10 ms·

Autism mutations drive neurodevelopmental pathology

111 points by slantedview 21d ago

kayo_20211030 21d ago
I'm interested - for reasons. Does anyone have a sense of what this study means in a practical or actionable sense? In toto, the conclusion of the paper: > Together, these findings define a dual-layered model of molecular convergence in ASD: convergence through shared interaction networks in the wild-type state and convergence through recurrent functional consequences of interaction rewiring in the mutant state. More broadly, this work establishes a scalable framework for systematic interrogation of the autism proteome, enables prioritization of druggable protein interfaces, and provides a rational foundation for precision therapeutic strategies aimed at restoring neurodevelopmental trajectories. I have no grounding here. Does anyone want to have a go at teasing the meaning out?
- rickydroll 21d ago
  I interpret it as they think they can find treatments that will course-correct the development of a child, but they're not saying anything about fixing something that's already broken.
  - kelseyfrog 21d ago
    Brave to say on one of the most autistic web forums that autistic people have something that's broken :|
    - krapp 21d ago
      This isn't /g/ what are you talking about?
    - djaro 21d ago
      I mean, it's classified as a disability for a good reason. I would guess that even if this platform has more autistic people due to being tech focused, autistic tech nerds and programmers are on the extreme end of high-functioning. Many low-functioning autistic people will never be able to have a job or live by themselves. This is the same issue as high-functioning ADHD'ers saying "ADHD is my superpower", meanwhile people with severe ADHD do significantly worse than the general population in basically any metric, up to having a lower life expectancy. This isnt to say its morally bad, theres nothing wrong with being autistic or having ADHD, but it is a disability. Just like someone who's deaf can live a totally happy life but still be disabled because they are not able to hear, someone with autism is disabled because they are not able to process social cues at the same speed, even if they are a great person and have a good life.
      - seanhandley 21d ago
        It depends, and that’s the point. It’s such a wide concept. Essentially it boils down to how a brain processes sensory information and at what point it becomes overwhelmed. We all have tolerances set at different gauges. It’s a disability if it’s at odds with the environment a person finds themselves in.
      - forestrywat 21d ago
        "Have a disability" and "broken" are not synonyms. There's no judgement or moralizing in having a disability. Autism and ADHD like you mentioned are disabilities. But the people who have them are not broken. Having a disability means some part of your life is more difficult. But that's very very different from you as a person are broken. For example, if you can fix the environment and the person can now function equally to someone without a disability, then maybe it's the environment that's broken. If you can fix the social expectation and suddenly the person can function equally, then maybe the society is broken. Even if you cannot accommodate the person's needs, insinuating they are broken is not a great framing -- it creates a sense of pity rather than constructively looking at means to support them.
        nick__m 21d ago
        What else but pity should I feel toward non verbal autistic people?
        kelseyfrog 20d ago
        Compassion?
        forestrywat 20d ago
        Love? Affection? Friendship? Camaraderie? Care? All the stuff you feel towards any other human?
        hoppp 21d ago
        What is strange about the disability is when neurotypicals attack autists. It takes less then 1 second for the negative bias to trigger. If you see a person without legs, do you tell him he is a piece of shit because he can't run? So why harass autistic people?
    - SubiculumCode 21d ago
      Autism is a spectrum. Neurodiversity within and outside of autism is both intrinsically valuable and extrinsically valuable to society. However, not all phenotypes of autism should be viewed as neurodiversity, but as harmful. There is only so much that society can do to make severe intellectual impairments less disabling without identifying a cure for the intellectual impairment. The debate between medical versus disability models, neurodiversity versus pathology, inevitably gets pushed by those that want to classify everything into clean essentialist boxes, but that, I do not believe, is a helpful way to view the world. Not every condition is a pathology, nor is every condition benign if only society would do more to make it less disabling.
  - Muromec 21d ago
    I for once enjoy the glitches in my signal mixing module, don't want nothing to fix there.
    - creaturemachine 21d ago
      It's the normies that are missing out.
  - forestrywat 21d ago
    What do you mean "broken"? Autistic folks are not broken.
    - raducu 21d ago
