Conference proceedings: Inaugural meeting of the consortium for autism, genetic neurodevelopmental disorders, and digestive diseases

Objectives: Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), often experience a higher prevalence of gastrointestinal (GI) symptoms but have complex medical and behavioral comorbidities that make diagnosis and treatment difficult. A multi-stakeholder conference was convened to (a) determine patient and family experiences related to GI symptoms in NDDs, (b) review the clinicians’ and researchers’ perspectives, and (c) determine actionable steps for future research.

Methods: The Consortium for Autism, Neurodevelopmental Disorders and Digestive Diseases (CANDID; www.candidgi.com) virtually over 2 days in 2022 and consisted of four key activities: (1) an electronic family survey to assess underlying NDDs and GI symptoms, (2) a session focused on family perspectives, (3) review current clinical care and research, and (4) discussion to identify key next steps. Survey results were obtained electronically via the REDCap platform, and descriptive statistics were generated. The sessions were recorded, and themes were identified.

Results: The pre-conference survey ran for ~2 months and 739 families provided responses, with 634 completing all items. 83% had a child with an NDD under age 18, and most patients were White (85%) and non-Hispanic (87%). Constipation (80%), GI reflux disease (51%), and bloating (49%) were the most frequently reported symptoms. Families gave unstructured feedback that the measures used in the surveys were often difficult to answer for patients with NDDs or who were nonspeaking. Family and clinical/scientific sessions identified several common themes, including (1) the need for less invasive diagnostic modalities, (2) the need to validate or adapt existing diagnostic measures (e.g., the Rome IV criteria) and outcome assessments, and (3) the need for enhanced attention to parent and caregiver input in treatment plans.

Conclusions: Those providing care to children with NDDs, especially those with communication and cognitive challenges, should be aware of the differing needs in this community and consider family perspectives in managing, treating, and measuring GI issues. Future research should focus on adapting or creating diagnostic and research measures for those with NDDs, developing new diagnostic methods to account for diversity in neurodevelopment and communication, and improving methods for family and caregiver engagement in the care of GI disorders.

Profound autism refers to a subset of individuals with autism spectrum disorder who have an intellectual disability with an intelligence quotient less than 50 and minimal-to-no language and require 24-hour supervision and assistance with activities of daily living. The general pediatrician will invariably work with autistic children across the spectrum and will likely encounter youth with profound autism. Awareness of profound autism as a real entity describing autistic children with concomitant intellectual disability and language impairment who require 24-hour care is the first step in developing a solid pediatric home for these youth.

Autism spectrum disorder (ASD) is a heterogeneous condition that affects development and functioning from infancy through adulthood. Efforts to parse the heterogeneity of the autism spectrum through subgroups such as Asperger’s and Profound Autism have been controversial, and have consistently struggled with issues of reliability, validity, and interpretability. Nonetheless, methods for successfully identifying clinically meaningful subgroups within autism are needed to ensure that research, interventions, and services address the range of needs experienced by autistic individuals. The purpose of this study was to generate and test whether a simple set of questions, organized in a flowchart, could be used in clinical practice and research to differentiate meaningful subgroups based on individuals’ level of functioning. Once generated, subgroups could also be compared to the recently proposed administrative category of Profound Autism and to groupings based on standardized adaptive measures. Ninety-seven adults with autism or related neurodevelopmental disorders participating in a longstanding longitudinal study, or their caregivers if they could not answer for themselves, completed phone interviews when the participants were ~30 years old. Information from these phone interviews was used to generate vignettes summarizing characteristics and aspects of the daily lives of each participant (e.g., language level, vocational activities, and social relationships). Three expert clinicians then used these vignettes to classify each participant based on their level of support needs. Meaningfully distinct subgroups within the sample were identified which could be reliably distinguished from one another. Implications of such categorizations and future directions are discussed.

Are you the grandparent, cousin, aunt, uncle, sibling, or half-sibling of someone with autism and wondered “what is the likelihood of autism in families, and the likelihood of comorbid conditions if I have a family member with autism?” Listen to this week’s podcast. Researchers at the AJ Drexel Autism Research Institute and Aarhus University in Denmark collaborated to calculate probabilities between autism in a person and dozens of other comorbid conditions in family members. They not only made the paper open to the public for everyone to read it, but they also created a publicly available data visualization tool so anyone can go on and look at specific situations of particular family relationships relating to anything from autoimmune conditions to mental health and psychiatric diagnosis. Links below for reference:

https://pubmed.ncbi.nlm.nih.gov/39283002

Interactive graphs: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots_16918786403110/e-Figure5

Despite many years fighting it, families with autism still experience societal stigma. The experiences depend on many factors, summarized in the October 21st podcast. This week, Mia Kotikovski explores cultural factors involved in stigma. As examples, she explores the literature from Asia, the Middle East and the United Kingdom, how they are different, and how families cope with that stigma in different areas of the world.

