Podcast: Autism means different things to different people

At this year’s International Society of Autism Research meeting in Austin, TX, there was a variety of themes explored. From early development and milestones, to intervention and supports, to different features like sensory issues, treatment, and how to solve the problem of heterogeneity. It comes down to this: Autism means different things to different people. This is just a small subset of everything that was presented at INSAR 2022 and I hope that if you want to see more, you advocate to have the presentations posted online or even have the program book made available publicly. In the meantime, enjoy the 30 minute summary here.

www.autism-insar.org

This week, the #ASFpodcast explores different types of interventions for which the core autism features are not necessarily the target, but those that enhance quality of life and provide help for irritability and emotional dysregulation. They include cooking, music therapies and antipsychotic medications. While they may not be effective in core autism features, they may help in other ways. Listen to the podcast here.

https://www.jaacap.org/article/S0890-8567(22)00198-8/fulltext

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004381.pub4/full

https://www.sciencedirect.com/science/article/abs/pii/S0891422222000890?via%3Dihub

This year’s first podcast dedicated to COVID issues explores both caregiver and clinician satisfaction with telehealth. New studies explore this satisfaction with assessment as well as psychiatric interventions. Also, as a follow up to the INSAR presentations on resiliency in mental health, a new study from Canada explains what may be at the core of this resiliency. Finally – why are some autistic people still not getting vaccinated? Listen to the podcast here.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126276/

https://pubmed.ncbi.nlm.nih.gov/35579789/

https://pubmed.ncbi.nlm.nih.gov/35575840/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088649/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023320/

Awareness of autism has grown monumentally over the past 20 years. Yet, this increased awareness has not been accompanied by improvements in services to support autistic individuals and their families. Many fundamental questions remain about the care of people with autism—including which interventions are effective, for whom, when, and at what intensity. The Lancet Commission on the future of care and clinical research in autism aims to answer the question of what can be done in the next 5 years to address the current needs of autistic individuals and families worldwide

Psychosis rates in autism spectrum disorder (ASD) are 5-35% higher than in the general population. The overlap in sensory and attentional processing abnormalities highlights the possibility of related neurobiological substrates. Previous research has shown that several electroencephalography (EEG)-derived event-related potential (ERP) components that are abnormal in schizophrenia, including P300, are also abnormal in individuals at Clinical High Risk (CHR) for psychosis and predict conversion to psychosis. Yet, it is unclear whether P300 is similarly sensitive to psychosis risk in help-seeking CHR individuals with ASD history. In this exploratory study, we leveraged data from the North American Prodrome Longitudinal Study (NAPLS2) to probe for the first time EEG markers of longitudinal psychosis profiles in ASD. Specifically, we investigated the P300 ERP component and its sensitivity to psychosis conversion across CHR groups with (ASD+) and without (ASD-) comorbid ASD. Baseline EEG data were analyzed from 304 CHR patients (14 ASD+; 290 ASD-) from the NAPLS2 cohort who were followed longitudinally over two years. We examined P300 amplitude to infrequent Target (10%; P3b) and Novel distractor (10%; P3a) stimuli from visual and auditory oddball tasks. Whereas P300 amplitude attenuation is typically characteristic of CHR and predictive of conversion to psychosis in non-ASD sample, in our sample, history of ASD moderated this relationship such that, in CHR/ASD+ individuals, enhanced – rather than attenuated – visual P300 (regardless of stimulus type) was associated with psychosis conversion. This pattern was also seen for auditory P3b amplitude to Target stimuli. Though drawn from a small sample of CHR individuals with ASD, these preliminary results point to a paradoxical effect, wherein those with both CHR and ASD history who go on to develop psychosis have a unique pattern of enhanced neural response during attention orienting to both visual and target stimuli. Such a pattern stands out from the usual finding of P300 amplitude reductions predicting psychosis in non-ASD CHR populations and warrants follow up in larger scale, targeted, longitudinal studies of those with ASD at clinical high risk for psychosis.

Keywords: EEG; P300; autism spectrum disorder; conversion; prodrome; psychosis.

The COVID-19 pandemic has disrupted autism research and services. Early career researchers (ECRs) are particularly vulnerable to the impact of the pandemic on job security and career development. The goal of this study was to capture the challenges ECRs are facing during the pandemic and the supports that are needed for career development and research. ECRs were invited to complete an online survey that focused on four major areas; the impact of COVID-19 on their research; changes in productivity due to COVID-19; changes to training due to COVID-19; and current mental health. 150 ECRs were eligible and provided sufficient data for inclusion. All but one ECRs reported their research had been negatively impacted by the pandemic. Reductions in productivity were reported by 85% of ECRs. The biggest impacts included recruitment of participants, increased needs at home and personal mental health. ECRs reported a 3-fold increase in burnout, as well as increased anxiety. ECR supports, such as funding, flexibility, and tenure extensions, are required to ensure ASD research does not suffer from a “lost generation” of researchers. LAY SUMMARY: The COVID-19 pandemic has had negative impacts on research around the world. Loss of productivity impedes autism research discoveries. However, researchers in the earliest phases of their career, specifically postdoctoral fellows through individuals in assistant professor (or equivalent) positions, are particularly vulnerable to long-lasting effects of pandemic-related disruptions which may limit their ability to continue as autism researchers. This survey highlights the needs of this group and identifies mechanisms by which these early career researchers may be supported in this time. This is critical to ensure the next generation of ASD researchers and clinician scientists continue on the path to advancing understanding of autism in the decades to come.

Keywords: COVID-19; autism research; early career researchers.

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.

While much research has examined the development of facial recognition abilities, less is known about the ability of individuals with and without autism to categorize facial gender. The current study tested gender categorization abilities in high-functioning children (5-7 and 8-12 years), adolescents (13-17 years), and adults (18-53 years) with autism and matched controls. Naturalistic videos depicted faces that were either typical or less typical of each gender. Both groups improved in their performance across development. However, control children reached expertise that was similar to control adults by 8-12 years; whereas, adults with autism never reached this level of expertise, particularly with less typical gender faces. Results suggest that individuals with autism employ different face processing mechanisms than typically developing individuals.

2013University of California DavisEzzat HashemiVeronica Martinez-Cerdeno

2014University of North CarolinaDara Chan