The Autism Phenome Project: Toward Identifying Meaningful Subgroups of Autism | Hacker News Reader

The Autism Phenome Project: Toward Identifying Meaningful Subgroups of Autism

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87 pointsSubiculumCode101 comments

I think ADHD and it's subtypes is probably a description of something like 8 different actual neurological causes, which all show up as 'ADHD'. I think one day we will figure out what they are and diagnose them separately, much like how many different viruses all give us cough symptoms and fevers. Wouldn't be surprised if other spectrum disorders show up similarly.

There are lots of incentives at play towards making ADHD as vague and broad as possible.

This is true, because the purposes of diagnosis by clinicians is to help the patient.

However, when it comes to research, its because delineating the various causes of X is very very very hard and long research process.

The incentives are not aligned that way. It might be true that diagnosis helps patients, but diagnoses also helps the clinician by providing a patient. This is the dark side of mental illness research.

Ideal for patients would be receiving the attention of a non-specialist who can be very broad in understanding what sequence of specialist attention is needed, when to pull the plug on that attention, and how to track the overall health and well being of a particular patient especially in regards to anything psychiatric. Virtually no MDs/GPs are going to do that.

The incentive "these people clearly need help of some sort" isn't bad, I think.

But it's bad if we have to pretend we understand something better than we do for people to get the help they need.

I think psychologists largely admit ADHD is a bit of a black box. Maybe genetic, maybe not, specific individual treatments are required, etc. Even meds won't work consistently from patient to patient. That's all fine though because generally some awareness that there's something neurologically aberrant occurring is one of the greatest tools to help cope and strategize. This is where the psychologist can really shine, offering families insight into how to live with ADHD. Whether it be a child, spouse, parent, whatever.

No psychologist I've spoken to or read a book from has claimed to have a firm grasp on what ADHD is. They even admit the diagnosis is very much done "by feel", requiring as much history and cross-reference of family and friends' experiences to be certain.

Well yeah, because it's a social construct.

I'm sorry, just to be clear, do you mean that ADHD is a social construct?

Yes - ADHD is a social construct. But this is not unique to ADHD among mental disorders.

There are many significant findings about the atypical anatomical and neurological development of people diagnosed with ADHD. For example, parts of our brains seem to be smaller [1] and there appears to be less blood flow to the prefrontal regions of our brains [2]. It's well known that our ability to utilize and regulate dopamine efficiently is not on par with our peers - this is why someone with ADHD responds quite differently to stimulants than a neurotypical person does. Otherwise there seems to be various genes associated with ADHD, though that area of research is young. The same can be said with autism.

The pathogenesis of ADHD isn't completely understood, but hard evidence of consistent anatomical, neuronal, and chemical differences is only increasing. There is something real happening without much doubt - the task now is to figure out what and why.

Maybe I'm misunderstanding you when you say social construct, though. I'm not sure if you mean "ADHD isn't real" or "It's a bucket we throw similar types of disorders into". If you mean the latter, I'd agree - I wouldn't be surprised if in 10-15 years we see that sub types can be distinctly identified in some way. I have no idea if at that point we'll need to overhaul these categorizations, but, I suspect we will at least understand the pathology better.

[1] https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0...

[2] https://www.jpn.ca/content/35/5/330

I'm saying that the term "ADHD" is a social construct. We humans have constructed in our mind a category of human behaviors and drawn some fuzzy lines and planted a flag down saying "this is ADHD." Certainly, as you mention, you can draw trends between the two categories (ADHD vs non-ADHD), just as if you were to move from South Africa to Egypt you might notice that most of the people look different. But that doesn't make "Egypt" or "South Africa" any less of a human construct.

The idea that ADHD is some abberant way of being that ought to be medicated into a teleological more ideal way of mental being is also, completely, a human construction - you can't get that conclusion just by looking at brain blood flow or anything like that.

I see where you’re coming from. I’m not sure where you’d draw the line with things being human constructs, and I’m not sure if it being a construct really detracts from it much.

I do agree about it not inherently being a problem that needs to be medicated. I personally only use meds when I need to be more “normal” and cut through the fog that daily life and tasks seems to generate for me. Sometimes I will develop a backlog of tasks and it’s helpful to cut through it.

