Posted by amichail 12/28/2025
There are perverse consequences in brain chemistry and signalling: flooding a brain deficient in glutamate processing receptors with glutamate may not help, it may overload pathways and cause hindrance, not compensation.
Signs like this may be consequential, or related but not causal, or may simply turn out to be wrong.
IF a small sample effect turns out to be indicative of a larger property, and IF it's shown to be causal and IF remeditation involves boosting blood borne glutamate or precursors is 3 stacked IF.
IF its detectable in a young brain it could be diagnostic.
IF its detectable in a young brain and amenable to gene therapy and IF it's causative then treatment would be useful.
IF excess glutamate is not a problem and dietary supplemented sources cross the blood brain barrier and don't trip over homeostasis then it's possibly worth exploring.
(Not a scientist, not a biologist)
Why not consider the opposite, that the most beneficial quantity of glutamate receptors could be somewhere below the typical amount? If that were true, then we could try to help others reduce their glutamate receptor level to become healthier and more successful (and a little more autistic).
If we found, say, an association between a lower level of neurological characteristic X and concert-level piano skill, then those who aspire to play that instrument at an elite level might try to decrease X. The fact that most of us are rubbish piano players would not be evidence that lower levels of X are harmful, but very much the opposite.
However there are people with severe autism that makes it more or less impossible for them to communicate with other people or live independently. If these people could have their life improved it might make huge difference to them and their families.
Simply put they didn't even touch the keeners, nonverbalists, the piss-in-your-pants, or the perpetual 1 year old autistics. They went after people who previously would be called "Aspergers syndrome".
But everything cognitive seems to be called 'autism spectrum disorder' these days.
Secondly, someone has medical power of attorney over the non-functional autistics. And in reality, they are the ones at most need of (almost passive) study to help them. Us high functioning autistics dont need anywhere near the help.. And we have no way to know an Aspergers and traditional autism are even similar, other than the spectrum brigade keeps adding more and more under 'autism'.
Simply put, guardian says yes to do a single scan a year, and I see no problem with it. More than 1 a year, and we start getting into potential damage. Maybe with some pie-in-the-sky-IRB whatif situation, sure. But 1 scan/yr has no demonstrable damage.
So what I wrote should be read with a "if it is held to be a condition which deserved remediation or avoidance of it's manifestation" attached.
Most medical conditions are couched in this sense, that a deficit or departure from the normal is a problem. In matters of brain chemistry it pays to be more nuanced.
You would not want to boost glutamate. It's the opposite. You want to reduce glutamate and/or increase GABA. The problem is overexcitation, not underexcitation.
The reason the number of receptors might be low in the first place is downregulation from too much glutamate.
Neurotypical does not imply “normal” it only means prevalent - completely different.
Yes, autism sucks _in the contemporary environment_ - we are perhaps better suited for neanderthal / hunter gatherer environment.
However, implying that I should be “cured” for having no interest in NT dynamics and suffer by many of NT byproducts (e.g. noise) puts you up there with Mengle in my book.
If you admit that "autism sucks in the contemporary environment", then, it's pretty clear that there would be people that have it and would want to be rid of it - if only they had that option. Currently, the options they have are "seethe" and "cope" - not a good place to be in. This alone would be enough of reason to look for a cure.
And then there are all the people who lose the "autism lottery" - and end up on assisted living for the rest of their lives. The short straw is really short - you could try an "autism is not a disorder" speech on them, but, not all of them are capable of communicating.
This, too, would be a reason in itself to look for a cure to autism. Unfortunately, what was discovered so far makes an easy solution extremely unlikely.
expected
IMHO, our understanding of autism, specifically, and neural development of the brain, in general, is rudimentary at best. It's too soon to conclude it's incurable.
There is no consensus that autism is like this, but a lot of evidence points that way.
