Would this mean gene-therapy could potentially undo autism?
Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?
> since I believe it's now actually agreed upon that autism rates actually ARE increasing
why do you believe that? I'm not aware of any recent research that would point in that direction and disprove the very plausible hypothesis that the increase is an effect of changing diagnosis criteria and increased attention for the topic.
Yes, I'd like to know where you are getting that the actual rates are increasing. My wife and I (parent's of a daughter with autism) laugh how every year they claim the numbers increase - 1/100, then 1/50, etc. These are numbers marketed by Autism Speaks and other organizations to make autism appear more wide spread and increase their funding. This does nothing but hurt people with more severe autism. Widening the net so wide so that any social difficulties is considered autism just reduces the availability of services for children with "real" autism. Autism is a spectrum, with people who are completely non-verbal constantly stemming to people with Asperger's Syndrome who excel but have some social difficulties. They really should be distinguished.
> Widening the net so wide so that any social difficulties is considered autism
That's an oversimplification of the situation, both the autism spectrum (including the now-reclassified Aspergers), and the entire rest of the DSM. Some of those mental disorders also result in social difficulties.
I'm sure you would like more help for only "deserving", specific children like yours, but increased access means more schools that are able to handle IEPs, more teachers able to cope with special needs children, more understanding by all that yelling at a non-verbal stimming child is counterproductive, It means more attention paid by society, more research into the problem, resulting in figuring out the causes of autism.
It really is a spectrum, and limiting help and research to only individuals to non-verbal, body-rocking, non-stop stimming makes it very hard for research to progress - those individuals are very difficult to communicate with! Someone who's limits of communication is PEC cards, is not able to give any useful sort of description of how a particular medication is affecting them.
We are starting to recognize that it is, as least partially, an anxiety disorder, of which we already have a number of doctor prescribed medications, with anecdotal successful treatment for autism.
I'm not sure what you mean by increased access. The public school system has very limited funds and personnel. There are some schools with no dedicated reading specialist for example (ever fewer have occupational therapist or autism specialist trained in ABA or other methods). In the real world you have to make decisions on what kids need extra help. It would be great to say everyone gets it but that's not feasible.
I'm all for researching across the spectrum and more public awareness.
Let's separate facts from feelings. At the end of the day it really is irrelevant what indirect emotional consequences the facts have, all that matters is that we get the ones that happen to be true so that we can make the best choices going forward.
I'll try to find the sources and post them on parent.
I’m also unfamiliar with any data to suggest the increase in rates is anything but a change in diagnostic criteria.
And it’s my field, so I’d OP has data to share, I’d be very appreciative of a link.
Right. These are the precise prevalence numbers that have been addressed in multiple studies showing that the change is attributable to increases in public awareness / detection efforts, and broadened diagnostic criteria.
This link talks about prevalence rates. I don't see anything talking about an increase in autism rates that is not just explained by increase in diagnoses as the OP claimed
> Would this mean gene-therapy could potentially undo autism?
Almost certainly not. Autism is caused by developmental changes. This means that any gene therapy would have to start before the embryo development is even finished, i.e. in the mother’s womb. After that, it’s essentially too late. Think of it this way: Could gene therapy make an adult person taller or smaller? Despite the fact that height has a large genetic component the answer is obviously no, since skeletal growth stops after puberty.
> I believe it's now actually agreed upon that autism rates actually ARE increasing
You’re jumping the gun there. It’s plausible that there are factors that are causing an increase of autism rates (e.g. ageing parents) but so far there’s no positive evidence that this is indeed the case, or that diagnostic changes aren’t the sole reason (see https://en.wikipedia.org/wiki/Epidemiology_of_autism#Changes...).
It all depends on whether it is a structural thing that is established during fetal development, which can not be fixed post birth, or whether it is part of the brains's development post birth.
There is a shit ton of brain development post birth -- not structural (the growth of the initial neurons) but in weeding out pathways and reinforcing certain pathways. A lot of it is based on complex feedback between activity, neurochemical releases and receptors. All of that is fair game to change post birth.