I get the feeling that I was born in the wrong place at the wrong time, so to speak. It seems ADHD is present but much more tolerated in some cultures such that it doesn’t cause the person with ADHD as much stress or anxiety as they grow older. Like you suggest, these people are just people and though they’re different in some ways, it’s still within the bounds of normality.

It seems to be once you put ADHD brains into uncomfortable environments that it becomes problematic. Otherwise there is plenty of potential for it to be advantageous in many ways.

Part of this (from what I understand) is that casting a wide net and offering treatment can be an incredible preventative for children. So long as you aren't by default shoveling meds into the patient or telling them something is wrong with them (thus making false-positives almost certainly destructive diagnoses), a lot can be gained by guiding people with ADHD towards treatments.

There is a staggering amount of progress and recovery to be made, or damage to be avoided, by diagnosing ADHD. I'm all for a wide net so long as people getting caught in it are treated properly on an individual basis.

> I think ADHD and it's subtypes is probably a description of something like 8 different actual neurological causes, which all show up as 'ADHD'.

This is the case with I believe probably the majority of psychological illnesses that have not yet been nailed to a clear biological cause.

Schizophrenia definitely has a bunch of sub-types. As does anxiety. As does whatever is sociopathy/psychopathy. ADHD included.

Over time, individual types of each of these mental illnesses will be carved out from the general type and tied to specific biological causes, thus making the vague categories even smaller.

There's a tendency to for diagnoses to double duty, both as description and explanation. Why does he do those things? Because he's autistic. And why do we call him autistic? Because he does those things.

It's especially bad for things which are defined by "at least n of these m things", including depression, addiction, and a ton of other psychological diagnoses. Are we getting any wiser from such definitions at all?

(But there's the issue of insurance, or rationing assistance more generally, which compels us to keep using these non-explaining diagnoses.)

This was actively damaging to me; I didn't get diagnosed (and subsequently receive help) until I was 33 because I'm ADHD-PI and was only familiar with stereotypical ADHD-PH, which is very much NOT me. I really hope there's more differentiation someday.

Yeah, pretty common AFAIK with the 'twice exceptional' (gifted and have other issues). The medical system is not as focused on helping people who are getting by well enough and there isn't anything obviously wrong with them.

I've heard some discussion around reclassifying certain mental illness into clusters - things like depression and anxiety have extremely high levels of comorbidity.

If dermatologists worked like psychiatrists they wouldn't be able to tell acne and chickenpox apart (and they'd treat both with face powder).

One of the worse example is schizophrenia, which is attributed if you have at least two symptoms out of a list of five (meaning that people with totally distinct symptoms end up with the same diagnosis). There were genome-wide association studies in the 2010's that identified 7 or 8 distinct transcription factor networks with polymorphisms associated with a risk of schizophrenia. Every network is associated with the same symptoms.

In other words schizophrenia is likely at least 7 distinct diseases that are so orphaned they don't have a name.

Another example is eating disorders, where both bulimia and anorexia are probably underpinned by the same pathology that involves an auto-immune response following a cross-reaction to a bacterial protein that mimics a satiety hormone.

I'm a middle-aged adult now, but as a child I had mild autistic traits. Socio-economics, along with 1980's medicine, meant it was never picked up. I wonder if selection methods based entirely around childhood diagnosis may miss certain sub-groups.

Author, what about the so-called 'savant' type of autistic person? Or even the anecdotal 'high functioning, high IQ' sub-group? Did your study find any evidence of these?

It took until well into my 30's before my autistic traits heavily impacted my life. Looking back, I realised there had been a gradual snowball effect of oppressive environmental factors, incrementally pushing me further and further into "an autistic corner" - starting from that initial seed of childhood traits, but with the outcomes seeming as much developmental as genetic.

Which, as an aside, seems to revolve as much around how other people (the world at large) treat the individual, as around factors internal to the autistic person themselves.

Sampling bias is always an issue. For example, our research has an inordinate portion with intellectual disability...probably as a function of recruiting young children with autism (those more severely affected tend to get diagnoses early).

