10 ms·

The Autism Phenome Project: Toward Identifying Meaningful Subgroups of Autism

87 points by SubiculumCode 5y ago

SubiculumCode 5y ago
I am a co-author. I would be pleased to answer questions.
- BitwiseFool 5y ago
  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?
  - SubiculumCode 5y ago
    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.
    - CarVac 5y ago
      So in keeping with the light analogy, it's a gamut then.
      - gowld 5y ago
        No, gamut : discrete :: spectrum : continous
        CarVac 5y ago
        Since when is a gamut discrete?
        thedailymail 5y ago
        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.)
    - waterhouse 5y ago
      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 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.)
      - SubiculumCode 5y ago
        Definitely. Scientific understanding, thankfully, evolves!
  - yed 5y ago
    It's a multi-dimensional spectrum, it can't be captured adequately by a single number.
    - BitwiseFool 5y ago
      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.
      - bena 5y ago
        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.
    - jancsika 5y ago
      Nonsense. Just uses bit flags. :)
      - SubiculumCode 5y ago
        love it.
- phren0logy 5y ago
  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.
  - SubiculumCode 5y ago
    Thank you.
- okareaman 5y ago
  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)?
  - SubiculumCode 5y ago
    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.
    - okareaman 5y ago
      > 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.
      - mercer 5y ago
        iirc, women with autism in particular are often misdiagnosed with bipolar disorder or borderline personality disorder.
    - DaiPlusPlus 5y ago
      > 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.
  - novok 5y ago
    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!
- melissalobos 5y ago
  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?
  - SubiculumCode 5y ago
    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.
    - melissalobos 5y ago
      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.
    - collegeburner 5y ago
      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.
- css 5y ago
  > 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.
  - SubiculumCode 5y ago
    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.
    - css 5y ago
      The issues are purely that of communication and not the lack of diagnostic tools?
      - SubiculumCode 5y ago
        This was not my specialty, but I think both.
- kens 5y ago
  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?
  - SubiculumCode 5y ago
    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.
- jklinger410 5y ago
  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.
  - SubiculumCode 5y ago
    Thank you.
- cupcake-unicorn 5y ago
  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/ 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/ 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
  - SubiculumCode 5y ago
    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_Potentiated_Startle_in_Children_With_Autism_Spectrum_Disorder_Association_With_Anxiety_Symptoms_and_Amygdala_Volume https://www.researchgate.net/publication/347985459_Fear_Pote... ]
- jl6 5y ago
  Does the scope of the study include gathering data to support analysis of the causes of autism? e.g. parental genetics or environmental factors?
  - SubiculumCode 5y ago
    We collect a ton of information, including genetics, family histories, etc. We are thoroughly cursed by dimensionality.
- esens 5y ago
  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....
  - SubiculumCode 5y ago
    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.
- light_hue_1 5y ago
  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?
  - SubiculumCode 5y ago
    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.
- Aaargh20318 5y ago
  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.
  - SubiculumCode 5y ago
    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.
- neurotech1 5y ago
  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?
  - supperburg 5y ago
    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.
    - sjcoles 5y ago
      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.
      - supperburg 5y ago
        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.
- vechagup 5y ago
  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?
  - SubiculumCode 5y ago
    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-phenome-project/index.html https://health.ucdavis.edu/mindinstitute/research/autism-phe...
- empressplay 5y ago
  I am HFA and have EDS, which is a not-uncommon combination. You should consider co-morbidities like EDS.
  - SubiculumCode 5y ago
    I had not heard of EDS. I will take a look. At what age is EDS usually diagnosed?
- Terretta 5y ago
  > 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://autismresearchcentre.com/docs/papers/2002_BC_ASDisability.pdf 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-work-program-opens-doors-for-those-on-the-spectrum https://www.benefitnews.com/news/jpmorgan-chases-autism-at-w...
  - SubiculumCode 5y ago
    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.
novok 5y ago
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.
- TopRattata 5y ago
  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.
  - novok 5y ago
    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.
- whimsicalism 5y ago
  There are lots of incentives at play towards making ADHD as vague and broad as possible.
  - SubiculumCode 5y ago
    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.
    - bdamm 5y ago
      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.
dayvid 5y ago
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.
lindsaywaterman 5y ago
Such a meta project. Autists are splitters. Empaths are lumpers.
supperburg 5y ago
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.
oonerspism 5y ago
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.
- SubiculumCode 5y ago
  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.