      Nobody said they were, but broken in terms of neurotypical circuitry, yes
    - djaro 21d ago
      Autism is a disability. The function of the brain to normally process social cues is broken. In the same way someone who is blind has broken vision, someone in a wheelchair has broken legs, and someone with ADHD has broken executive function. This isnt a moral judgement, theres nothing wrong with being disabled, but it remaims a disability that many people struggle due to.
      - hoppp 21d ago
        The disability exists when compared to neurotypicals but does not necessarily exist when compared to other autists. As a comparison, if you put a bonobo with chimps the bonobo will be severely disabled socially, but it won't be when compared to other bonobos. The fact that autists can communicate with each other does not fit typical models of disability. A blind person should be blind to another blind person.
      - SubiculumCode 20d ago
        There is interesting evidence that autism-autism social interactions are fairly vibrant. Everything is a bit more complicated than simple answers, no matter which way you swing.
      - forestrywat 20d ago
        You've agreed with what I said. Nothing here is counter to or in opposition to my point. The person has a disability. Part of the person may be broken, but the person isn't broken. I'm autistic. My sensory processing wiring is different and arguably broken. But I am not. I'm disabled. I can overcome the broken parts that result in my disability with support.
- slantedview 21d ago
  There's a CNN article that has some expert quotes for context, but isn't quite as in depth as the study itself: https://archive.ph/yBiM8 https://archive.ph/yBiM8
- AndrewDucker 21d ago
  Nothing yet. This is incredibly preliminary, with lots of this being tested in frogs. It hopefully gives hints which will be tested,better understood, and show actual mechanisms in humans. But probably not for years.
  - klipt 21d ago
    Dr: I have good news and bad news Patient: What's the good news? Dr: We have a two step treatment to improve your social-emotional life. Patient: What's the bad news? Dr: The first step is, we have to turn you into a frog...
    - inigyou 20d ago
      that's easy right? you just gotta ssik a ecnirp.
- randomImmigrant 21d ago
  Here’s how I’m thinking about it (still digging into the details): across genomics, it’s become clear few traits have clear traceability to a few loci in the genome. Instead, evidence has been growing that epistasis, the nonlinear interaction between genes and other genomic regions, predominates in explanations of most phenotypes. What this paper does is show where upstream of the genome various combinations of mutations can interact to cause damage during development, thus leading to the phenotype. Rather than correcting a particular mutation, or targeting drugs to their protein products, we may find downstream protein-protein interactions that are strong drivers of the phenotype, and hopefully find ways to prevent/reverse these effects.
SubiculumCode 21d ago
autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are associated with autism, some strongly, most very weakly. Many have suspected that this plethora of genetic variants might converge onto a smaller set of biological pathways affecting neurodevelopment in ways that results in an autism phenotype or phenotypes. This has been our hope, because the alternative scares the hell out of a scientist. The saying goes that if you met one person with autism, you've met one person with autism...meaning there is a ton of heterogeneity within the autism spectrum, even if a certain set of core autism symptoms are displayed. So there was a existential crisis that there is no "autism", just a billion autisms, where your sample size is always N=1. By demonstrating evidence that many variants converge on the same biological pathways, there is hope that understanding autism is tractable.
- gignico 21d ago
  I thought the US government had just decided that the cause of autism was vaccines </sarcasm>
  - emptybits 21d ago
    No need for your </sarcasm> tag. The United States makes repeated claims linking childhood vaccines to autism. https://www.factcheck.org/2026/08/trump-and-rfk-jr-repeat-false-and-misleading-vaccine-claims/ https://www.factcheck.org/2026/08/trump-and-rfk-jr-repeat-fa...
    - maddie0 21d ago
      Come now! It is clear that the sarcasm indicator wasn't suggesting that the government didn't really announce that. The sarcasm was in the invocation of governmental authority, which is thereby implied to be ill-founded and not worth listening to.
anotherevan 20d ago
“In an ideal world the scientist should find a method to prevent the most severe forms of autism but allow the milder forms to survive. After all, the really social people did not invent the first stone spear. It was probably invented by an Aspie who chipped away at rocks while the other people socialized around the campfire. Without autism traits we might still be living in caves.” http://www.azquotes.com/quote/362838 http://www.azquotes.com/quote/362838

