The Autism Phenome Project: Toward Identifying Clinically Meaningful Subgroups of Autism

One of the most universally accepted facts about autism is that it is heterogenous. Individuals diagnosed with autism spectrum disorder have a wide range of behavioral presentations and a variety of co-occurring medical and mental health conditions. The identification of more homogenous subgroups is likely to lead to a better understanding of etiologies as well as more targeted interventions and treatments. In 2006, we initiated the UC Davis MIND Institute Autism Phenome Project (APP) with the overarching goal of identifying clinically meaningful subtypes of autism. This ongoing longitudinal multidisciplinary study now includes over 400 children and involves comprehensive medical, behavioral, and neuroimaging assessments from early childhood through adolescence (2–19 years of age). We have employed several strategies to identify sub-populations within autistic individuals: subgrouping by neural, biological, behavioral or clinical characteristics as well as by developmental trajectories. In this Mini Review, we summarize findings to date from the APP cohort and describe progress made toward identifying meaningful subgroups of autism.

Developmental trajectories of school-beginner’s ability self-concept, intrinsic value, and performance in mathematics

This study investigated the developmental interdependence of Finnish school-beginners’ (N = 285) ability self-concept, intrinsic value, and performance in mathematics. More specifically, we examined: (i) whether and how children’s ability self-concept and intrinsic value in mathematics change over their first three years in school, (ii) how those changes are related to each other, (iii) how they predict later math performance, and (iv) whether there are gender differences in these trajectories. The results showed significant decrease over time in children’s ability self-concept and intrinsic value, but also significant individual differences in the trajectories. The high dependency between the levels and changes in children’s self-concept and intrinsic value led us to specify a factor-of-curves latent growth model, thus merging the trajectories of ability self-concept and intrinsic value into one common model (i.e., math motivation). The subsequent results showed prior math performance to predict change in children’s math motivation, meaning that higher initial competence was connected with less steep decrease in motivation. After controlling for the effects of first-grade math performance, both the level and change in math motivation predicted third-grade math performance and teacher-rated grades. That is, higher initial motivation and less steep decrease in it independently predicted better later math competence. Boys reported less steep decrease in math motivation than girls, despite no gender differences in initial math performance.

Developmental origins of cell heterogeneity in the human lung

The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

Joint and independent effects of maternal prenatal depression and SARS-CoV-2 exposure on infant cognitive and socioemotional development across the first postnatal year

Here we evaluate longitudinal neurodevelopmental trajectories across the first postnatal year in infants of mothers impacted by the COVID-19 pandemic during pregnancy. Ninety-three pregnant mothers were recruited beginning at the first peak of the pandemic in New York City, and were oversampled for SARS-CoV-2 exposure during pregnancy (n = 36 COVID-19 exposed mothers). At 6 months postpartum, infant attentional processing was measured remotely using an online webcam-linked eye tracker developed for infant remote research in the home environment. At 12 months, infant socioemotional development was evaluated through maternal-report using validated surveys. Results indicated that interactions between maternal depressive symptoms and SARS-CoV-2 exposure during pregnancy were linked with individual differences in infants’ attentional processing at 6 months of age. Specifically, in mothers reporting positive exposure to SARS-CoV-2, higher prenatal depressive symptoms were associated with attentional patterns characterized by increased orienting to salient stimuli, longer looking times, and lower levels of maternal-reported measures of attentional control. In turn, these attentional patterns subsequently predicted socioemotional competence at 12 months, over and beyond individual contributions of prenatal depression, SARS-CoV-2 exposure, or relevant infant or family characteristics. These findings provide preliminary evidence of phenotypic adaptations in attentional processing by infants of mothers affected by the COVID-19 pandemic, and highlight infant attentional processing as a relevant early behavioral predictor of longitudinal developmental trajectories.

