Vasopressin deficiency: driver of social impairment and fluid imbalance in ASD? [pdf] | Hacker News Reader

Vasopressin deficiency: driver of social impairment and fluid imbalance in ASD? [pdf]

med.stanford.edu

137 pointsjbotz101 comments

Now that's some serendipitous reading.

I've been on the hunt for possible mechanisms (for further study) as to why last year after trying an SSRI (escitalopram), to treat an anxiety disorder co-morbid to my ASD, that I ended up in the hospital in a hypertensive crisis. Was an all around terrible experience and I hope one day I can figure out WTF happened to me.

Interestingly the BP rise seemed to be mostly diastolic driven and I had crazy excessive urination which made me think about ADH/aldosterone/etc. Seeing ADH is potentially linked to ASD definitely catches my attention! Some of the alternative theories are, I am a MAO-A knockout (unlikely because of lack of intellectual disability), or possess a hyperfunctional SERT (also linked to ASD).

Really excited for the results of the whole genome sequencing I ordered to arrive.

ive been doing my own research for similar reasons (zoloft in my case), although i fortunately did not end up in a hospital. my girlfriend works with autistic children and swears i have ASD but I havent gotten around to being officially diagnosed, nor am i fully convinced of her claim. if you dont mind sharing, what genome sequencing service did you use? granted i havent looked too far but a lot of services i saw were kinda sketchy. hope u find the answers u seek :)

Oh the popular WGS services are a borderline scam. I fell for their BS unfortunately so are out a few hundred euros. I don't expect to see results for 12 months or more (if ever).

In the end I found a local company that does WGS sequencing and they are a lot more reasonable to deal with, maybe 1.5-2x the price. So perhaps look for smaller providers, they are all just reselling time on the same Illumina machines.

In your case, just confirming, your blood pressure is otherwise normal and you experienced an episode of severe hypertension after starting Sertraline (zoloft)? No other contraindicated medications? No indications of a bipolar/mania or something of that nature? I've talked to maybe 3x other people now who've had similar experiences (after scouring the internet), and the only commonality I've found is ASD.

This is a bit of a pet project of mine, so if you want to chat about ASD shenanigans, please reach out to: asd.shenanigans@mailbox.org

Apologies if you've already discounted this, but serotonin syndrome came to mind when I read this.

I was a guinea pig in a clinical trial for a drug that was meant to help with social symptoms of autism, the mechanism of which had something to with vasopressin (I don't know the details): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260643/ .

It didn't do anything for me and the study got cancelled after I'd been taking the drug for some months.

I’ve theorized in my book _Fat Gas_ that vasopressin levels are tied to elevated indoor CO2 levels.

Would not be at all surprised if these novel social conditions stem from not going outside enough and from poorly ventilated buildings (especially gyms and conference rooms) and transport (planes trains and automobiles each routinely exceed 1000 ppm from everybody’s lungs).

Or dense urban housing. But we're not allowed to criticize that, right. Homes with yards and green space are evil!

CO2 levels are high in enclosed spaces, not in urban environments

People who live in urban environments statistically spend less time outdoors.

Citation? Won't people who live in small apartments need to go out more often for necessities? I know I did.

In US cities, going for groceries barely entails time spent outside. You drive your mobile living room to the store and back.

The person I replied was speaking specifically about urban areas.

Did your source consider time spent in vehicles to be "indoors", "outdoors", or its own category? It definitely makes a difference.

Oddly, I've suspected the opposite. In my eyes, people who live in urban areas walk for transportation far more often than suburbanites.

This doesn't follow?

The co2 level indoors is decided far more by whether you have the windows open (or perhaps if you're cooking) than whether you have people living close by to you.

Many high rises in urban areas have few windows that open and poor ventilation for cooking. There is a relationship, although maybe not as large as parent is implying.

Actually, roads and parking garage and driveways take up spaces that could be used for parks and greenery. You could have tramways with grassy cover, for example.

Every time when I drive to anywhere, I am surrounded by five lane stroads.

By removing all these spaces for cars, you could add back in green spaces. Houses with backyards can still exists, but they will be closer together. Parks will be closer and more accessible.

Plus you can design buildings to have green spaces, or at least support plants. Special consideration would be needed to make rooftop of buildings green, especially when you have to consider the weight and wind.

Space efficiency in urbanism is the key to reclaiming green spaces in our urban context.

when did I say anything about cars? I say to hell with all cars, replace everything with bicycles and electric scooters. Then we can use lightrail to connect larger communities to one another.