We'd need at least a generational leap in neuroscience to be able to pull off something like that. It's not a "laws of physics prevent you" level of impossible - we just don't have a clue of how would we even begin approaching something like that.
For example, humans clearly have a window for learning their native language. It just happens, and it's nearly magical. But humans can learn non-native languages after that window slams shut. We vary in our ability to do that, but if it matters, most can pick up useful conversational and reading skills.
I agree it's a matter of research. I think we've barely begun to scratch the surface of what's possible.
If people find it easier to learn and apply the workarounds than to learn the thing itself, then, clearly, something prevents them from just learning the thing itself. Behavioral interventions being generally more successful the earlier you do them lines up with that too.
Maybe there are "low hanging fruits", simple interventions that work well that we are yet to discover. But it's not like no one went looking. And the fact that we are yet to find them weights against it.
There seems to be a point of contention amongst the terminology for anybody with autism. Someone with autism might not see themselves as having a disorder. But there are certainly very high needs autistic individuals. Apply a whole spectrum of people as being "developed wrong" and you can start to see ableist language.
I appreciated your metaphor about cars on a highway -- and that there's something wrong with the highway, not the car. I thought it was really simple and clear and I think I got the point you were trying to make. And even if it the highway isn't wrong (it was made for cars after all), we should at least extend it to support many types of transportation.
The ones who weren't so lucky, and got the short straw? They would die without a caretaker to take care of them.
Even among the less severely afflicted: I'm sure there are people who don't mind being autistic, and I'm also sure that there are people who "don't mind being autistic". The difference between the two being: if there somehow was an easy cure, the former wouldn't go for it, but the latter would jump at the possibility. Because their "don't mind" was never anything more than cope. Same as what happened to body positivity in the face of Ozempic.
After digging into it, the hypothesis holds. Most autistic people win this lottery you speak of.
Roughly 25–35% of diagnosed autistic people require substantial, ongoing support (e.g., daily assistance, supervised living, or full-time caregiving).
About 30–40% have co-occurring intellectual disability, which strongly correlates with higher support needs.
Roughly 60–75% do not have intellectual disability. Many in this group: Live independently or semi-independently. Work (often underemployed). Mask heavily and are diagnosed late—or never diagnosed.
Probably not. Because self-selection is doing its work. Out of 10 autistic people you know, ~0 are going to be in the "supervised living" category. They exist - you just don't see them.
Anyway, the core assertion holds. The framing and thinking of autism as a disorder of a brain that developed wrong is out-dated and incorrect. We could also frame the neurotypical brain as wrong for modern society because it evolved to ensure the survival of humans. For example, the typical brain evolved sophisticated fight or flight responses, and efficient pattern matching to quickly respond to physical threats. Both are "wrong" for modern society and civilization because they're rarely necessary for survival and they confound reason and thoughtful analysis.
It's also a fact human intelligence has evolved significantly faster than human physiology. Those people who win the autism lottery, are successful in life, and ultimately have children will contribute to an increase of the proportion of lottery winners in subsequent generations.
Given this new information, better to examine neurological differences rather than focusing on winners and losers, right and wrong.
It's not very helpful to say if someone has been run down by a car that they just have different highway experiences than people who were not run down by cars. Their difference is a significant problem, because they have been run down by a car and it hurts.
More that their brain developed differently and our current highway system is incompatible with that difference.
The highway system can and should change just as we individuals can and should try to change our minds in areas where it makes sense to do so.
My preferred analogy is that all neurodivergent people are playing the game of life at least on hard mode. Some are playing on ultra hard mode. Some are playing on impossible mode.
As it relates to treatment, the goal is to help a person live as close to typical difficulty as possible. Same goal for accommodations extended to the person by society.
So if people discuss the getting run down by car problem level the people who have an "I'm different" problem level feel as if they are being insulted, and if people discuss the "I'm different" problem level the people who care for the people who have been run down by cars feel like... well, insulted would probably be the least of it.