111 points by slantedview 21d ago

kayo_20211030 21d ago

I'm interested - for reasons. Does anyone have a sense of what this study means in a practical or actionable sense? In toto, the conclusion of the paper: > Together, these findings define a dual-layered model of molecular convergence in ASD: convergence through shared interaction networks in the wild-type state and convergence through recurrent functional consequences of interaction rewiring in the mutant state. More broadly, this work establishes a scalable framework for systematic interrogation of the autism proteome, enables prioritization of druggable protein interfaces, and provides a rational foundation for precision therapeutic strategies aimed at restoring neurodevelopmental trajectories. I have no grounding here. Does anyone want to have a go at teasing the meaning out?

rickydroll 21d ago
I interpret it as they think they can find treatments that will course-correct the development of a child, but they're not saying anything about fixing something that's already broken.
- kelseyfrog 21d ago
  Brave to say on one of the most autistic web forums that autistic people have something that's broken :|
  - krapp 21d ago
    This isn't /g/ what are you talking about?
  - djaro 21d ago
    I mean, it's classified as a disability for a good reason. I would guess that even if this platform has more autistic people due to being tech focused, autistic tech nerds and programmers are on the extreme end of high-functioning. Many low-functioning autistic people will never be able to have a job or live by themselves. This is the same issue as high-functioning ADHD'ers saying "ADHD is my superpower", meanwhile people with severe ADHD do significantly worse than the general population in basically any metric, up to having a lower life expectancy. This isnt to say its morally bad, theres nothing wrong with being autistic or having ADHD, but it is a disability. Just like someone who's deaf can live a totally happy life but still be disabled because they are not able to hear, someone with autism is disabled because they are not able to process social cues at the same speed, even if they are a great person and have a good life.
    - seanhandley 21d ago
      It depends, and that’s the point. It’s such a wide concept. Essentially it boils down to how a brain processes sensory information and at what point it becomes overwhelmed. We all have tolerances set at different gauges. It’s a disability if it’s at odds with the environment a person finds themselves in.
    - forestrywat 21d ago
      "Have a disability" and "broken" are not synonyms. There's no judgement or moralizing in having a disability. Autism and ADHD like you mentioned are disabilities. But the people who have them are not broken. Having a disability means some part of your life is more difficult. But that's very very different from you as a person are broken. For example, if you can fix the environment and the person can now function equally to someone without a disability, then maybe it's the environment that's broken. If you can fix the social expectation and suddenly the person can function equally, then maybe the society is broken. Even if you cannot accommodate the person's needs, insinuating they are broken is not a great framing -- it creates a sense of pity rather than constructively looking at means to support them.
      - nick__m 21d ago
        What else but pity should I feel toward non verbal autistic people?
        kelseyfrog 20d ago
        Compassion?
        forestrywat 20d ago
        Love? Affection? Friendship? Camaraderie? Care? All the stuff you feel towards any other human?
      - hoppp 21d ago
        What is strange about the disability is when neurotypicals attack autists. It takes less then 1 second for the negative bias to trigger. If you see a person without legs, do you tell him he is a piece of shit because he can't run? So why harass autistic people?
  - SubiculumCode 21d ago
    Autism is a spectrum. Neurodiversity within and outside of autism is both intrinsically valuable and extrinsically valuable to society. However, not all phenotypes of autism should be viewed as neurodiversity, but as harmful. There is only so much that society can do to make severe intellectual impairments less disabling without identifying a cure for the intellectual impairment. The debate between medical versus disability models, neurodiversity versus pathology, inevitably gets pushed by those that want to classify everything into clean essentialist boxes, but that, I do not believe, is a helpful way to view the world. Not every condition is a pathology, nor is every condition benign if only society would do more to make it less disabling.
- Muromec 21d ago
  I for once enjoy the glitches in my signal mixing module, don't want nothing to fix there.
  - creaturemachine 21d ago
    It's the normies that are missing out.
- forestrywat 21d ago
  What do you mean "broken"? Autistic folks are not broken.
  - raducu 21d ago
    Nobody said they were, but broken in terms of neurotypical circuitry, yes
  - djaro 21d ago
    Autism is a disability. The function of the brain to normally process social cues is broken. In the same way someone who is blind has broken vision, someone in a wheelchair has broken legs, and someone with ADHD has broken executive function. This isnt a moral judgement, theres nothing wrong with being disabled, but it remaims a disability that many people struggle due to.
    - hoppp 21d ago
      The disability exists when compared to neurotypicals but does not necessarily exist when compared to other autists. As a comparison, if you put a bonobo with chimps the bonobo will be severely disabled socially, but it won't be when compared to other bonobos. The fact that autists can communicate with each other does not fit typical models of disability. A blind person should be blind to another blind person.
    - SubiculumCode 20d ago
      There is interesting evidence that autism-autism social interactions are fairly vibrant. Everything is a bit more complicated than simple answers, no matter which way you swing.
    - forestrywat 20d ago
      You've agreed with what I said. Nothing here is counter to or in opposition to my point. The person has a disability. Part of the person may be broken, but the person isn't broken. I'm autistic. My sensory processing wiring is different and arguably broken. But I am not. I'm disabled. I can overcome the broken parts that result in my disability with support.
slantedview 21d ago
There's a CNN article that has some expert quotes for context, but isn't quite as in depth as the study itself: https://archive.ph/yBiM8 https://archive.ph/yBiM8
AndrewDucker 21d ago
Nothing yet. This is incredibly preliminary, with lots of this being tested in frogs. It hopefully gives hints which will be tested,better understood, and show actual mechanisms in humans. But probably not for years.
- klipt 21d ago
  Dr: I have good news and bad news Patient: What's the good news? Dr: We have a two step treatment to improve your social-emotional life. Patient: What's the bad news? Dr: The first step is, we have to turn you into a frog...
  - inigyou 20d ago
    that's easy right? you just gotta ssik a ecnirp.
randomImmigrant 21d ago
Here’s how I’m thinking about it (still digging into the details): across genomics, it’s become clear few traits have clear traceability to a few loci in the genome. Instead, evidence has been growing that epistasis, the nonlinear interaction between genes and other genomic regions, predominates in explanations of most phenotypes. What this paper does is show where upstream of the genome various combinations of mutations can interact to cause damage during development, thus leading to the phenotype. Rather than correcting a particular mutation, or targeting drugs to their protein products, we may find downstream protein-protein interactions that are strong drivers of the phenotype, and hopefully find ways to prevent/reverse these effects.