All good points.

I am a co-author. I would be pleased to answer questions.

My amateur understanding is that Autism is now considered a spectrum. With that in mind, do meaningful subgroups map to range(s) on the numberline that is the spectrum? Or, are meaningful subgroups distinct categories that do not correlate to one's score?

The autism spectrum may have originally been construed as one dimensional, from minor to profound autism. However, I would say now that 'spectrum' is predominately understood in the autism research community as meaning "diverse." Diverse presentations, diverse symptoms, diverse co-occurring symptoms, diverse lived experiences, diverse outcomes, a la if you've met one person with autism, you've met one person with autism.

The Autism Phenome Project is predicated on the idea that there may be some underlying homogeneity so that we might identify clinically meaningful subgroups within the autism "spectrum"/"diversity", which may help us develop better targeted interventions, support services, etc.

Great question.

So in keeping with the light analogy, it's a gamut then.

No, gamut : discrete :: spectrum : continous

Since when is a gamut discrete?

I think the original meaning of gamut - the full set of musical notes in a scale – refers to a discrete series. But in color theory the gamut is the complete set of colors that can be reproduced by a device (or which is present in an image), and is continuous (although you could probably argue for discrete depending on how colors are defined in a particular model.)

I think there's a lot of history of using the term "spectrum" to mean a single dimension. See https://en.wikipedia.org/wiki/Spectrum for some examples and counterexamples.

I suspect it will create confusion to use the same word for a multi-dimensional meaning, especially when there is preexisting literature about the "autism spectrum" that used the single-dimensional meaning. I think it would be ideal to use another term.

It seems that the thing we're talking about is "a cluster of imperfectly correlated traits". Googling a bit, I see "syndrome" as one possibility (although it may carry the connotation of a disease, although that may be inevitable with autism). "Trait cluster"?

(If one wants to dig into the light metaphor: The thing you're looking at is a beam of light. You use a prism, and that splits the beam into its constituent frequencies. When you shine the light through a prism onto paper, the resulting image is a spectrum. But the original light beam itself is not a spectrum. Thus, the most appropriate way to use "spectrum" in connection with autism would be for someone to take a test that measures several different traits, and then the test results are the "spectrum". I'm not going to try to fight for that definition, though.)

Definitely. Scientific understanding, thankfully, evolves!

It's a multi-dimensional spectrum, it can't be captured adequately by a single number.

I was not aware of this. About a decade ago I was diagnosed using a questionnaire and received a single score on a numeric scale from 0 to 35. I think the maximum score was in either the low to mid-30's, I don't recall exactly what it was. I don't remember what the assessment was called, but it was an actual standardized test given by a psychiatrist.

I haven't kept up with the current state of understanding, but now I am intrigued and I wonder how I score on those other dimensions they now asses.

It's probably because you scored high on several factors.

Instead of one score, think of it like a cumulative score. You have, let's say, 7 factors all scored from 1 to 5. If the score for being diagnosed with Autism is 21, for example, there are many ways to achieve that. Three areas with a 5 and then a single 3 in any other area would have you diagnosed. Similarly if you score 3 across the board.

Basically, they're saying when you hit that minimum overall score, your factors put you that far divergent from most people that it's at least noticeable.

Nonsense. Just uses bit flags. :)

love it.

I'm a psychiatrist just dropping in to say thanks for doing this work. The current breadth of the diagnosis makes generalizations about treatment interventions / prognosis less helpful than it could be.

Thank you.

I've been diagnosed bipolar, but everything I know about my non-neurotypical character plus what I've observed in computer programmers who've been diagnosed with autism tells me that I'm autistic.

Is it possible for autism to look like bipolar disorder type II (no manic psychosis)?

Bipolar disorder and autism do frequently co-occur, but I am not qualified to speak about whether type II is more or less prevalent.

One of the reasons I am interested in autism is because it frequently co-occurs with ADHD, BP, Anxiety disorders, and pretty much any and all other developmental disorders, which suggests that beyond "autism is a spectrum", all developmental disorders are also belong on that spectrum.