You’ll have lower CO2 levels in a dense urban housing with windows open, than in a home in the middle of nowhere with the windows closed.

The issue isn’t the higher amount of CO2 in the ambient air in the cities (AIUI it is; marginally; but it doesn’t matter); it’s that CO2 is very good at concentrating in enclosed spaces.

literally only in the currently designed world dominated by large cars, which is equally outrageous. Nuke the entire nonsense system we have, let people have homes in yards, and force everyone to get around on bicycles and electric scooters and electric accessibility carts.

I'm confused; what changes to indoor CO2 levels do you think that would bring?

I mean, it's cars. Fossil fuel combustion in general, but car exhaust in particular.

Cars don't lead to increased indoor CO2 levels.

Yeah, I'm disagreeing with you. It's not CO2. I won't say it's impossible, but it's pretty implausible. We already know how bad leaded gasoline was at poisoning an entire generation. Modern cars are cleaner, but miles driven keeps increasing and the amount pollutants being emitted are poisoning people.

So cars=bad∴cars->ASD? Is that your argument?

How would this be true for planes? They're constantly being fed fresh air from the engines during flight.

It's true for every other mode of transport but objectively false for planes in flight. However, I'd be curious to see the average when including time sitting on the ground, taxiing, etc., and how that much lower speed affects circulation.

The refreshed air in the cabin is driven by engine bleed air (or a dedicated pressure pump) so even at idle power there is nothing preventing a high rate of cabin air exchange. There might still be less air flowing on the ground due to 0 cabin air pressure differential, but speed of the plane isn't a relevant factor.

I carried a CO2 meter on a flight recently, to use CO2 as a proxy for COVID risk. The levels were quite high for the whole flight--over 1000 pretty much the whole time iirc and worse on the tarmac.

How did you calibrate the meter for the changing temperature and pressure? Most CO2 meter designs are extremely sensitive to pressure changes.

It's a cheap portable, with no calibration possible. I have no idea what effect pressure would have on it, unfortunately.

Could you elaborate on what you mean by "novel social conditions"?

ASD diagnoses have skyrocketed in the past few decades (years?) with no clear cause. I'm just old enough to remember a childhood without cell phones - we didn't have a computer in my house until middle school but we were lower income than most of my friends - and people are definitely inside more and outside less than they were when I was 8 or 9 years old.

It seems like a plausible theory.

Lots of other things have changed, including, people are having kids older (known correlate), the DSM definition changed, and the general awareness has radically increased.

I've always understood the increase in diagnoses to be more about increased awareness than about a change in human behavior.

E.g. it looks like autism wasn't defined as a spectrum in the DSM until either 1994 or 2000: https://www.spectrumnews.org/news/evolution-autism-diagnosis....

When left handedness was seen as a disorder and students who used their left hand were beaten, rates of this disorder were a few percent. When the idea of left handedness became mainstream, rates skyrocketed and we know the base rate is about 10%.

Homosexuality was considered a disorder in the DSM until 1974. Self-reported rates of homosexuality have skyrocketed since then. Most likely explanation is that the true base rate has not changed, just society's measurement of it.

Children with ASD in prior generations were labeled as delinquent, troublemakers, retarded, or were abandoned by their parents and communities.

You think. Let's be clear about what's a hypothesis vs. a confirmed fact.

I wrote a response that argues against your hypothesis, and then I realized ... "do I really know what I'm saying? Or are these my preconceptions and biases?"

> and we know the base rate is about 10%.

Sinister.

I think it would be cool to be left-handed in a country where the language is written from right to left.

> Sinister.

A dexterous response, to be sure. ;)

I find it interesting that the rates of a whole bunch of these uncommon-but-still-prevalent differences seem to cluster around 10%. I can't help wondering if it stems from prehistoric humans living in small group of 20-30, so each band would have on average 2-4 of each, giving the group a wider range of capabilities than they would otherwise have.

Something influenced by 2 double recessive genes will occur ~1/8 of the time in a population where the recessive gene is common.

It doesn't seem plausible to me, based on my anecdotal experience with an ASD child who played in the woods all the time.

Correlation, as the saying goes, does not prove causation.

When I was younger autism wasn't called autism - it was blamed on mothers who worked, "refrigerator mums". Doesn't change the fact that I'm autistic though.

Vasopressin is tied to single-cell acid/base regulation, on that chromosome 3/7/17/X major axis.