Given that autism (like many other psychology labels) is a label for a diverse group of disorders which we can not fully tease apart accurately at this stage, it is likely true that some forms of autism can be treated post-birth, but others will not be.
> Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?
This paper is mostly about the impact of de-novo mutations, i.e mutations that are found only in the child and not in its parents. One theory is that as paternal age is rising and a higher paternal age is linked to a higher number of de-novo mutations which leads to a higher chance of de-novo mutation related genetic diseases like in this case autism (and other mental disorders).
Note that the paternal age in developed countries has been at a historic low in the mid 20th century, which may have lead to a historically low rate of mental disorders in the last decades.
This "older parents" hypothesis is thrown around very often, but it's entirely based on correlational studies (obviously, it wouldn't be ethically possible to do it in a controlled study).
And there's a very plausible alternative explanation for that correlation: Autism is probably at least partly genetic and autism impacts social interaction. It's very plausible to think that it simply takes people with autistic personality traits longer to find a partner to have children.
No, its also based on the fact that older parents (and especially fathers) lead to more de-novo mutations (which you can already see in sperm) and in this study now they show that especially de-novo mutations play a role.
If the older parents hypothesis was not true, you would not find higher autism rate is younger siblings or how do you account for that in your alternative explanation?
But sure, as they say in the paper, its most likely not a single large effect variant that causes autism but usually the combination of multiple rare variants. The genetically inherited part may also play a rule. For a complex disease such as this, its not a single cause that is responsible even for one patient. A tall basketball player can be tall due to some luck, tall parents and good nutrition all at the same time.
> The hypothesis that autism risk in offspring is positively associated with high parental intelligence, and high socioeconomic status, traces to Kanner (1943, p. 248), who stated, referring to autistic children, that “they all come of highly intelligent families,” at high levels of educational, socioeconomic and occupational achievement (Kanner and Lesser, 1958; Rimland, 1964). King (1975) reviewed a set of demographic studies motivated by these findings, and reported strong support for the pattern of high socioeconomic status linked with autism, including support from studies (e.g., Lotter, 1966, 1967) that checked all young children (of 8–10 years) in a given geographic area for infantile autism, and thus should be largely independent of confounding ascertainment or help-seeking biases, variation in access to relevant health care, or variation in parental awareness.
Note that these observations are 60+ years old. Read the entire "Socioeconomic status" section of the paper I cite. They argue the same and state genetic testing should be done to back it up. These seems an ideal study for 23andme (yes, yes, I know how a vocal minority feels about this org).
I guess what I'd like to know is (and I'm specifically asking you because you seem to be knowledgeable):
1. It sounds like de-novo mutations are the best theory for 70%+ of autism cases per this paper, right?
2. Does anybody track the "base rate" of de-novo mutations / generation in humans? If so, how many generations back do we have data for, and how many regions?
3. Aren't we seeing an increase in autism is developed nations even within poor uneducated families with young parents?
One study says ~38 individual base mutations per generation, but that increases by about 2 bases per year of the father's age, which is still not much given 6 billion base pairs in humans. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/) These studies, however, are missing rearrangements and other spontaneous structural changes which might not modify the genes at all but might change their expression or dosage. We don't have enough data yet about structural mutation rates, the technology to assess that at scale and low cost is only coming online now. Not sure about the incident rate, but since the guidelines for reporting have widened so much in the last decade that might mask any ability to really know.
Autism is also hereditary, right? Maybe it has a high enough probability of being passed on through the genes that it is causing the rate to increase over time. It may just be a fluke and we'll see it decrease again over time.
Also note that most of these are spontaneous mutations, and that this paper doesn’t distinguish between correlation and causation.
My take, this shoes that something is broken it the very mechanism of DNA replication, expression, DNA repair and cell differentiation, but somehow we fail to detect those aberrant genes on late stage. So their regulation in the early development stages is when we need to look, but that’s very tough to do.
Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?