Search

BackgroundHeterogeneous 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.MethodsUsing 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.ResultsClustering 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.LimitationsNotable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic.ConclusionsConcomitantly 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.

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.

For autistic young adults, deciding whether to disclose their autism at work is complex. Minimal research explores what they need to support disclosure and what influences decisions. To understand disclosure needs and influencers, we explored (i) disclosure decision-making experiences and (ii) perceptions of the disclosure process among autistic young adults. We conducted focus groups using the Capability, Opportunity, Motivation, Behaviour Model and Theoretical Domains Framework (TDF). We analyzed data from 23 participants and mapped onto the TDF to develop five themes: (1) workplace environment, (2) perceptions of disclosure outcomes, (3) personal factors and identity, (4) disclosure-related ambitions and determination, and (5) know-hows of disclosure. Future work should prioritize developing disclosure decision-making supports and investigate employer roles in fostering inclusive workplaces.

We examined pathways from pre-existing psychosocial and economic vulnerability to mental health difficulties and stress in families during the COVID-19 pandemic. Data from two time points from a multi-cohort study initiated during the COVID-19 pandemic were used. Parents of children 6-18 years completed questionnaires on pre-COVID-19 socioeconomic and demographic factors in addition to material deprivation and stress due to COVID-19 restrictions, mental health, and family functioning. Youth 10 years and older also completed their own measures of mental health and stress. Using structural equation modelling, pathways from pre-existing vulnerability to material deprivation and stress due to COVID-19 restrictions, mental health, and family functioning, including reciprocal pathways, were estimated. Pre-existing psychosocial and economic vulnerability predicted higher material deprivation due to COVID-19 restrictions which in turn was associated with parent and child stress due to restrictions and mental health difficulties. The reciprocal effects between increased child and parent stress and greater mental health difficulties at Time 1 and 2 were significant. Reciprocal effects between parent and child mental health were also significant. Finally, family functioning at Time 2 was negatively impacted by child and parent mental health and stress due to COVID-19 restrictions at Time 1. Psychosocial and economic vulnerability is a risk factor for material deprivation during COVID-19, increasing the risk of mental health difficulties and stress, and their reciprocal effects over time within families. Implications for prevention policy and parent and child mental health services are discussed., Author(s): Jala Rizeq [sup.1] , Daphne J. Korczak [sup.1] [sup.2] , Katherine Tombeau Cost [sup.1] , Evdokia Anagnostou [sup.3] [sup.4] , Alice Charach [sup.1] [sup.2] , Suneeta Monga [sup.1] [sup.2] [...]

Objective: Anxiety disorders are among the most common co-occurring conditions in autism spectrum disorder (ASD). Despite their prevalence and impact, there are no randomized controlled trials (RCTs) aimed at evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) for anxiolysis in this population, who may have a different biological basis for anxiety. Methods: Secondary analyses of the STAART double-blind, placebo-controlled RCT of citalopram in children with ASD examined whether citalopram reduced anxiety measured on the parent-reported Child and Adolescent Symptom Inventory-4 (CASI-4) as the primary outcome. An intention-to-treat analysis involving all 149 participants used multiple imputations for missing data and included baseline stratification factors of age group and site, among others. We prespecified as clinically significant a 33% reduction in anxiety in citalopram versus placebo, coinciding with 80% power. We tested whether communicative ability on the Vineland Communication score moderated treatment effect and explored whether initial anxiety was associated with greater adverse events, which could impact on dose titration and achieving optimal dose. Results: Both groups showed substantial reduction in anxiety. Citalopram was associated with a nonsignificant 16.5% greater reduction (observed coefficient = -0.181, bootstrap standard error = 0.126, p = 0.151, confidence interval = -0.428 to 0.066). Anxiety reports were significantly lower in children with reduced communicative ability, but communicative ability did not moderate the treatment effect (interaction p = 0.294). Initial anxiety levels were not associated with increased adverse effects (interaction ps 0.162-0.954). Conclusion: Citalopram did not statistically significantly improve anxiety in children with ASD. Clinicians should be cautious in their use of SSRIs for this indication. There remains a need for well-powered clinical trials testing the efficacy of SSRIs among autistic children with anxiety disorders.

In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research.

Examining brain and behaviour associations for language in autism spectrum disorder (ASD) may bring us closer to identifying neural profiles that are unique to a subgroup of individuals with ASD identified as language impaired (e.g. ASD LI+). We conducted a scoping review to examine brain regions that are associated with language performance in ASD. Further, we examined methodological differences across studies in how language ability was characterized and what neuroimaging methods were used to explore brain regions. Seventeen studies met inclusion criteria. Brain regions specific to ASD LI+ groups were found, however inconsistencies in brain and language associations were evident across study findings. Participant age, age-appropriate language scores, and neuroimaging methods likely contributed to differences in associations found.

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.

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.

Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.