Edit: In retrospect I suppose the “developed wrong” language is insulting to me and the boundary is just beyond the idea of “different”
I suppose then the request is for those people caring for autistic people who are so different life is impossible to live without care to view the concept of “different” as a spectrum too. Not wrong.
I have definite feelings about this exchange on autism, which are being hashed out reasonably without my input. But the Ozempic reference is super interesting. I hope some smart person looks into that particular "correction" vs. "coping" dichotomy at some point in the future.
A timely well executed intervention may make the difference between "needs a caretaker" and a mere "struggles in life". But it's not going to negate all of the damage.
Gene therapies I have little hope for. Maybe something there may help. But the impression I get is that it's less of a "fix biochemical deficits" issue, and more of an "unwire and rewire existing neural circuits" issue. We have no fucking clue on how to do that. And to sidestep that, you'd have to intervene early - maybe as early as "remove genetic predispositions in an embryo".
This is more or less not true. If it doesn't hinder a person in any aspect of their life, they don't fit the DSM-V criteria for a diagnosis.
(Many neurodivergent people aren't hindered by autism because they have some other neurodivergence, but that's a different issue with this sentence)
There is some underlying reality to what autism is, even if we do not have a good understanding of it; and even if turns out to be multiple unrelated things that happen to have similar symptoms.
Of the people with those actual conditions, it seems entirely plausible that some will not be hindered.
The authors of the DSM-V needed to create a diagnostic criteria for a condition that they do not understand, and for which no objective test is known. Further, their objective was designing something useful in a clinical setting. Giving those constraints, saying "if it is not a problem, we don't care about it" is entirely reasonable; despite not being reflective of the underlying reality.
To a first approximation, the DSM is about what a majority thinks is wrong. Sometimes this is pretty close to universal. Sometimes it isn't: https://en.wikipedia.org/wiki/Homosexuality_in_the_DSM
This study suggests that there are several different things called "autism". That's because "autism" as a term is not about some underlying reality, but a bucket that a bunch of people get tossed when some medical professionals see them as similar. And they come to the attention of those medical professionals because those people either say they have a problem or are called a problem by others.
But a problem with a person is always about a person in a context. Blue-eyed people are hindered by their eyes in bright light. Do we call that a genetic disease and look for cures? Not here, because there are enough "normal" people with blue eyes. But if it was just 1 in 20,000 people with blue eyes, it'd surely be treated as a disease.
Or we could imagine a "Height Deficiency Syndrome" characterized by inability to reach the top shelves in a normal house. With an effort, we could surely cure this impactful genetic problem through early application of hormones and the use of new CRISPR-related technologies. Or we could look at it as normal human variation which only "hinders" people because of how our society is set up to cater to "normal" people.
But we thankfully now have a term for that sort of nonsense: medicalization of deviance.
Society punishes us severely for not being able to see the difference between red and green, to use that metaphor. And they seem to expect that if they punished us just a little harder, we would suddenly become normal. Thats the big problem. Non conforming behavior is always treated as a crime or offense on some level, but we cannot conform, and therefore must adjust to a life of endless punishment doled out by both authorities and peers.
Its quite difficult to go through life that way without developing a negative self image. This goes for people with autism, adhd and other types of neurodivergence.
And then you meet the next person, who has not yet tortured and broken you, so they again do not believe that you "don't have the intel", and you get to go through it all over again.
The worst part is when you start believing for yourself that they're right, that you're holding back, and that it's all your fault for not giving them what they want, just for the life of you you can't figure out how.
Getting certainty about my condition did so much to heal me.
1. "Normal" people with a level of glutamate receptors at 10, say, on a scale I'm inventing for this example
2. "Autistic" (according to the DSM) people with a level of, say, 5, who are hindered by the effects of being at this level
3. "A little bit autistic" people at a level of, say, 8, who aren't hindered and don't meet the DSM criteria, but in fact actually benefit from the effects of being at this level
Some "normals" might then want to inhibit their glutamate receptors somewhat to get the benefits of being at an 8 or a 9 on my made-up scale.