https://link.springer.com/article/10.1007/s40489-023-00373-7

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330163

https://link.springer.com/article/10.1007/s10803-019-04218-3

https://www.nature.com/articles/s41598-022-23978-0

https://molecularautism.biomedcentral.com/articles/10.1186/s13229-023-00579-w

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261774

https://onlinelibrary.wiley.com/doi/full/10.1002/aur.2652

Animal models of autism, including cell based models, have received criticism because autism is a uniquely human condition so there is no value in studying it in a model like a mouse or a cell. On the other hand, model systems have been used for decades to develop therapies for a myraid of other conditions and disorders, and produced evidence-based treatments for not just autism but conditions from ADHD to schizophrenia. So why is there so much backlash about this line of research? The ASF podcast talks to Jill Silverman at UC Davis to get some perspective.

https://pubmed.ncbi.nlm.nih.gov/35285132

https://www.vox.com/future-perfect/377739/autism-research-mice-lab-models

In this week’s podcast episode, part 1 in cultural stigma around autism with Mia Kotikovski provides an overview of stigma, where it can come from across cultures and provides some examples of stigma in different countries. Different areas of the world are in different places in terms of their perceptions of autism, their needs for autism families, and what they perceive as their greatest difficulties. The topic is so important we broke it down into two sections. Please listen to both, it will explain a lot about autism services and supports around the world.

https://journals.sagepub.com/doi/10.1177/1362361318823550

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992913

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303671

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303671

https://pubmed.ncbi.nlm.nih.gov/30248583

https://pubmed.ncbi.nlm.nih.gov/38507392

https://www.researchgate.net/publication/277816405_A_Cross-Cultural_Comparison_of_Knowledge_and_Stigma_Associated_with_Autism_Spectrum_Disorder_Among_College_Students_in_Lebanon_and_the_United_States?enrichId=rgreq-97b7d5f50aac4d5b124ea8295b42fdb0-XXX&enrichSource=Y292ZXJQYWdlOzI3NzgxNjQwNTtBUzoyNDI4NTI2Mzk4NDIzMDRAMTQzNDkxMTk4OTI3MA%3D%3D&el=1_x_3&_esc=publicationCoverPdf

Ensuring children are safe during the night can be a major concern for autism families. Up to 80% of children with autism experience sleep disturbances, and caregivers express concern about elopement, self-injury, and other risks that may be incurred by a child who has difficulty sleeping through the night. Safeguarding against these risks can be challenging and lead to many sleepless nights for the parents as well as the child. This project will use data gathered through remote interviews and daily sleep diaries to adapt a newly formed questionnaire that can be validated and used as a quantitative measure of caregivers’ safety-related concerns. There will be a special focus on the concerns of underrepresented groups such as families of color, those from socioeconomically disadvantaged communities, and families supporting children with additional disabilities. Additionally, objectively measured sleep data from a larger existing study will be used to assess how caregiver safety concerns relate to the actual sleep patterns of both the child and caregiver. The ability to document and measure safety-related concerns in diverse communities and identify sleep patterns linked to these concerns will lead to better understanding and more effective targeting of the specific needs of families.

Many parents of older autistic children look back and recall that their children experienced eating and feeding problems during infancy. These challenges negatively impacted their child’s quality of life resulting in issues from stomach pain to malnutrition. This study will examine feeding and eating behaviors in infants as early as 6 months old with a family history of either autism or ADHD. These infants will be followed to toddlerhood to determine if eating and feeding problems can contribute to early prediction of autism. The goals of this research are to determine if early eating difficulties are a sign of autism and if they are specific to autism, as well as how best to treat these issues early in children likely to be diagnosed with autism.

On this week’s podcast episode, special correspondent Mia Kotikovski discusses challenges in getting emergency care for those with autism, what doctors and hospitals can do to ease the stressors associated with places like the ER. This is a huge issue for families as many “simple” ER visits for their autistic family members can cause such stress it provokes severe reactions, especially in those with sensory issues, intellectual disability or those who cannot express their pain.

https://publications.aap.org/pediatrics/article/137/Supplement_2/S205/34011/Toward-Practice-Advancement-in-Emergency-Care-for

Instead of grouping together people with autism based on traditional severity scores, what if groupings were done based on functional outcome? Would this help better understand the broad spectrum of autism and why some people with autism are so different than others? Researchers at the University of Minnesota led by Kyle Sterrett, together with UCLA and UNC utilized a study that followed children with autism in the early 1990’s into their adulthood, in the 2020’s. They created and asked these families a set of questions (included in the manuscript below) to help identify levels of functioning in people with autism. This was done to help them and their families get the right support at right time. They found that these questions could differentiate people with Profound Autism based on things like level of independence and safety concerns. Dr. Sterrett talks with us on this week’s podcast to explain what they did and why it is so important.

https://pubmed.ncbi.nlm.nih.gov/39031157

During sleep, your brain is still active. It is turning all those things you learned during the day into long term memories through connections between the thalamus, hippocampus and frontal cortex. What happens in Profound Autism? How does the brain work during sleep and how will this knowledge lead to better sleep in people? Are there interventions already underway that are being tested that target sleep brainwaves? It can be hard to measure sleep, so in Part 2 of the Profound Autism Series, Dr. Dimitrios Mylonas from Harvard talks about his study to use portable home brain activity monitors that have been adapted for use in Profound Autism and an intervention based on this brain activity is being tested in other disorders. His study is now enrolling and is all remote, if you are interested in participating please email him at: DMYLONAS@mgh.harvard.edu