> Bipolar disorder and autism do frequently co-occur

Thanks for responding. I thought it was a offbeat idea of mine, but now I'm going to research it.

iirc, women with autism in particular are often misdiagnosed with bipolar disorder or borderline personality disorder.

> autism is because it frequently co-occurs with ADHD

Fun-fact: Until very recently, psychiatric handbooks proscribed comorbid diagnoses of ASD and ADHD - which is outrageous. Especially in the 1990s.

Mental conditions can have a lot of symptom overlap, which is why if you have a suspicion, you should get assessed by a neuropsychologist, and not the simple kind of 30 minute self done questionnaire type, but a proper 1 to 3 day assessment.

ADHD, Autism and Sensory Processing Disorder all have overlapping symptomology, and sometimes people can have all 3. You might not have autism, but you have might sensory processing disorder and adhd which can still effect your ability to socialize and make friends for example, which might make you think you have autism when you dont. Also if you dig into the DSM, you'll see that things like ADHD have subtypes too. If you suspect it, you should check it!

> all have overlapping symptomology

Yes, I did a bit of searching and it appears I may have both. My extreme focus and interest in computer programming has made me successful, but doesn't feel manic at all. It feels like a form of autism that I saw when I met some trainspotters. On the other hand, I do get manic and talk a lot, express a lot of far out ideas, want to spend money - classic manic symtoms - but I don't write very good code in this condition. I do and say dumb things, which my introverted, focused, autistic self later feels is out of control and embarassing.

> talk a lot, express a lot of far out ideas, want to spend money

That might be impulse control from ADHD and not mania. Hyperfocus is also another aspect of ADHD. Introversion can also come from ADHD too, and if you get medications, you might notice yourself becoming more extroverted. Or you could have some autism. This is why you should go get a proper assessment and stop doing the equivalent of Dr. Web MD on yourself.

If it helps you, I'm diagnosed with bipolar and Asperger's.

That does help. So it is possible. Don you care to share the diagnostic criteria you met?

I'll email you.

It's possible to be diagnosed for bipolar type II together with a plethora of other things in the DSM that I'm not qualified to list. But in my anecdotal experience dealing with diagnoses, there's at least like five or six major diagnoses that sometimes co-occur with bipolar type II.

If you think you fit the autism umbrella I would recommend you seek a specialist that is willing to work with you on treating those symptoms. The whole deal about this diagnoses is helping the people who get them, it's not just a very convoluted personality test or something. You have to go follow the path that actually helps you and others, and the mental health professionals job is navigating that with you.

Thank you. I don't necessarily need a diagnosis, I'm just looking for an explanation for some of my non-neurtypical traits that bipolar doesn't account for. I don't blame my pdocs for not being to tease out the difference because it's subtle and I couldn't describe it well. But it might be interesting to investigate further now that I know it's possible.

I’m bipolar type 1 and I share a great many traits with people who are autistic.

I’ve narrowed down the difference in our experiences into the same sensory processing issues from opposite directions.

One example: Very broad, inaccurate terms, my friends do not understand other people’s emotional state. I understand emotions very deeply but my own emotions are over-reactive and intense, they are useless in reading and understanding other people.

Both my autistics friends and I have had to learn social skills by logic, rather than intuition.

So is it possible that autism might be more than one disease? Instead of a spectrum, in the future do you think that one or more of these subgroups would be broken out into newly classified diseases?

For instance a significant subgroup has sleep issues and elevated levels extra-axial CSF. Another had significant GI problems. Does it seem like those subgroups may have autism from different causes, and maybe different diseases?

Hopefully this gets posted: HN often rate limits my posts.

In short, yes. Autism may one day be meaningfully classified as different conditions that share some similar symptoms, but have different causes, outcomes, etc. The common symptoms of autism tend to be seen in high-level cognitive functions, that depend on a lot of subsytems, if you will. Car analogy: A car may exhibit the same symptom (won't start), but the cause can be different (out of gas or a dead battery). But this analogy can easily be misconstrued to mean that autism is about being broken. Emphatically, it is NOT. This brings me to a final comment of your post: Autism is not a disease.