Just like with ADHD it's likely that medication will at best have limited effectiveness and many side effects.
"Deficits are sufficiently severe to cause impairment in personal, family, social, educational, occupational or other important areas of functioning..."
> A case of HIV infection is defined as an individual with HIV infection irrespective of clinical stage including severe or stage 4 clinical disease (also known as AIDS) confirmed by laboratory criteria according to country definitions and requirements.
and rarely they may never have met these criteria. This is HN, so a computer analogy might be more helpful: ask a non-technical friend to read through some of the POSIX.1-2024 spec, then ask them to explain the signal handling, or the openat error codes. They will totally misunderstand it, because the POSIX specs are not actually clear: their purpose is to jog the memory of the expert reader, and describe the details they might have forgotten, not to provide a complete and accurate description suitable for teaching.
(Edit: pointless confrontational passage excised. Thanks for the criticism.)
> Are you a trained psychologist?
seems a bit confrontational, unless you yourself are a trained psychologist, in which case it would seem fitting to volunteer those credentials along with this challenge.
So the definition is perfectly correct, assuming you know what "clinical stages" there are.
I think that's all an aside, though, if not the ICD (as suggested by another poster) or the DSM definition initially used, which definition is correct?
OP, I think, is clearly harkening back to a previous post on HN (article at: https://www.psychiatrymargins.com/p/autisms-confusing-cousin...) by a professional discussing that the public often misunderstands and ignores key aspects of the definition. This seems rather a bit like you pointing out laypeople might read and not understand what they got out of the POSIX.1-2024 spec. Except it seems you're suggesting instead that the layperson understanding is correct.
Mu. If it was confirmed, but not "confirmed by laboratory criteria according to country definitions and requirements", then they do not meet the diagnostic criteria (interpreted literally). Suppose, for instance, that there was a procedural error that might have messed up the diagnosis (so is forbidden by regulation), but in this case didn't mess up the diagnosis.
I can produce as many of these literally-correct, deliberate misinterpretations as you like. They have no bearing on actual medical practice.
> which definition is correct?
Which definition of "carbon atom" is correct? Our definitions have, for 200 years, been sufficient to distinguish "carbon atom" from "not carbon atom", but those definitions have changed significantly in that time. Autism is that category into which autistic people fall, and into which allistic people do not fall, which is distinguished from several other categories with which it is often confused. (The ICD-11 spends way more words on distinguishing autism from OCD, Tourette's, schizophrenia, etc than on defining it directly.)
Now, needless to say, this is not how anyone actually thinks about psychiatric or psychological issues in practice, especially with conditions such as autism, and just highlights the relative absurdity of some of the diagnostic metrics, practices and definitions.
What we tend to do is tie the diagnosis of autism to the individual identity and assume that it is a consistent category and applicative diagnosis that stays with a person over time because it is biological. We know, of course, that this is despite not having any working biological test for it, and diagnosing it via environmental and behavioural contexts. And don't even get me started on tying in diagnosis of aspergers/autistic individuals with broadly differing abilities and performance metrics on a range of metrics under the one condition such that the non-verbals and low-functioning side of neurotypicals get lumped in with the high iq and hyper-verbal high-functioning aspergers as having the same related condition even though neurotypicals are closer to the non-verbals and low-iqs on the same metrics and scores.
The entire field and classification system, along with the popular way of thinking about the condition is, if i might editorialise, an absolute mess.
A similar example could be made of someone with gluten intolerance. If they do not eat foods that contain gluten they are still gluten intolerant. They are however still disabled by needing to stay in that situation.
Firstly a fish without legs objectively does not have legs, but we do not necessarily call it disabled, even though it clearly lacks a facility.
