Resilience and heterogeneity in ASD

Everyone knows that every person with autism has their own unique strengths and challenges. Autism is heritable, and there are over 100 genes associated with autism. There are also an unknown number of environmental factors influencing outcome, so the heterogeneity is not necessarily surprising. But why would two people with the same genetic mutation have variable outcomes? Researchers led by the Institut Pasteur in France looked at the range of outcomes in people with a rare genetic mutation associated with autism, focusing on those without an autism diagnosis. This week’s podcast is an interview with the lead author of the paper, Thomas Rolland, PhD from France. The presence of the variants in those without ASD were associated with lowered cognitive ability, education level and employment status. The bottom line of these finds are that genes affect proteins which form the brain and control brain function. However, there are multiple factors that influence outcome. Some of them may be sex or gender, prenatal exposures. It’s not just one thing, there are many things influencing an autism diagnosis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353945/pdf/41591_2023_Article_2408.pdf

A potential biomarker to AID, not MAKE, a diagnosis

The media has just called another biological marker a “diagnostic test”, when in this case, it was always intended to be an aid, not a test itself. It involves using baby hair strands to look a variation in metabolism of certain chemical elements across time. Remarkably, it showed similar results in autistic children in Japan, the US and Sweden. It’s not ready to be used as a diagnostic test, so what is it supposed to do? Listen to an interview with the inventor and researcher, Dr. Manish Arora from The Icahn School of Medicine at Mt. Sinai School here.

The full article (open access) can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740182/

Genetic confounding plus organoids

You heard it in the news this week, and we discuss it on this week’s ASF podcast. Can you make little brains in a dish then make them better by providing them a real structured live neural environment? Can these organoids integrate with a live brain and be functional in vivo? The answers are: yes! Learn more from a new study published this week. Also, what the h**l is genetic confounding and how can it address many of the controversies of genetic vs. the environment? Sometimes genes that predispose to a disorder also predispose to environmental factors leading to that disorder. There is always room for both. Here are the links I promised:

https://www.fhi.no/en/studies/moba/

https://pubmed.ncbi.nlm.nih.gov/35793100/

https://www.nature.com/articles/s41586-022-05277-w

A new ways for the environment to affect genetic expression

You have maybe heard about how environmental exposures after conception or birth may affect genetic expression and then risk of developing autism. But what research has been done to look at preconceptional exposures, presumably exposures that affect the cells that then give rise to sperm and eggs? Turns out they are susceptible to some environmental exposure too, which could lead to a change in the way genes are expressed in the embryo, the fetus, and then the child. Want to know more? Jill Escher just published a study with scientific colleagues about this hypothesis and she explains it in this week’s podcast.

https://pubmed.ncbi.nlm.nih.gov/34596807/

What causes autism? Genetics or the Environment? Or maybe both?

Is it genes or is it the environment? or is it a combination? This question has plagued researchers and scientists and caused a lot of confusion in families about what caused their own or their child’s ASD. This week we review the mechanisms by which de-novo mutations could be the work of gene x environment interactions, and share new evidence of how SSRI’s do or don’t contribute to ASD through gene x environment interactions. We also want to recognize the valuable work of scientist Li-Ching Lee to these efforts. Dr. Lee recently passed away but will be sorely missed.

https://pubmed.ncbi.nlm.nih.gov/34002022/

https://pubmed.ncbi.nlm.nih.gov/34116791/

Happy New Year – reasons to be excited for 2021

Welcome to 2021! Over the holiday break, autism researchers were busy coming up with answers to important questions: 1) how does an environmental exposure relevant to ASD change gene expression and 2) does Telehealth work and for whom? The first question was addressed by an ASF undergraduate who published in Nature. He is going to go on to do great things.

Gender difference update

Girls and boys with autism generally show the same symptoms of ASD overall, but what about different aspects of features? What would happen if you studied girls and boys separately and examined detailed assessments of things like motor skills, repetitive behavior, communication or social interaction? These are where subtle signs of differences between genders is showing up. Girls show a higher age of diagnosis, but that depends on cognitive ability. Also, girls with ASD seem to have superior social interaction skills, which reflects normal gender differences. These differences are magnified over time. A new study also looks at Vitamin D levels during pregnancy and outcome in boys vs. girls…..the results are still unclear but interesting.

https://pubmed.ncbi.nlm.nih.gov/33137209/

https://pubmed.ncbi.nlm.nih.gov/33135392/

https://pubmed.ncbi.nlm.nih.gov/33136459/

Beyond what scientists already know about environmental factors

This week the ASF Podcast explores two ways to better understand the environmental influences in ASD diagnosis: 1. through potential cost savings of avoided cases of ASD due to reduced air pollution and 2. by studying pre-conception exposures going back as far as the grandparents exposure. These two concepts do not prove any one thing, including one environmental factor, causes ASD, however, using these approaches may improve understanding of ASD and allow for legislation that improves many health outcomes in children. Below are the two references:

https://pubmed.ncbi.nlm.nih.gov/32749866/

https://pubmed.ncbi.nlm.nih.gov/32704384/

Age of parents and ASD. It’s complicated.

Questions have loomed around the finding of an increased risk of parents having a child with ASD if they are under 20 or over 35. Of course not every parent who is really young or older will have a child on the spectrum and plenty of those between those ages also have children on the spectrum. Risk factors for ASD are not absolute, they are nuanced and work with other genetic and environmental factors. This week, Kristin Lyall from the AJ Drexel Autism Institute found that those with a strong genetic influence were not as sensitive to factors like parental age. This goes to show, yet again, that it isn’t about ONE risk factor, it’s about dozens working together. And for those 30 year old parents who had a child with autism – see, not every research finding applies to you directly.

https://www.ncbi.nlm.nih.gov/pubmed/32314879

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521130/

Environmental factors: the forgotten stepchild of autism spectrum disorders

When people hear the word “heritability” in mathematical estimates, they automatically think “just genetics”.  That isn’t true, and this week epidemiologist Brian Lee from Drexel talks us through his SpectrumNews viewpoint about what heritability actually is and why there is room for environment.  Also this week, twin studies, which have traditionally used the word heritability to distinguish genetic vs. environmental interactions, are studied in a new light.  This one shows that severity and differences of autism across the spectrum in identical twins are caused by environmental differences – not just genetics.

https://www.ncbi.nlm.nih.gov/pubmed/31853901