87 points by SubiculumCode 5y ago

SubiculumCode 5y ago

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

BitwiseFool 5y ago
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?
- SubiculumCode 5y ago
  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.
  - CarVac 5y ago
    So in keeping with the light analogy, it's a gamut then.
    - gowld 5y ago
      No, gamut : discrete :: spectrum : continous
      - CarVac 5y ago
        Since when is a gamut discrete?
        thedailymail 5y ago
        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.)
  - waterhouse 5y ago
    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 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.)
    - SubiculumCode 5y ago
      Definitely. Scientific understanding, thankfully, evolves!
- yed 5y ago
  It's a multi-dimensional spectrum, it can't be captured adequately by a single number.
  - BitwiseFool 5y ago
    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.
    - bena 5y ago
      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.
  - jancsika 5y ago
    Nonsense. Just uses bit flags. :)
    - SubiculumCode 5y ago
      love it.
phren0logy 5y ago
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.
- SubiculumCode 5y ago
  Thank you.
okareaman 5y ago
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)?
- SubiculumCode 5y ago
  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.
  - okareaman 5y ago
    > 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.
    - mercer 5y ago
      iirc, women with autism in particular are often misdiagnosed with bipolar disorder or borderline personality disorder.
  - DaiPlusPlus 5y ago
    > 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.
- novok 5y ago
  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!
melissalobos 5y ago
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?
- SubiculumCode 5y ago
  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.
  - melissalobos 5y ago
    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.
  - collegeburner 5y ago
    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.
css 5y ago
> 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.
- SubiculumCode 5y ago
  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.
  - css 5y ago
    The issues are purely that of communication and not the lack of diagnostic tools?
    - SubiculumCode 5y ago
      This was not my specialty, but I think both.
kens 5y ago
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?
- SubiculumCode 5y ago
  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.
jklinger410 5y ago
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.
- SubiculumCode 5y ago
  Thank you.
cupcake-unicorn 5y ago
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/ 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/ 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
- SubiculumCode 5y ago
  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_Potentiated_Startle_in_Children_With_Autism_Spectrum_Disorder_Association_With_Anxiety_Symptoms_and_Amygdala_Volume https://www.researchgate.net/publication/347985459_Fear_Pote... ]
jl6 5y ago
Does the scope of the study include gathering data to support analysis of the causes of autism? e.g. parental genetics or environmental factors?
- SubiculumCode 5y ago
  We collect a ton of information, including genetics, family histories, etc. We are thoroughly cursed by dimensionality.
esens 5y ago
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....
- SubiculumCode 5y ago
  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.
light_hue_1 5y ago
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?
- SubiculumCode 5y ago
  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.
Aaargh20318 5y ago
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.
- SubiculumCode 5y ago
  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.
neurotech1 5y ago
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?
- supperburg 5y ago
  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.
  - sjcoles 5y ago
    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.
    - supperburg 5y ago
      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.
vechagup 5y ago
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?
- SubiculumCode 5y ago
  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-phenome-project/index.html https://health.ucdavis.edu/mindinstitute/research/autism-phe...
empressplay 5y ago
I am HFA and have EDS, which is a not-uncommon combination. You should consider co-morbidities like EDS.
- SubiculumCode 5y ago
  I had not heard of EDS. I will take a look. At what age is EDS usually diagnosed?
Terretta 5y ago
> 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://autismresearchcentre.com/docs/papers/2002_BC_ASDisability.pdf 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-work-program-opens-doors-for-those-on-the-spectrum https://www.benefitnews.com/news/jpmorgan-chases-autism-at-w...
- SubiculumCode 5y ago
  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.

novok 5y ago

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.

TopRattata 5y ago
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.
- novok 5y ago
  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.
whimsicalism 5y ago
There are lots of incentives at play towards making ADHD as vague and broad as possible.
- SubiculumCode 5y ago
  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.
  - bdamm 5y ago
    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.

dayvid 5y ago

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.

lindsaywaterman 5y ago

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

supperburg 5y ago

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.

oonerspism 5y ago

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.

SubiculumCode 5y ago
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.