Secondly, the autism spectrum disorders are, as I previously mentioned, not obviously just about deficits of behaviours or functions but also can take in extended and exceptional abilities in some areas and greater sensitivities rather than deficits or lack of an ability, so it is not clear that the entire diagnosis can be defined by deficits or lacking things. The high functioning and Asperger's type diagnosis is not about a universal deficit diagnosis and we do not generally call neuro-typical humans disabled because they lack prodigious activity or interest in math, language, or other subjects, even though that can also objectively be measured and called a deficit.
To get an Asperger's diagnosis under the DSM-IV you needed some amount of impairment. "Disorder" is in the title of the DSM, if something isn't conceptualized as a disorder it isn't in there.
https://www.kennedykrieger.org/stories/interactive-autism-ne...
The "broader autistic phenotype"- that is, related traits but without impairment- exists but it is not a diagnosis.
That would be a bit weird though...
EDIT: Neurodivergent is very much a broader category. What I meant would be weird is to state the obvious... Very much sounded like they were trying to say some people with autism may not want to get "cured" but using the wrong words
The only possible exception I can think of is synaesthesia.
That can certainly be a syndrome, but the official DSM definition of autism is not based on those criteria.
Clinical autism tends to be much harsher in its presentation.
Adults have been socialised to mask the more problematic behaviours, and they can also be unaware that what they're doing is masking: they can believe that everyone struggles like that.
Why do we care so much about objective evidence? Because of prohibition. Prescribing stimulants isn't illegal because it is difficult to diagnose ADHD. It's difficult to diagnose ADHD for the very same reason it's illegal to prescribe stimulants: our society values prohibition of drugs over actual healthcare. An ADHD diagnosis implies a compromise of prohibition, so our society has structured the means to that diagnosis accordingly.
Experts in the field estimate a very high incidence of undiagnosed ADHD in adults. During the height of the COVID-19 epidemic, telehealth services were made significantly more available, which lead to a huge spike in adult ADHD diagnoses. Instead of reacting to that by making healthcare more ADHD accessible, our society backslid; lamenting telehealth providers as "pill mills", and generating a medication shortage out of thin air.
That may be true for ADHD, but autism diagnoses don't "unlock" any particularly sought-after prescription medication, so I don't think that can be the whole story. In kids, diagnoses do unlock accommodations in schools, but not so much for adults.
You're confusing autism itself with Autism Spectrum Disorder. Autism Spectrum Disorder indeed has to do with difficulties ("deficits" / "impairment"). Autism itself on the other paw is a physical, quantifiable difference in neural architecture. Autistic people think and work differently, whether they have been diagnosed with Autism Spectrum Disorder or not.
It's also worth noting that autism is not the only neurodivergence, it's just the most widely known one (IIRC).
For reference, my copy of the DSM-5 states the following diagnostic criteria for Autism Spectrum Disorder: (sub-items elided)
> A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history (examples are illustrative, not exhaustive; see text): [...]
> B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history (examples are illustrative, not exhaustive; see text): [...]
> Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life).
> D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.
> E. These disturbances are not better explained by intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level.
https://www.verywellhealth.com/broad-autism-phenotype-117279...
The autism in this study is ASD. This study doesn't have that much to say about people who don't qualify for a diagnosis, since they would not have qualified to take part in it.
But yes, if you are saying ASD (and not autism itself, as you quoted from the article) is by definition a hindrance, I would be inclined to agree with you, for the reasons you've outlined.
BAP, I think, comes from heritability studies of people who are related to diagnosed people but do not themselves qualify as autistic, they are more likely to have traits associated with ASD despite not being diagnosable.
The only people who take the DSM seriously are insurance agents and charlatans.
Neurons specifically increase / decrease receptor density in response to environmental factors, eg: use of SSRI's. Any excess of neurotransmitter would likely lead to reduction in receptor density as part of the response. So the story can be as much about an excess of neurotransmitter as it is about depletion of the receptor.
