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)
Something in the brain development has gone off course - and by the time you see the early symptoms, it has been off course for a while already. Early interventions help considerably, but you might have to intervene extremely early, before any clinical symptoms show, to prevent it. Even if you knew exactly how to spot the risk so early on and what to do to intervene, which, we really don't.
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.
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.
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.
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.
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.
"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.
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.
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.
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.
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.
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.
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.
As an example: I'm autistic and I learn inside-out, building larger new concepts out of smaller existing ones; those with Asperger's on the other paw, learn outside-in instead, breaking down larger existing concepts into smaller new ones; both are part of the "autism spectrum", but differ very fundamentally.
Given that the origin of "autism" is simply "thinking that differs from usual", there's no evidence that there is a single underlying cause to find, nor that generalizations across the entire spectrum will reveal much of anything other than coincidence.
I believe we need to individualize new research to the variants that we now know exist, because otherwise we will continue to all-but erase anything that isn't common to the entire spectrum.
[0]: https://www.medrxiv.org/content/10.1101/2024.08.15.24312078v...
This is a really interesting observation - can you expand on this a bit more, please? How did you first notice this distinction?
When, for example, learning a new concept in math or physics, what would outside-in look like vs inside out? Would you characterise neurotypical learning in one way or the other?
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.
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).
> 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.
However, they did a very large cohort study with hundreds of thousands of subjects. The link completely disappears when genetics are accounted for via sibling pairs.[0]
It took almost two whole minutes of Googling for me to disprove this nonsense. Which shows that RFK did less than 2 minutes worth of research before panicking the world.
[0] https://jamanetwork.com/journals/jama/fullarticle/2817406
Bit rich coming from a sockpuppet account created 57 minutes ago...
- exclusively commenting on this thread
- uncritically addressing it from a very specific angle
- mentioning specific things that sound related while not actually connecting them to the overall story with the same rigor
...isn't it?
Shows how shockingly unaware even researchers are on how broad and nonspecific the diagnosis of autism is...
Were these 16 people hypo or hyper sensitive? Which of their five senses were involved? All? Some? Were some senses hyper and others hypo?
Need to start with categorization and specificity before we can make meaningful progress in research
The part I take issue with: "lower brain-wide mGlu5 availability may represent a molecular mechanism underlying altered excitatory neurotransmission that has the potential to stratify the heterogeneous autism phenotype."
Seems like the very premise is flawed, though. Searching for a single global identifier for autism would be like if we spent research time trying to find a single global identifier for cancer. Noble effort... Way harder than spending effort on subcategorization into "lung" and "heart" cancers and working on research for detection of those subtypes.
The only good categorization we have in autism now is severity.
The anecdote I always like to share is Temple Grandin.
She was hyper-sensitive to auditory and tactile senses. The cause for this hypersensitivity was cerebellar abnormalities in her brain. Right now, someone who is hypo-sensitive to sound and touch because of different cerebellar development will also be put in the same bucket diagnostically speaking. There's not gonna be any universal way to detect that though...
To quote her directly:
"It would be my number one research priority, but one of the problems we’ve got on studying this, is that one person may have visual sensitivity, another one touch sensitivities, another one, auditory sensitivities. And when you study these, you got to separate them out. You can’t just mix them all together." https://www.sensoryfriendly.net/podcast/understanding-my-aut...
I'm a dad of two autistic boys who I think would be very different categories. I have friends whose child isn't really autistic, they have a much more rare and specific diagnosis but it's so rare it's hard to get supports so they got him diagnosed as autistic because that criteria is so broad almost anyone can qualify.
Thank you for your work!