Barriers to Healthcare for Latinx Autistic Children and Adolescents.

PURPOSE: To understand the ways in which autistic Latinx children experience disparities in diagnosis, healthcare, and receipt of specialty services. METHODS: 417 individuals who identified as Latinx caregivers of autistic children who were members of the same integrated healthcare system in Northern California were surveyed. Responses were analyzed using the child's insurance coverage (Government or Commercial) and caregiver's primary language (Spanish or English). RESULTS: Compared to the commercially-insured, government-insured participants accessed several services at a higher rate and were less likely to cite the high cost of co-pays as a barrier. CONCLUSION: There were no significant differences in service access by language status, but Spanish speakers were more likely to cite health literacy as a barrier to receiving care.

Self-Report Measurement of Well-Being in Autistic Adults: Psychometric Properties of the PERMA Profiler.

Background: Studies of positive psychology and emotional well-being have broadened our understanding of mental health. However, mental health research involving autistic adults has been largely deficit-focused. Few studies have examined well-being using established positive psychological frameworks. Methods: This study examined the psychometric characteristics of the PERMA Profiler, a 23-item questionnaire that measures well-being across five subscales (Positive emotion, Engagement, Relationships, Meaning, and Accomplishment), in a sample of 517 autistic adults ages 18-84 years (M = 39.5, standard deviation [SD] = 13.3). Reliability (internal consistency), structural validity (via confirmatory factor analysis including bifactor modeling), and concurrent validity were examined. Results: The PERMA Profiler mean (SD) well-being score was 5.4 (SD = 1.7), which is notably lower than the mean of 7.0 previously found in nonautistic samples. Subscale scores were highest for Engagement (M = 6.8; SD = 1.9), followed by Accomplishment (M = 5.6; SD = 2.2), Relationships (M = 5.2; SD = 2.6), Meaning (M = 5.2; SD = 2.7), and Positive emotion (M = 5.0; SD = 2.4). Factor analyses revealed strong psychometrics (Cronbach's α = 0.93; Comparative Fit Index = 0.94; Tucker-Lewis Index = 0.97; root mean square error of approximation = 0.08; standardized root mean residual = 0.05) and superior fit of the bifactor model, supporting a general factor for conceptualizing well-being as opposed to a five-factor model. PERMA well-being and subscale scores were significantly correlated (p < 0.001) with mental health conditions and life satisfaction. Conclusion: These findings support use of an adapted version of the PERMA Profiler in mental health research to evaluate well-being among autistic adults. Similar to studies with nonautistic populations, the Engagement measure may not capture the experiences of the autistic population and further refinement is needed. Follow-up research should represent a more diverse autistic population, collaborate with autistic coinvestigators, and explore potential correlates of well-being (such as social stigma) while using the PERMA Profiler.

Why is this an important issue?: "Well-being" captures a state of comfort, health, and happiness and is more than just the absence of disease or negative feelings. Only a few studies to date have focused on the emotional well-being of autistic adults. The positive psychology-based PERMA Profiler (named after the five subscales: Positive emotions, Engagement, Relationships, Meaning, and Accomplishment) is a brief self-report measure for rating well-being using 23 questions. It has been widely used for studying well-being in nonautistic populations. However, no studies have tested how well the PERMA Profiler measures well-being among autistic adults. What was the purpose of this study?: The goal was to evaluate the PERMA Profiler using data from a group of autistic adults living in the United States. This was the first study that tested how well the PERMA Profiler measures the well-being of autistic adults, both overall and across the five subscales. What did the researchers do?: First, we collected responses to the PERMA Profiler and other questions from more than 500 autistic adults. Then, we tested whether the PERMA Profiler measures well-being consistently and if the measure performs as expected (i.e., did it measure what it is supposed to measure?). We also compared well-being scores with the mental health (anxiety and depression) and life satisfaction of the study participants. What were the results of the study?: The average overall well-being score was 5.4 out of 10, with higher values indicating experiencing well-being more often. Notably, the average well-being score was 7.0 in unrelated, previous studies of nonautistic adults). The PERMA Profiler measured well-being consistently in our sample. The overall well-being scores and each of the five subscale scores were related to mental health and life satisfaction as expected. The "Engagement" subscale did not perform as well as the others in our sample, which was consistent with the findings of studies with nonautistic adults. What do these findings add to what was already known?: This is the first study to evaluate the effectiveness of the PERMA Profile or any measure of self-reported well-being in a sample of autistic adults. These results can help future researchers determine how best to study well-being, specifically in autistic adults. These findings point to important changes that might be made to the PERMA Profiler before it is used in future research. What are potential weaknesses in the study?: Autistic adults were not involved in the development of the PERMA Profiler. Therefore, the measure may need to be changed by teams involving autistic coinvestigators before use with other samples. Second, our findings may not represent larger, more diverse groups of autistic adults because most participants were White (85%), well-educated (more than 80% completed at least some college), and did not have intellectual disability. Lastly, the study was conducted during the COVID-19 pandemic, which likely impacted the well-being of participants. How will these findings help autistic adults now or in the future?: Our study provides preliminary support for the PERMA Profiler and suggests next steps for improving it and other measures of well-being before expanding use with autistic adults. Our findings may help the field of autism research develop new measures for understanding and improving well-being. The strengths and weaknesses of the PERMA Profiler that we identified can inform future strengths-based research involving autistic adults.

Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism.

BACKGROUND: Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. RESULTS: We use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence. CONCLUSIONS: Together, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.

Exploring a Role for Parental Mental Health in Perception and Reports of Pain on Behalf of Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) have a higher prevalence of pain compared to those without ASD. Pain is a leading cause of morbidity and disability worldwide and may contribute to adverse health outcomes in people with ASD, thus warranting further research on this special population. The present study used data from 1,423 children with ASD and 46,023 children without ASD and their mothers from the combined 2016-2017 National Survey of Children's Health. Mothers reported child pain and ASD status and their own mental health status. Mothers reporting a status of "Fair or Poor" were considered as having maternal mental health conditions (MMHCs) for the purposes of this study. Children with and without ASD who had mothers with MMHCs had higher odds of pain compared to children with mothers without MMHCs. These increased odds did not attenuate as a result of controlling for co-occurring neurological conditions, which have been associated with increased pain in children with ASD. Thus, parent mental health may alter perception and/or reports of pain on behalf of children with and without ASD. Future research should include more detailed assessments of parent mental health and clinical assessments of children in order to explore the role of parent mental health in the experiences of pain and other symptoms present in children with ASD.

Functional genomics analysis of Phelan-McDermid syndrome 22q13 region during human neurodevelopment.

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by varying degrees of intellectual disability, severely delayed language development and specific facial features, and is caused by a deletion within chromosome 22q13.3. SHANK3, which is located at the terminal end of this region, has been repeatedly implicated in other neurodevelopmental disorders and deletion of this gene specifically is thought to cause much of the neurologic symptoms characteristic of PMS. However, it is still unclear to what extent SHANK3 deletions contribute to the PMS phenotype, and what other genes nearby are causal to the neurologic disease. In an effort to better understand the functional landscape of the PMS region during normal neurodevelopment, we assessed RNA-sequencing (RNA-seq) expression data collected from post-mortem brain tissue from developmentally normal subjects over the course of prenatal to adolescent age and analyzed expression changes of 65 genes on 22q13. We found that the majority of genes within this region were expressed in the brain, with ATNX10, MLC1, MAPK8IP2, and SULT4A1 having the highest overall expression. Analysis of the temporal profiles of the highest expressed genes revealed a trend towards peak expression during the early post-natal period, followed by a drop in expression later in development. Spatial analysis revealed significant region specific differences in the expression of SHANK3, MAPK8IP2, and SULT4A1. Region specific expression over time revealed a consistently unique gene expression profile within the cerebellum, providing evidence for a distinct developmental program within this region. Exon-specific expression of SHANK3 showed higher expression within exons contributing to known brain specific functional isoforms. Overall, we provide an updated roadmap of the PMS region, implicating several genes and time periods as important during neurodevelopment, with the hope that this information can help us better understand the phenotypic heterogeneity of PMS.