Autism mutations drive neurodevelopmental pathology • Hacker News Board

Re: Autism mutations drive neurodevelopmental pathology

#131

Post by inigyou » Fri, Aug 28, 2026, 4:36 AM UTC

roughly wrote: post #59

SubiculumCode wrote: post #25

Earlier quoted context omitted.

A lot of the behaviors by which autism is diagnosed (social communication, repetitive behaviors and restricted interests) are fairly high-level behaviors, dependent on a lot of cognitive/neural machinery beneath it. There is an idea out there that convergent behaviors that allow consistent diagnosis depends on this, as the resulting behaviors might results from differences in many different underlying processes, but…

Ok, that makes sense - so ASD is basically that we’ve noticed some prototypical behaviors, which is where the grouping comes from, but it’s possible what we’re seeing is sort of the “carcinization” of mental operating modes - many different pathways into the same output point, which is why the genetic search has been so difficult - that right enough for a non-scientist? What I know of the brain is that it’s basically…

Notice how the word "syndrome" as in the older term "Asperger's syndrome" describes a group of symptoms, rather than a cause.

Re: Autism mutations drive neurodevelopmental pathology

#132

Post by inigyou » Fri, Aug 28, 2026, 4:37 AM UTC

EQFitzgerald wrote: post #129

sublinear wrote: post #36

Earlier quoted context omitted.

Is high-level behavior the only criteria for diagnosis? I think the majority of the public would like to better understand how we came into this position. There's nothing wrong with the topic of autism as research, but it's been a political football for so long that there are many reasonable doubts about methodology, diagnosis, and relevance to everyday healthcare. I understand there may be complications with some pa…

On the contrary, autistic people tend to be way too mature for their age, often visibly so. (it used to be called the "little professor syndrome") It seems to me that's what they actually found - the genes accelerate maturation. Maybe it's just the neoteny fetish of the modern society that makes it feel like a disorder.

Maybe but in that case they are then less mature in other ways due to not having the proper formative experiences. And what's wrong with neoteny?

Re: Autism mutations drive neurodevelopmental pathology

#133

Post by inigyou » Fri, Aug 28, 2026, 4:42 AM UTC

Alex3917 wrote: post #23

roughly wrote: post #12

Earlier quoted context omitted.

Out of curiosity, what leads us to treat ASD as an actual single disorder, as opposed to a billion different individual neurological profiles? I'd expect one of the things that makes this difficult, too, is that there's a missing component of the "machine" - the genetics affect the pathways, which affect (maybe?) things like signal propagation or network regulation in the brain, but the actual effect of that is on th…

> what leads us to treat ASD as an actual single disorder, as opposed to a billion different individual neurological profiles? We already do treat it as the latter. The medical definition of autism is basically just any neurodevelopmental disorder that isn’t ADHD.

This hypothesis runs into the slight problem that autism and ADHD are highly co-occurring.

Re: Autism mutations drive neurodevelopmental pathology

#134

Post by inigyou » Fri, Aug 28, 2026, 4:43 AM UTC

nerdralph wrote: post #115

SubiculumCode wrote: post #6

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…

I'm an aspie, and think my "version" of ASD has a large epigenetic component. I think social emotions that develop through childhood and adolescence happen through epigenetic changes that enable and disable sets of genetic material (not necessarily just genes) as the person develops. I think the physical changes that happen with puberty must involve timed epigenetic changes. I think the same thing happens with emotio…

If you don't feel lust, why did you have a girlfriend?

Re: Autism mutations drive neurodevelopmental pathology

#135

Post by inigyou » Fri, Aug 28, 2026, 4:44 AM UTC

XCSme wrote: post #27

SubiculumCode wrote: post #6

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…

As a potential autist, I think everyone is autistic in one way or another (which would make everyone neuroytpical, lol). In the end, maybe we are just all unique individuals with our character sliders set in various forms.

Bimodal distributions exist

Re: Autism mutations drive neurodevelopmental pathology

#136

Post by inigyou » Fri, Aug 28, 2026, 4:46 AM UTC

XCSme wrote: post #102

autoexec wrote: post #64

Earlier quoted context omitted.

> But different autistic people struggle with different things, in different ways. Different asthmatic people struggle with different things, in different ways too, but it's useful to have a general diagnosis umbrella to cover those who have asthma even though symptoms and effective treatments may vary. Work is ongoing to get better defined categories for autistic people, but for now at least we've got a category for…

The problem is that the set of problems is very broadly defined, changes over time, varies from person to person, it's often impossible to obiectively test. Can't it be that a neurotypical person is bothered by some autistic triggers? Would that make them neurodivergent? How many of those triggers do you need to have to be under that umbrella? 1? 5? 20? It is indeed called a spectrum, and I think it gets so fuzzy at…

It's a bimodal distribution. There are people with few of these traits lightly, and people with many or with a few severe ones. Not so many in between. This already makes it an interesting line to draw.

Re: Autism mutations drive neurodevelopmental pathology

#137

Post by inigyou » Fri, Aug 28, 2026, 4:47 AM UTC

hoppp wrote: post #54

XCSme wrote: post #50

Earlier quoted context omitted.

I said that if everyone is neurodivergent, then no one is. Same with IQ, if everyone is 150IQ, then everyone is still 100IQ, as per the definition, so "normal". Divergence can only be mentioned when talking a base value to diverge from. What if neurotypicals are actually the neurodivergent ones?

Typicals are the neurotype that reproduces fastest, that's it.

What about psychopaths?

Re: Autism mutations drive neurodevelopmental pathology

#138

Post by inigyou » Fri, Aug 28, 2026, 4:48 AM UTC

DoctorOetker wrote: post #103

SubiculumCode wrote: post #37

Earlier quoted context omitted.

First, and foremost, the rise in autism rates is due to more sensitive instruments, a broadening of some inclusion criteria between DSM 4 and 5, more awareness of autism, less stigma associated with autism, services attached to autism diagnosis. I believe current research suggests these don't account for all the rise, but does account for most of it. If I were to include additional biological possibilities, I'd inclu…

> If I were to include additional biological possibilities, I'd include: a) birth control -> waiting to have children until a later age, more de novo mutations due to age. Surely it should be easy to collect the data to plot such a hypothesis: incidence rate vs age of father and vs age of mother at conception, and at birth.

Be careful of reverse causation. Being autistic makes you more likely to have children later (if at all) and we know it's at least partially heritable.

Re: Autism mutations drive neurodevelopmental pathology

#139

Post by inigyou » Fri, Aug 28, 2026, 4:49 AM UTC

coldtea wrote: post #71

john_strinlai wrote: post #35

Earlier quoted context omitted.

> Genetics does not explain steep raise in last a few decades. as we built better telescopes, we found more stars

Quick and cheap explanation many use, but not the case. Severe autism is also on the rise, and that doesn't need special telescopes, it's just evident.

Well we used to just let those people die. You know how the medieval family had like 15 children and 4 survived to adulthood? Some of those 11 were severely autistic.

Re: Autism mutations drive neurodevelopmental pathology

#140

Post by inigyou » Fri, Aug 28, 2026, 4:52 AM UTC

klipt wrote: post #33

AndrewDucker wrote: post #7

Earlier quoted context omitted.

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.

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...

that's easy right? you just gotta ssik a ecnirp.