Much of the autism spectrum represents valuable neurodiversity that does not impact their quality of life, and actually provides a net benefit to themselves and to society by allowing diverse thinking styles and perspectives. However, I will venture to say that some aspects of the spectrum do need to be addressed like a disorder: severe intellectual disability, severe anxiety, these can be really impactful on QoL.

Thank you for your response, I really appreciate it!

> Autism is not a disease.

I will try to keep this in mind in the future.

This is like trying to say that because some blind people have improved auditory function, and because that is sometimes useful to society, deafness is "not a disease". We can have sympathy for autistics and try to make reasonable accomodations while also trying to cure it so nobody in future generations is born that way.

I'd just say that it is a sensitive topic with many legitimate stakeholders and perspectives.

So you’re basically promoting eugenics ?

My brain works different from yours, it is not a disease and doesn’t make me disabled. Just because there are fewer of us than there are of you doesn’t mean we don’t have a right to exist.

Autism is not comparable to blindness in any meaningful way, so no.

I've got an anecdote from a nurse that when autism was registered as a disability the diagnostic criterion were loose enough that it enabled practitioners to fudge the numbers in favor of the families enabling them access to the special needs care and support systems which would otherwise be crippling.

If this is true, I would expect it to function as an umbrella describing symptoms rather than pathology.

EDIT: I should clarify that I'd like SubiculumCode's input on this if they find it worthy of discussion.

There are a couple of motivations. A diagnosis of autism opens up support services that are often needed, one way or another. Therefore, I'd acknowledge there is probably incentives for the clinical diagnostic process to favor limiting false negatives. Nevertheless, when it comes to the gold standard of autism diagnosis (i.e. the ADOS), diagnostic sensitivity has increased over the years by zeroing in one the symptoms that autistics tend to share.

The implications of this increased sensitivity has been to 1) autism prevalence has gone up , and 2) the average "severity" of autism (ADOS CSS scores) has decreased. This has also led to conflicts within the autism advocacy community: e.g. diversity vs disorder.

> A diagnosis of autism opens up support services that are often needed, one way or another.

In the LA area, there's a 6-month wait list to see an in-network child psychologist or neurologist that can give an autism diagnosis. Booked in November 2021, our appointment is in March 2022 and therapy classes are also wait listed. We found out-of-network providers but they are charging from $2,500 to $7,000 along with a 3-month waitlist.

> Gastrointestinal (GI) concerns are frequently reported by parents of autistic children and may be related to immune dysregulation (Buie et al., 2010). This is particularly concerning because it may be more challenging for autistic children to verbalize or communicate physical pain, leading to lack of appropriate medical care.

Is this more challenging "to verbalize or communicate physical pain" because of the lack of understanding we currently have for GI-related issues? Having dealt with several GI doctors who just want to prescribe PPIs for everything, I am curious.

The citation given seems to suggest that is the reason, but it isn't clear:

> Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are incompletely understood.

A large proportion of autistics are non-verbal or have intellectual disability. They therefore may not be able to effectively communicate that they are in pain. GID may be misdiagnosed then as other externalizing affective behaviors.

The issues are purely that of communication and not the lack of diagnostic tools?

This was not my specialty, but I think both.

Very interesting! It looks like the paper examines characteristics mostly independently to form groupings. Have you considered examining all the characteristics at once using something like t-SNE to see if any new subgroups appear?

t-SNE is a cool technique, even if some of the parameters require manual judgment/tuning. I've actually been thinking about taking our various groupings and trying a combined analysis, maybe with multivariate distance matrix regression. One issue is that labels are not exclusive, some individual may belong to several.

I'm autistic. Have you considered doing a study using whole geneome sequencing? I had my genome sequenced to try to get to the bottom of what's going on for me (outside of autism) and after running some data mining on it lo and behold, shows a very high correlation between genes associated with autism.

One thing that I don't see talked about a lot is the link between autism and parkinsons.(https://pubmed.ncbi.nlm.nih.gov/26322138/) My maternal grandmother and mother had Parkinson's and I'm sure my grandmother and her sister were on the spectrum as well (although they didn't really diagnose that form of autism back then). This may link into the subtype of autism you're talking about though with autoimmune as my mother has celiac and I have HLA mutations.