scDIOR: single cell RNA-seq data IO software

Background Single-cell RNA sequencing is becoming a powerful tool to identify cell states, reconstruct developmental trajectories, and deconvolute spatial expression. The rapid development of computational methods promotes the insight of heterogeneous single-cell data. An increasing number of tools have been provided for biological analysts, of which two programming languages- R and Python are widely used among researchers. R and Python are complementary, as many methods are implemented specifically in R or Python. However, the different platforms immediately caused the data sharing and transformation problem, especially for Scanpy, Seurat, and SingleCellExperiemnt. Currently, there is no efficient and user-friendly software to perform data transformation of single-cell omics between platforms, which makes users spend unbearable time on data Input and Output (IO), significantly reducing the efficiency of data analysis. Results We developed scDIOR for single-cell data transformation between platforms of R and Python based on Hierarchical Data Format Version 5 (HDF5). We have created a data IO ecosystem between three R packages (Seurat, SingleCellExperiment, Monocle) and a Python package (Scanpy). Importantly, scDIOR accommodates a variety of data types across programming languages and platforms in an ultrafast way, including single-cell RNA-seq and spatial resolved transcriptomics data, using only a few codes in IDE or command line interface. For large scale datasets, users can partially load the needed information, e.g., cell annotation without the gene expression matrices. scDIOR connects the analytical tasks of different platforms, which makes it easy to compare the performance of algorithms between them. Conclusions scDIOR contains two modules, dior in R and diopy in Python. scDIOR is a versatile and user-friendly tool that implements single-cell data transformation between R and Python rapidly and stably. The software is freely accessible at https://github.com/JiekaiLab/scDIOR.

Trajectories of imitation skills in preschoolers with autism spectrum disorders

Background Imitation skills play a crucial role in social cognitive development from early childhood. Many studies have shown a deficit in imitation skills in children with autism spectrum disorders (ASD). Little is known about the development of imitation behaviors in children with ASD. This study aims to measure the trajectories of early imitation skills in preschoolers with ASD and how these skills impact other areas of early development. Methods For this purpose, we assessed imitation, language, and cognition skills in 177 children with ASD and 43 typically developing children (TD) aged 2 to 5 years old, 126 of which were followed longitudinally, yielding a total of 396 time points. Results Our results confirmed the presence of an early imitation deficit in toddlers with ASD compared to TD children. The study of the trajectories showed that these difficulties were marked at the age of 2 years and gradually decreased until the age of 5 years old. Imitation skills were strongly linked with cognitive and language skills and level of symptoms in our ASD group at baseline. Moreover, the imitation skills at baseline were predictive of the language gains a year later in our ASD group. Using a data-driven clustering method, we delineated different developmental trajectories of imitation skills within the ASD group. Conclusions The clinical implications of the findings are discussed, particularly the impact of an early imitation deficit on other areas of competence of the young child.

Neurodevelopmental Trajectories Following Prenatal Alcohol Exposure

Prenatal alcohol exposure (PAE) interferes with neurodevelopment. The brain is particularly susceptible to the adverse consequences of prenatal alcohol exposure, and numerous studies have documented changes to brain anatomy and function, as well as consequences for cognition, behavior, and mental health. Studies in typically developing individuals have shown that the brain undergoes dynamic developmental processes over an individual’s lifespan. Furthermore, magnetic resonance imaging (MRI) studies in other neurodevelopmental and psychiatric disorders have shown that their developmental trajectories differ from the typical pattern. Therefore, to understand long-term clinical outcomes of fetal alcohol spectrum disorders (FASD), it is necessary to investigate changes in neurodevelopmental trajectories in this population. Here we review studies that have used MRI to evaluate changes in brain structure and function over time via cross-sectional or longitudinal methods in individuals with PAE. Research demonstrates that individuals with PAE have atypical cortical and white matter microstructural developmental trajectories through childhood and adolescence. More research is needed to understand how factors such as sex and postnatal experiences may further mediate these trajectories. Furthermore, nothing is known about the trajectories beyond young adulthood.

Psychological and Neural Differences of Music Processing in Autistic Individuals: A Scoping Review

Despite abundant research and clinical evidence of the effectiveness of music interventions for people in the autism spectrum, understanding of music processing in this community is limited. We explored whether research evidence of differences in music processing within the autistic community is available. We developed a scoping review to search for literature with the terms “music”, “processing,” and “autism” (and variants). We searched PubMed, CINAHL, Scopus, Web of Science, PsycInfo, Academic Search Complete, ERIC, and Music Index databases for a total of 10,857 articles, with 5,236 duplicates. The remaining 5,621 titles and abstracts were screened for eligibility by a team of four undergraduate and graduate students and the PI. Seventy-five studies were included for data extraction. Data were analyzed with descriptive statistics regarding author, study, stimulus, and participant information, and a thematic analysis of outcome and findings. Our findings are preliminary given the emerging nature of the literature, the use of mostly non-musical auditory stimuli, passive listening experiences, and underreported demographics. However, the literature shows some evidence of differences in music processing for autistic individuals, including reduced habituation to non-musical and musical stimuli; truncated, delayed, or divergent developmental trajectories; and possible compensatory higher-order mechanisms that yield similar behavioral responses even in the presence of divergent neural correlates. Music therapists are encouraged to adopt a developmental perspective, not only of general skills, but specifically of music skill development in this community, and to extrapolate these findings with caution, given the current limitations in the evidence.