OT? Advances in autism understanding

I had double majors in Chemistry and Biology in college but I also took a number of non-science classes for entertainment. (I think they were also required but I thought of them as dessert.)

One of these classes was Psychology 101. One topic in the section on abnormal psychology was autism. The professor showed a video of several autistic boys who showed the same unusual behaviors – repetitive motions, watching phonograph records circle for long periods of time, self-harm (hitting their head against the wall), being emotionally distant from their mothers and other unusual symptoms which were the same for all of them.

According to the professor, autism was caused by emotionally-distant “refrigerator mothers.” I strongly disagreed. I told him that autism is clearly caused by genetics. The problem was that psychologists didn’t know enough about biology to recognize this. (Incidentally, I got an “A” in the course because anyone who can learn organic chemistry can easily memorize psychology – piece of cake.)

Nowadays, of course, it’s clear that autism is, indeed, caused by genetics.

A recent large study ( n = 5,392 autistic people along with 1,972 non-autistic siblings) discovered four classes of autism in which phenotypes of autism are associated with genetic differences. This is a “person-centered” approach which uses combinations of factors instead of focusing on a single factor.

https://www.nature.com/articles/s41588-025-02224-z

As observed clinically, classes differed not only in severity of autism symptoms but also in the degree to which co-occurring cognitive, behavioral and psychiatric concerns factored into their presentation. Factors included limited social communication, restricted and/or repetitive behavior, attention deficit, disruptive behavior, anxiety and/or mood symptoms, developmental delay (DD) and self-injury.

We identified one class that demonstrated high scores (greater difficulties) across core autism categories of social communication and restricted and/or repetitive behaviors compared to other autistic children, as well as disruptive behavior, attention deficit and anxiety, but no reports of developmental delays; this class was named Social/behavioral (n = 1,976).

A second class, Mixed Autism Spectrum Disorder (ASD) with developmental disabilities (DD) (n = 1,002), showed a more nuanced presentation, with some features enriched and some depleted among the restricted and/or repetitive behavior, social communication and self-injury categories and overall strong enrichment of developmental delays compared to both nonautistic siblings and individuals in other classes. The Mixed ASD with DD class was highly enriched in language delay, intellectual disability and motor disorders.

Moderate challenges (n = 1,860) scored fewer difficulties and consistently higher than other autistic children across all seven categories but worse than their non-autistic siblings.

Broadly affected (n = 554) showed significantly higher reported levels of cognitive impairment, lower levels of language ability and much earlier ages at diagnosis.

Differences in phenotypes, co-occurring diagnoses and developmental milestones across the four autism classes correspond to class-specific patterns in genetic signals for common variants. Molecular pathways affected by the patterns of genetic variation observed across phenotypic classes suggested different underlying biological mechanisms. Genes affected by variants in each ASD phenotypic class were associated with unique patterns of gene expression trajectories throughout brain development.
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This is a fascinating study that shows the genetic associations with specific classes of autism.

Early intervention could be more effective if targeted at the specific class that affects a child.

The increasing diagnoses of autism make this an important topic.

The study did not address possible environmental impacts on symptoms that could be interpreted as autistic.
Wendy

https://www.nature.com/articles/s41588-025-02224-z

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You got that right about psychologists/psychology, @WendyBG . I always say, it might rhyme with physiology…but that still doesn’t make it a science!

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Thanks for the article Wendy, I saved it for my files. My thought is that genetics shows who has a predisposition to autism in the same way that it shows who has a predisposition to heart disease as an example. Whether those issues manifest or not and to what degree depends on what circumstances the individual is exposed to.
We know in the case of heart disease that diet, stress level and exercise are all modifying factors. We currently don’t know all the modifying factors with autism but I suspect exposure to substances inflammatory to the CNS that cross the blood brain barrier plays a part. Like you I trained as a doc when the blame was put on the unfortunate parents, mostly the mother. Thank goodness we have moved on from that!

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Yes. And I suspect that video games can promote autism-like behavior in people without a genetic predisposition and may be triggering in people with a genetic predisposition.

Wendy

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Agree.

This is the only environmental association I’ve seen with autism. From a personal/professional observation, didn’t see much autism in the 70s/80s and has increased over the years to be commonplace. Overlaps with the availability of Tylenol. Plus, would fit with a predisposition that needs an environmental exposure to express itself.

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Well, one reason we didn’t seem to see much autism diagnosis in the 1970s and 80s is that the diagnostic criteria were much narrower back then. The expansion since has been a huge help to the families of children on the higher functioning end of the spectrum in getting attention and appropriate consideration/help within the public school system.

An even bigger boost, of course, to the anti vaxxers who still persist in looking at any and every way to link the MMR (and other vaccines) to the condition.

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Here’s an interesting read on the evolution of autism diagnosis. One of many but I don’t feel inclined to read them all (and I have more than a passing interest as my granddaughter is considered “twice exceptional”…which as a broad description could include autism)

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Thanks for the article JLC. Very interesting.
I have two older teachers as my neighbors and they have told me that every year they have a few autistic kids in their classes whereas a couple decades ago that wasn’t the case. And these are the kids who are high enough functioning that they can actually be in a classroom with normal kids. The teachers said that the behavior challenges of these kids can sometimes be triggered in a way that the class is disrupted for awhile but overall it’s manageable. But there are many others who are in special needs classes or who can’t even make it to a classroom at all. I’m in an on-line doc group and I’ve been frankly astounded by how many young physician couples talk about having one or more ASD children. Tylenol possibly being one of the environmental co-factors needs to be in more people’s awareness.

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If you mean that the physicians married and had ASD children, that’s not surprising. It’s been noted for a long time that couples who work in high-tech, marry and have children often have ASD children.

Many people who are attracted to the sciences often have (what used to be called) Asperger’s Syndrome and is now classified as on the autism spectrum. If this is genetically-linked (which evidence supports) the children of two such people could get a double dose.

Albert Einstein’s wife, Mileva Marić, was a Serbian physicist and mathematician. They had two sons who survived to adulthood. The older one became a professor of Hydraulic engineering. The younger one became schizophrenic at age 21.

The brain is a complex organ.
Wendy

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Absolutely. An anecdote to demonstrate (always more persuasive than evidence); When my daughter was in her teens, she became quite friendly with another girl who rode at the same barn. A girl with a very odd affect not inconsistent with high functioning autism…including the straight As at school. Her father just happened to be a colleague of my husband…a well thought of ophthalmologist…and would be described a “a bit Asperger’s-y” like we did back in the 1990s. The younger brother in this family was very low functioning. A big lad with minimal self control and boundary distinction. Was a real worry the the parents as he was not going to get any smaller or easier to manage as he…and they…got older.

Come to think of it, the albatross … in trying to characterise my daughter’s achievements as somehow being due to something other than smartness, hard work, and self motivation … portrayed husband and me as such an odd couple. Dh…according to him…had an MD and 2 PhDs (only one PhD…total underachiever) and me as a self absorbed career driven workaholic (totally the opposite) His pettyfogging lawyer wasn’t interested in evidence to the contrary.