Perhaps the main story here is they can use EEGs as a proxy for measuring this effect so they don't need to put people through PET scans to do wider studies.
> We want to start creating a developmental story and start understanding whether the things that we’re seeing are the root of autism or a neurological consequence of having had autism your whole life
Wish I could read the paper.
doi: 10.1016/j.bbi.2015.05.009
But here there’s a basic design flaw. This is a study of 16 ASD cases and 16 neurotypical controls. Small sample sizes like this require careful matching. The problem: the autistic subjects are 100% White but controls are 37.5% White. That imbalance can’t be waved away with statistics or Jedi mind tricks. Recruiting matched neurotypicals would have been straightforward.
One other issue is high heterogeneity within the two groups. In their Figure 1 (sorry behind a paywall), 4 - 6 of the autistic individuals have low mGlu5 levels across all regions. Two or three neurotypicals have high levels. Are these distributions actually normal, or are subgroups driving effects? It would help to know whether the participants’ GRM5 genotypes were informative wrt these subgroups. They weren’t checked.
[1] "The findings support the idea that an imbalance of excitatory and inhibitory signals in the brain could be contributing to traits associated with autism, the researchers say." https://medicine.yale.edu/news-article/molecular-difference-...
[2] "Converging evidence from diverse studies suggests that atypical brain connectivity in autism affects in distinct ways short- and long-range cortical pathways, disrupting neural communication and the balance of excitation and inhibition." https://doi.org/10.3389/fnhum.2013.00609
I don't know much about the biochemistry here, I assume this is not something like GABA that can be directly supplemented. But maybe there are precursor nutritional and supplemental substances that can help these people upregulate how much of the glutamate molecule in question the body can produce.
> Now, a new study in The American Journal of Psychiatry has found that brains of autistic people have fewer of a specific kind of receptor for glutamate, the most common excitatory neurotransmitter in the brain. The reduced availability of these receptors may be associated with various characteristics linked to autism.
Reduce receptors. This might suggest a _developmental_ or genetic link. Think of this more like "height" or a particular "facial feature" of a person.
> Reduce receptors. This might suggest a _developmental_ or genetic link. Think of this more like "height" or a particular "facial feature" of a person.
No. This isn't how it works at all. Receptor counts are extremely plastic, able to change within a weeks and in some cases hours. This is how you get drug tolerance.
Supplimentation would not rewrite SHANK3.
You can go to the dentist and get your teeth aligned, but there's a very good chance your children have similar issues.
For now, your best options are ESDM, occupational therapy, modified CBT, ABA, or neurofeedback, depending on your circumstances and presentation. Except for neurofeedback, these are behavioral approaches, so the architectural and neural activity variations aren't directly addressed.
To me it's kind of the biggest red flag here, if it's really about receptors then autism should be far more plastic than it is currently defined to be (which is kind of silly since at the moment any sign of plasticity puts you outside one of the hard criteria for an autism diagnosis - so almost definitionally, it can't be the answer).
So we might be able to make all the non-autistic people autistic? What would the world be like if everyone was mildly autistic?
My impression is this article and research that generalizes across the entire spectrum is not very useful.
It's somewhat comparable to using a handheld magnifying glass on petri dishes and making broad claims about virus morphology. EEG is great, but I'm not sure I buy the methodology in this case. You need a huge N and much better experimental design and absolutely zero hype unless or until you show results with scientific rigor.
This sort of clickbait almost makes me view this type of research as a flavor of pseudo-science. The framing is misleading at best, but the full throated embrace of the clickbait and hype machine is awful.
It's funding bait, narrative manipulation, etc, and it'll either be part of something replicated and justified with much better experiments, or it'll just fade away into oblivion, with no repercussions for any involved should the outcome not actually benefit anyone or anything. There's not even a negative incentive, mGlu5 and "imbalance" claims have been made for decades, and they keep circling the questions but don't ever seem to actually "do" real science.