SubiculumCode 21d ago

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are associated with autism, some strongly, most very weakly. Many have suspected that this plethora of genetic variants might converge onto a smaller set of biological pathways affecting neurodevelopment in ways that results in an autism phenotype or phenotypes. This has been our hope, because the alternative scares the hell out of a scientist. The saying goes that if you met one person with autism, you've met one person with autism...meaning there is a ton of heterogeneity within the autism spectrum, even if a certain set of core autism symptoms are displayed. So there was a existential crisis that there is no "autism", just a billion autisms, where your sample size is always N=1. By demonstrating evidence that many variants converge on the same biological pathways, there is hope that understanding autism is tractable.

gignico 21d ago
I thought the US government had just decided that the cause of autism was vaccines </sarcasm>
- emptybits 21d ago
  No need for your </sarcasm> tag. The United States makes repeated claims linking childhood vaccines to autism. https://www.factcheck.org/2026/08/trump-and-rfk-jr-repeat-false-and-misleading-vaccine-claims/ https://www.factcheck.org/2026/08/trump-and-rfk-jr-repeat-fa...
  - maddie0 21d ago
    Come now! It is clear that the sarcasm indicator wasn't suggesting that the government didn't really announce that. The sarcasm was in the invocation of governmental authority, which is thereby implied to be ill-founded and not worth listening to.

anotherevan 20d ago

“In an ideal world the scientist should find a method to prevent the most severe forms of autism but allow the milder forms to survive. After all, the really social people did not invent the first stone spear. It was probably invented by an Aspie who chipped away at rocks while the other people socialized around the campfire. Without autism traits we might still be living in caves.” http://www.azquotes.com/quote/362838 http://www.azquotes.com/quote/362838