However, our understanding of how temperament varies within children with autism and how it relates to child symptoms and outcomes is limited. This study aimed to: (1) explore the variation of individual temperament traits within a sample of school-aged children with autism to determine whether subgroups of children with similar trait profiles emerge; and (2) examine whether temperament influences the relationship between autism symptoms and adaptive functioning outcomes. Results revealed that children with autism can be classified empirically into two distinct profiles -- 'Even' and 'Reactive' temperaments. Correlational and hierarchical regression analyses indicated that both temperament profiles and baseline symptom severity predicted adaptive functioning outcomes 1 year later. There was a significant interaction between temperament and symptom severity, suggesting temperament can influence the impact of increasing symptom severity on adaptive functioning skills in children with autism. Study findings highlight the importance of considering temperament in understanding the individual differences that influence the development of daily functioning and developmental outcomes in children with autism.

This study investigated rates of suicidal ideation (SI) and suicidal and/or self-injurious behaviour (SSIB) reported by parents on the Child Behavior Checklist for 178 children with ASD over four annual assessments (ages 7-11 years). Analyses examined the frequency and persistence of SI and SSIB, and the association of SI and SSIB at any time point with child characteristics and internalizing and externalizing problems at age 7. SI occurred in 9.6% of children and was associated with fewer ASD symptoms and better adaptive functioning at age 7. SSIB occurred in 14.6% and was associated with poorer adaptive functioning and more externalizing behaviour at age 7. Internalizing problems were not associated with SI or SSIB at any time point. SI and SSIB rarely co-occurred (4%).

Background: Gender clinic and single‐item questionnaire‐based data report increased co‐occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under‐studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. Methods: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4–12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi‐dimensionally using a well‐validated parent‐report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex‐assigned‐at‐birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. Results: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC‐derived scores. Instead, higher early‐childhood dimensional autistic social‐communication traits correlated with higher current overall gender incongruence (as defined by GIQC‐14 score). This correlation was potentially moderated by sex‐assigned‐at‐birth: greater early‐childhood autistic social‐communication traits were associated with higher current overall gender incongruence in assigned‐males‐at‐birth, but not assigned‐females‐at‐birth. For fine‐grained gender diversity domains, greater autistic restricted‐repetitive behavior traits were associated with greater diversity in gender identity across sexes‐assigned‐at‐birth; greater autistic social‐communication traits were associated with lower stereotypical male expression across sexes‐assigned‐at‐birth. Conclusions: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early‐childhood autistic social‐communication traits and overall current gender diversity was most evident in assigned‐males‐at‐birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender‐diverse populations. [ABSTRACT FROM AUTHOR]

Social-emotional behavior in autism spectrum disorder (ASD) was examined among high-risk (HR; siblings of children diagnosed with ASD) and low-risk (LR; no family history of ASD) toddlers. Caregivers completed the Infant-Toddler Social Emotional Assessment (ITSEA) at 18 months, and blind diagnostic assessment for ASD was conducted at 36 months. Results indicated impairment in social-emotional functioning among HR toddlers subsequently diagnosed with ASD compared to other HR and LR toddlers, such that ITSEA domains (Internalizing, Dysregulation, Competence) and subdomains predicted later ASD symptoms and diagnosis. Receiver operating curves of optimal ITSEA cutoffs ranged from 0.23 to 0.44 for sensitivity, and 0.74 to 0.89 for specificity. Although classification accuracy for ASD was limited, group differences highlight the importance of considering social-emotional development when assessing ASD risk.

We report results from a large qualitative study regarding the process of parents "coming to understand the child has autism" starting from the time of initial developmental concerns. Specifically, we present findings relevant to understanding how parents become motivated and prepared for engaging in care at this early stage. The study included primary data from 45 intensive interviews with 32 mothers and 9 expert professionals from urban and rural regions of Ontario, Canada. Grounded theory methods were used to guide data collection and analysis. Parents' readiness (motivation and capacity) for engagement develops progressively at different rates as they follow individual paths of meaning making. Four optional steps account for their varied trajectories: "forming an image of difference," "starting to question the signs," "knowing something is wrong," and "being convinced it's autism." Both the nature of the information and professional help parents seek, and the urgency with which they seek them, evolve in predictable ways depending on how far they have progressed in understanding their child has autism. Results indicate the need for sensitivity to parents' varying awareness and readiness for involvement when engaging with them in early care, tailoring parent support interventions, and otherwise planning family-centered care pathways.

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.