This makes a LOT of sense explaining how wearing a mask throughout the day observably changes behavior!!

If elevated CO2 increases vasopressin, and if increased vasopressin drives symptoms of autism, then wouldn't we see a large population with autism symptoms in the Midwest or anywhere that people are indoors all winter?

I think it's vasopressin deficiency that is claimed to drive those symptoms.

My nephew is on the spectrum (fairly severely). His mother and father are obsessed with air quality and used filtration and forced ERVs for the entire pregnancy and upbringing. Please do not make such strong medical claims without any scientific backing, it is quite harmful to kids with autism and their parents who are already overwhelmed with quackery.

the guy wrote a book on it. so far his evidence far exceeds yours, which is none.

I can write a book on anything and still have no evidence or idea what I'm talking about.

Can't tell if this is sarcasm or not...

its not. the value of the story of his nephew is a stark zero in terms of providing any kind of valuable information into the conversation.

Saying "I wrote in my book that..." is basically the same value, in the absence of further information. We don't know how qualified the author is to make such claims, what the motive behind writing the book was, what sources they used, and so on. Even if you read the book, you might not satisfactorily find that information, or sources may themselves be misrepresented. Anyone can write and publish a book these days, making any claim, misinterpreting data, wilfully or otherwise.

If the person you replied to wrote their anecdote about their nephew in a book, would you find it credible then?

With respect, this does not sound rooted in factual basis. Anyone who has taken physiology and been educated in anesthesia knows that there are numerous factors and feedback loops that decouple your theory of a direct link between ambient pCO2 and "vasopressin levels".

I'd like to hear a more detailed explanation on how you feel it overrides compensatory mechanisms in ventilation, with subsequent breakdown in metabolic compensation of acidemia, and how you override negative feedback loops in the RAAS system including inhibition of ANP excretion, unless you theorize it is blunted at the renal level and natriuresis becomes down regulated in this scenario.

Or basically if you want to reframe how everyone sitting in a house has subclinical SIADH I would be eager to hear a more detailed explanation.

That’s a fascinating introduction - they are concerned that dual (!) name of the molecule might be hiding all of its functions!

It looks like naming thing is not just a problem for programmers.

When I was diagnosed with a neurological condition that was having mostly physical symptoms, the first-line defense was antidepressants. So-named because they were developed to relieve depression, but really what they do is inhibit absorption of serotonin and/or norepinephrine leaving more free in the body to act on myriad different bodily functions. In my case, it actually caused serious digestion issues. It really clicked for me how everything in your brain is a physical process. Not just motor function, but cognition and emotions are all physical functions of how a very complicated mess of molecules bounce off each other. Autism, Alzheimers, ALS are all just misfiring molecules inside your skull. And it is therefore a given that it is physically possible to realign them back into order somehow. We just need to find the right tool to do it.

Yes! This! We are our bodies, and our bodies are biochemical. I'm encouraged by growing awareness and acceptance of things like psilocybin-based treatment for PTSD. Psychobiology is fundamental to... everything a human can experience or be.

Of course there will be lots of molecules involved, but that doesn't make it any easier to understand let alone do something about it. In medicine and especially in psychology our functioning is a huge black box with only indirect knowledge about interactions with certain things at a very high level.

Was an anti- inflammatory diet for me

Doing quick search, there is also interactions between Vasopressin and salt and blood pressure. Could ASD be helped by reducing salt? or increasing salt?

I'm not knowledgeable enough to untangle all of the studies where these terms are also used, which I guess is part of the problem this paper is pointing out, that the terminology/naming is confusing.

Is this saying if you have blood pressure problems you might also be at risk of ASD.

Or opposite, if you have ASD, you might have more risk of blood pressure problems.

"The name AVP refers to the hormone’s role in increasing vascular resistance and regulating blood pressure (via AVP receptor"

"Given the emerging evidence for central AVP signaling abnormalities in ASD, we would expect individuals with ASD, or a subgroup of them, to be at increased risk of AVP-related medical conditions and symptoms. "

The article is proposing the latter. Low AVP could contribute to symptoms of ASD. If this is true, they expect a positive correlation between ASD and other better-known issues caused by low AVP.

You’re almost there. It’s saying that you’re at risk for central diabetes insipidus known to cause abnormal thirst and urination in like the next paragraph.

What I find hilarious is that the whole first paragraph is about things being named after scientists and then there’s an author named Gesundheit…now I need to look that up.