Also noticed you were talking Amygdala Volume , but have you seen this? https://pubmed.ncbi.nlm.nih.gov/28689329/ This really makes me think about your paper because it's linking specifically right sided decrease of Amygdala Volume to a form of autism with anxiety. This makes me think about how autism is often missed in girls. I'm aware of this fact because I also have the right sided decreased volume after uploading a Brain MRI here: brainkey.ai . This, along with Whole Genome Sequencing (I got mine done at nebula.org) could really set the stage for wider studies at a fairly low cost.

Anyway thanks so much

The Autism Phenome Project has collected genetic data from all participants. Whole genome sequencing is starting to be processed. Getting funding was a bit tricky, somewhat surprisingly. The issue is N. We have a good sized cohort generally, but genetic analyses often require very large samples...mostly because individual genes only contribute small increases in risk for autism. Right now we are hoping to take a approach of looking for rare variants that have outsized effects.

Autism and Parkinson's: I had not known that. My grandmother also has Parkinson's. Thanks for the link. I will say that autism is a fairly new diagnosis, and thus not many with an autism diagnosis are old enough yet to get obvious Parkinson's. However, this and other aging topics WILL be a very hot topic of autism research in the next 20 years.

Thanks for the paper link. We think so too, at least in part. I point you to this paper [1], where we used Fear Potentiated Startle in Children With Autism: Association With Anxiety Symptoms and Amygdala VolumeWe have another paper that is under review that specifically looks at types of anxiety (DSM vs distinct anxiety) and amygdala development. Unfortunately, I don't have a shareable version yet.

[1] https://www.researchgate.net/publication/347985459_Fear_Pote... ]

Is there any way I can contribute my WGS data? I'll request it on researchgate! Thanks so much! I have always had an insane startle response since I was a child, to the point that I'd scream and fall out of a chair if my parents entered the room and said hello when I was in the middle of something! From what I understand with these papers children are born with the decreased amygdala volume. I feel like the other part of it is going through life with severe anxiety, autism, and fearfulness and the negative reactions to it are just a vicious cycle.

Thank you for the kind offer. There may indeed be repositories out there to which you could contribute. In terms of the autism phenome project, probably not. For one, the deep phenotyping we do (i.e. collect a lot of data) is a critical component, Also, there is actually a fair amount of variability in the methods to doing DNA sequencing (not an expert), that could pose issues. But again, thank you for the kind offer.

No problem. I'm not sure of other places, but the cost to me was 300 dollars out of pocket at Nebula.org. They use 30x sequencing which is considered clinical grade and they also offer 100x sequencing, but from what I understand this is pretty much overkill. You can use software to see the areas that had worse coverage if there are any questions.

If you were doing this at scale I'm not sure what Nebula.org offers past some app stuff. All of the useful information I got on my own through using Exomiser/Enrichr on the raw data, although Nebula does have an interesting part to it where you can see where you fall in terms of risk SNPs in terms of percentile to other users (I got 90% on their Systematizing/Autism one there: https://nebula.org/blog/genetics-of-systemizing-in-autism/). When I shipped my sample they used the lab AKESOgen to do the work of sequencing, so maybe you could contact them directly if you had any questions about projects like this.

My younger brother is diagnosed as what can currently only be described as "moderately functioning" autism and I cannot thank you enough for starting in on this very important research.

Thank you.

Does the scope of the study include gathering data to support analysis of the causes of autism? e.g. parental genetics or environmental factors?

We collect a ton of information, including genetics, family histories, etc. We are thoroughly cursed by dimensionality.

Is there any computer-based clustering/analysis you did of the individuals? Sometimes this can reveal a typology of the underlying root causes. Maybe you could see which cluster of symptoms predict others, thus suggesting root causes....

I am not sure what you mean by "computer-based." We definitely have done various types of analyses: Support vector machines, latent profile analysis, multivariate distance matrix regression, and others. The field as a whole is VERY in-tune with ML, clustering, etc methods...because we need it. Results are somewhat mixed, but this is due to lots of noise in the data, limited samples, and overall copmplexity etc.