Sensory-Based Interventions (SBIs) are often recommended to enable function/participation in children with ASD. Still, there are limited studies to evaluate their effectiveness. Acceptability studies are an important step towards establishing effective interventions. We examined parents' perceptions of the uptake and acceptability of such interventions. An online survey was sent to 399 families; response rate was 39%. The most frequently therapist-recommended interventions were trampoline (54.6%), massage (47.8%), and oral-motor tools (43.8%). Highest use was reported for massage (96.3%), trampoline (89.2%) and joint compressions and brushing (89.2%). The majority of parents viewed these interventions to be very important /important, (74.8%) but barriers to their use were identified. High acceptability of SBIs was reported by parents of children with ASD.

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.

Adolescents with autism spectrum disorder are less physically active compared with their age-related peers. Despite the many benefits of physical activity, little is known about why they are predominantly inactive. To date, research has rarely included adolescent's perspectives, and little is known about how wider social, systemic, and policy forces shape physical activity. The purpose of this study was to explore the perceptions, meanings, and role of physical activity in the lives of adolescents with autism spectrum disorder, and draw on their experiences to examine how social and cultural processes shaped their participation. Ten adolescent boys with autism spectrum disorder created individual digital stories, and participated in two interviews. Thematic analysis was informed by a critical social science approach. The results highlight that bullying, challenges in community programs, and the prioritization of therapeutic interventions limited participation. Participation was maximized when physical activity generated meaning, purpose, a sense of identity, and affective pleasures. The study findings illuminate the complexity of physical activity participation which has not previously been described in the literature. The findings suggest potential value in promoting the affective pleasures of movement, along with facilitating social and systemic pathways to enhance physical activity participation.

The underpinnings of mild to moderate neurodevelopmental delay remain elusive, often leading to late diagnosis and interventions. Here, we present data on exome and genome sequencing as well as array analysis of 13 individuals that point to pathogenic, heterozygous, mostly de novo variants in WDFY3 (significant de novo enrichment P = 0.003) as a monogenic cause of mild and non-specific neurodevelopmental delay. Nine variants were protein-truncating and four missense. Overlapping symptoms included neurodevelopmental delay, intellectual disability, macrocephaly, and psychiatric disorders (autism spectrum disorders/attention deficit hyperactivity disorder). One proband presented with an opposing phenotype of microcephaly and the only missense-variant located in the PH-domain of WDFY3. Findings of this case are supported by previously published data, demonstrating that pathogenic PH-domain variants can lead to microcephaly via canonical Wnt-pathway upregulation. In a separate study, we reported that the autophagy scaffolding protein WDFY3 is required for cerebral cortical size regulation in mice, by controlling proper division of neural progenitors. Here, we show that proliferating cortical neural progenitors of human embryonic brains highly express WDFY3, further supporting a role for this molecule in the regulation of prenatal neurogenesis. We present data on Wnt-pathway dysregulation in Wdfy3-haploinsufficient mice, which display macrocephaly and deficits in motor coordination and associative learning, recapitulating the human phenotype. Consequently, we propose that in humans WDFY3 loss-of-function variants lead to macrocephaly via downregulation of the Wnt pathway. In summary, we present WDFY3 as a novel gene linked to mild to moderate neurodevelopmental delay and intellectual disability and conclude that variants putatively causing haploinsufficiency lead to macrocephaly, while an opposing pathomechanism due to variants in the PH-domain of WDFY3 leads to microcephaly.

Examining brain and behaviour associations for language in autism spectrum disorder (ASD) may bring us closer to identifying neural profiles that are unique to a subgroup of individuals with ASD identified as language impaired (e.g. ASD LI+). We conducted a scoping review to examine brain regions that are associated with language performance in ASD. Further, we examined methodological differences across studies in how language ability was characterized and what neuroimaging methods were used to explore brain regions. Seventeen studies met inclusion criteria. Brain regions specific to ASD LI+ groups were found, however inconsistencies in brain and language associations were evident across study findings. Participant age, age-appropriate language scores, and neuroimaging methods likely contributed to differences in associations found., Author(s): Carly A. Cermak [sup.1] [sup.2] [sup.3] , Spencer Arshinoff [sup.3] , Leticia Ribeiro de Oliveira [sup.1] [sup.2] , Anna Tendera [sup.2] , Deryk S. Beal [sup.1] [sup.2] [sup.3] , [...]

Although autism spectrum disorder (ASD) is associated with significant mental health concerns, little is known about suicidality, particularly among youth. To address this critical gap in the literature, the current study examined the predictive validity of (1) demographics, (2) core autism symptoms, (3) cognitive abilities and adaptive behavior, (4) comorbid psychopathology, and (5) medical problems, for suicide-related behaviors among autistic youth (N = 481; M[subscript age] = 11.56 years). As indices of suicide-related behaviors, parents reported on whether the child had ever (1) talked about killing themselves, and (2) engaged in deliberate self-harm or attempted suicide. These two suicide-related outcomes had distinct clinical correlates, including child age, parental education, restricted and repetitive behaviors, IQ and adaptive behavior, affective and conduct problems, and medical concerns.

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]