Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis.

Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.

Relational victimization prospectively predicts increases in error-related brain activity and social anxiety in children and adolescents across two years.

Recent research has focused on identifying neural markers associated with risk for anxiety, including the error-related negativity (ERN). An elevated ERN amplitude has been observed in anxious individuals from middle childhood onward and has been shown to predict risk for future increases in anxiety development. The ERN is sensitive to environmental influences during development, including interpersonal stressors. Of note, one particular type of interpersonal stressor, relational victimization, has been related to increases in anxiety in adolescents. We tested whether relational victimization predicts increases in the ERN and social anxiety symptoms across two years in a sample of 152 child and adolescent females (ages 8 - 15). Results indicated that children and adolescents' baseline ERN was positively related to the ERN two years later. Furthermore, greater relational victimization at baseline predicted greater increases in the ERN two years later, controlling for baseline ERN. Moreover, relational victimization at baseline predicted increases in social anxiety, and this relationship was mediated by increases in the ERN. These results suggest that relational victimization impacts the developmental trajectory of the neural response to errors and thereby impacts increases in social anxiety among children and adolescents.

Associations between sleep problems and domains relevant to daytime functioning and clinical symptomatology in autism: A meta-analysis.

Autistic individuals experience significantly higher rates of sleep problems compared to the general population, which negatively impacts various aspects of daytime functioning. The strength of associations across domains of functioning has not yet been summarized across studies. The present meta-analysis examined the strength of associations between sleep problems and various domains of daytime functioning in autistic individuals. Searches were conducted in EMBASE, PubMed, Web of Science, and Google Scholar through May 2020. Inclusion criteria were: an index of sleep disturbance in individuals diagnosed with autism spectrum disorder (ASD); data collected prior to any sleep-related intervention; statistical data indicating relations between sleep problems and outcomes relevant to behavior, cognition, and physical or mental health. Exclusion criteria were: statistics characterizing the relationship between sleep disturbance and outcome variables that partialled out covariates; studies examining correlations between different measures of sleep disturbance. Participants totaled 15,074 from 49 published articles and 51 samples, yielding 209 effect sizes. Sleep problems were significantly associated with more clinical symptomatology and worse daytime functioning. Subgroup analyses demonstrated that sleep problems were most strongly associated with internalizing and externalizing symptoms and executive functioning, followed by core autism symptoms, family factors, and adaptive functioning. Findings highlight the far-reaching consequences of sleep problems on daytime functioning for autistic individuals and support the continued prioritization of sleep as a target for intervention through integrated care models to improve wellbeing. LAY SUMMARY: Autistic individuals experience higher rates of sleep problems, such as difficulty falling asleep and staying asleep, compared to the general population. We quantitatively summarized the literature about how sleep problems are related to different aspects of daytime functioning to identify areas that may be most affected by sleep. Sleep problems were related to all areas assessed, with the strongest associations for mood and anxiety symptoms. We recommend prioritizing sleep health in autistic individuals to improve wellbeing and quality of life.