Cool paper!

Can I bottom line this as: there's nothing here so far, i.e., there are no clinically meaningful subgroups.

I don't mean this as a negative or to put down the awesome work, but this seems like a fair summary?

When I feel my most cynical perhaps, but no I don't think that is the bottom line of the paper. "For example, disproportionate megalencephaly at age 3 may provide early clues to parents about children who may require higher levels of support, or individuals with autism distinct forms of co-occurring anxiety may benefit from autism-specific anxiety interventions." The naive hope we all had was that we'd collect a bunch of data and identify all the important clusters unsupervised. Reality is that identification meaningful subtypes will involve examining one or several at a time (per grant), even if that cluster might only represent <1-5% of all autistics.

Is there a specific reason the study focusses on children ? As an autistic adult it often feels like we don’t exist, most resources and research seem to focus exclusively on autistic children, as if it just disappears when we grow up.

I've heard that there is more of a dearth of autism research in adults when it comes to behavioral interventions, however, the vast majority of autism MRI research actually occurs with adolescent and adult participants actually. Our research begins as early as two year old because this is a period of profound brain development, development that has life long implications. Research strongly suggests that interventions that occur early have the largest impact...because they are still developing and open to changing the course of development.

A well written paper. Glad to see you included females with autism. Typically research papers under-represent or ignore females with autism, which is plain wrong.

I used to work as an EEG technician, and came across some autistic children.

Was there any consideration for using quantitative EEG analysis to help identify subgroups of autistic children?

The quality of life of a female with Asperger’s is dramatically higher than that of a male. My whole family has it and it’s clear. There’s something about the female brain that is not impacted the same way. The liberal media loves to ignore this and they lean in super hard on “shielding” or whatever where they say the discrepancy is explained by the fact that females just deal with it better. And the rest of the gap is explained by sexism, of course. It’s a fucking lie and it’s bullshit.

My wife has Asperger's and had a hell of a time getting bullied in school.

Women with Asperger's are also more likely to get into abusive relationships and/or abuse drugs.

You sound really angry in this comment and make a lot of assumptions.

Do you feel that the others in your family afflicted with Asperger's had it easier due to their gender? Seems to be a bit of a sore point for you.

Over the years I have become very attuned to the signs of autism. A lot of people who have autism don’t show any obvious signs and are undiagnosed. There are absolute tons of women who have autism and nobody realizes it. The two most common symptoms are being “bossy” or having a hard time keeping their observations to themselves and also being overly sexually promiscuous. These women have sons who are on the spectrum almost without variation. And these females are all very well adjusted and often have very good careers. It’s kind of maddening when you see these women giving birth to tons and tons of men who are super disadvantaged and often end up really badly, much worse than their mothers. Once you learn how to spot it you see it absolutely everywhere. I think it’s unfair that boys are being fucked so hard and there’s no help or recognition for their situation.

So no, women who have diagnosed autism do poorly but as everyone knows, even the liberal media, the disease doesnt treat the sexes equally.

I think you are projecting anger. I always become frustrated when the truth is brushed aside because of petty political or moral reasons. The truth is the light in this dark world.

Asperger's is just part of the spectrum,and the experiences of individuals on the spectrum vary widely. Calibrated autism severity scores in our sample are pretty equivalent in males and females, but there are differences between the sexes.

> Calibrated autism severity scores in our sample are pretty equivalent in males and females

Did the "calibration" cause you to find what you wanted to find? How do you even calibrate something like that.

No. It was not calibrated to equalize genders, but for language ability and age.

https://www.spectrumnews.org/news/clinical-research-new-test...

I'm interested in the neurological differences in the male and female brain as they relate to ASD. If we accept the findings in Ingalhalikar et al.[0] it seems to me like there is some explanatory power in the evident disproportion of occurrence of ASD in females. On one hand it appears the female connectome tends to favor a strategy of "indiscretion" whereas men do the opposite, instead relying on discrete processes. If we follow another study, they reason that the increased male variability in brain development may lead to susceptibility of certain disorders[1]. From the "purely neurological" pathology, is this something that might fit your findings? Where, if women aren't less susceptible then perhaps men are in terms of brain development?

And then we might consider the process of socialization as well, which I'd expect could lead to differing outcomes on the nose.

I don't know how extensive the issue is, or why it is, but I read a Wired article that indicated most pain medication studies focused exclusively on male subjects, and 96% did not compare differences between genders[2]. But also indicated differences in the way that pain is handled. If we extrapolate this into a trend, what else might we missing in the long run with such an oversight? Not to say that it is one, but if.

[0] https://www.pnas.org/content/111/2/823 [1] https://pubmed.ncbi.nlm.nih.gov/33044802/ [3] https://www.wired.com/story/womens-pain-is-different-from-me...

This is absolutely correct. Early medical research was dominated by the assumption that males and females will react similarly to drugs, which is just not the case. Our labs has focused on recruiting females with autism in part because concerns of equity, but also because it might give us insight of the causal mechanisms underlying autism.

Thank you for the kind words. We do, in fact. Here is a link to a recent paper using ERP: https://www.sciencedirect.com/science/article/pii/S002839322...

My 3 year old has ASD. I'm interested the finding about disproportionate megalencephaly, as his head is pretty big (but he's also rather tall). Suppose I wanted to see if he falls into the >1.5 SD cerebral volume/height bucket. Is there a way to meaningfully approximate it with his head circumference and height?

The correlation between head size and brain size after accounting for height (which is positively related to brain size) is not as strong as one would think.

We are specifically recruiting young children with larger head sizes to be part of our studies. If interested, please contact us: HS-TeamAPP@ucdavis.edu https://health.ucdavis.edu/mindinstitute/research/autism-phe...

I am HFA and have EDS, which is a not-uncommon combination. You should consider co-morbidities like EDS.

I had not heard of EDS. I will take a look. At what age is EDS usually diagnosed?

> Intellectual functioning is one of the most heterogeneous aspects of autism (Maenner, 2020). In the APP, we identified subgroups based on the trajectory of intellectual functioning across early childhood (Times 1–3) (Solomon et al., 2018). Four distinct trajectories were identified: two groups, comprising 26 and 18% of the sample, respectively, had IQs in the intellectual disability range at both time points; a third group (22%) had IQs in the normal range at both time points. Of particular interest, a fourth group, comprising 35% of the cohort, initially had IQs in the intellectual disability range but made significant gains (34 points) to have IQs in the normal range by age 6–7.

Are there none with above normal IQ? For your purposes, does above normal IQ rule out "autism" by definition, as in, such will never be included in any groupings?

Given debate whether Asperger syndrome is a thing, and what seems to be emerging consensus Asperger's should be collapsed into autism spectrum^H^H^H diversity, what grouping contains those with well above normal language expression and intelligence?

I imagine such grouping to be of interest to this HN community:

"In the social world, there is no great benefit to a precise eye for detail, but in the worlds of maths, computing, cataloging, music, linguistics, engineering, and science, such an eye for detail can lead to success rather than failure."

https://web.archive.org/web/20081217140628/http://autismrese...

- and -

"JPMorgan Chase’s Autism at Work program has helped the company fill a talent gap in its software engineering and quality assurance departments. When the program first started in 2015, a cohort of five employees on the spectrum were hired. Within the first six months, those employees were 48% more productive than employees not on the spectrum who had been at the same job three to ten years."

https://www.benefitnews.com/news/jpmorgan-chases-autism-at-w...

Yes, we do have above average IQs in the sample with autism that is not Asperger's. Intellectual disability is a co-occuring condition that is not a criterion for autism.

I have a non-verbal little brother with autism. I've wanted to keep tabs on state-of-the-art autism research. This seems like a great entrypoint. Thank you.

Such a meta project. Autists are splitters. Empaths are lumpers.

I have severe schizoaffective disorder and the past three years of my life have been dedicated to learning more about psychiatric disorders. Most people have no idea just how rudderless we are. It’s the equivalent of people thinking rickets was a failure of moral fiber in the olden days. We are truly, truly living in medieval times.

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