(Gesundheit = Health)

Sometimes, and sometimes it’s a name.

https://profiles.stanford.edu/neil-gesundheit

And very occasionally it's a serendipitous name!

Nominative Determinism is a hell of a thing.

...and so is Selection Bias.

One thing I always found interesting is that inducing a fever in autistic people, in some of them it will reduce the severity of their autistic characteristics.

citation.

Google. https://hms.harvard.edu/news/cracking-fever-autism-mystery

Your citation looks fine, but telling people to Google for citations is just pointing them straight at spam.

"...in mice."

Confirmed in mice, observed first anecdotally in children with autism.

I'm blown away we still as a society don't have a system where all of this information is quickly accessible in a sorted way by various trusted organizations that follow specific protocols that people determine how trustworthy they are.

That would require us as a society to develop concrete solutions to determining who can be trusted. That’s obviously impossible, so we’re stuck with the process we have.

It's actually the individual's responsibility to develop an understanding of how one determines what is trustworthy and what isn't trustworthy, and they they do their best to develop that. For example, if someone lies, they are caught lying, the evidence is presented but a person doesn't care or put any weight on that someone lied - well, they are going to rank that person or an organization they are running or still party to.

I'd argue it's bad actors who don't want such a highly organized system that helps people discern easier, a sort of societal wide "fog of war" to make knowing closer towards the truth, the whole truth, and nothing but the truth - harder; with AI generated images and video coming, I don't know how society will cope with such a thing - where "video evidence" could exist painting a horrific reputation of someone to destroy them perhaps not only economically but perhaps also weaponizing a mob to kill someone.

you mean like the "science" and "experts" paid off by the sugar industry to promote sugar for 50 years while demonizing fat?

Who was promoting sugar, exactly? This is an extraordinary claim that requires extraordinary proof.

The one that weirds me out is that sleep deprivation can quite rapidly reduce depression, if only temporarily:

https://www.pennmedicine.org/news/news-releases/2017/septemb...

I did this in my late young years. It worked. Got started reading into “polyphasic sleeping “ , we were deluded for thinking it could be a long term healthy schedule but it definitely seems to have given me a mood reset and cured my insomnia.

Some of them also respond to anti biotics

> Could ASD be helped by reducing salt? or increasing salt?

Personal story here (N=1, not claiming anything other than that). My dad is clearly ASD, and has battled high blood pressure for as long as I can remember. He's now suffering the consequences of 40 years of absolute salt avoidance. 1) I never saw and reduction in the ASD over the past 40 years, 2) lack of salt never changed his blood pressure, and 3) now he's suffering other heath effects, but won't listen to me and only wants to do more of the same.

Avoiding table salt thoroughly could potentially lead to iodine deficiency. It was somewhat common in the past so most table salt over the past century has had iodine added to it to avoid this, but it's cropping back up a bit as people avoid salt or prefer to use "natural rock salts" common in fine cuisine, which are not reinforced with iodine.

Iodine is in a lot of foods.

If it were common enough in available foods then they wouldn't have added it to table salt.

IIRC this was added long ago, when Americans ate less meat, dairy, and seafood and were more prone to malnutrition.

And yet, levels have been measurably going down, and Europeans are already fairly deficient since they don't have as many iodine supplementation programs:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459956/

https://www.cdc.gov/nchs/data/hestat/iodine.htm

My prediction: in fifty years, "low-salt" will have gone the way of "low-fat." Too late for millions of people whose health was injured and lives shortened by these terrible fads.

Improbable since reducing added fats is still as good advice today as it was 5 decades ago.

Exactly right. Reducing dietary fats is "as good" advice as it was or ever will be.

I'm sure you are responding with good intentions, that some 'healthy' fats are needed in a healthy diet.

The demonization of fat is wrong.

But Also

Eating 5lbs of Ribs every day and weighing 300 lbs is not healthy.

Same with salt.

The 'healthy' amount of salt is a U curve. You can have too little, and too much.

It's just in the typical American diet, there is so much Fat and so much Salt, that most people area already at the extreme of the U curve and should probably start cutting back.

> Eating 5lbs of Ribs every day and weighing 300 lbs is not healthy.

If you started at normal weight and ate 5lbs of ribs (or, till satiety) every day, with as much butter as you'd like, but ZERO carbs or artificial sweeteners, you'd never gain weight, much less get to 300 lbs. That's my point.

But don't believe me - this experiment has been done many times.

Google: "zero carb" or "Banting diet."

"or, till satiety"

That is the key.

You can eat vegetables until satiety and also not gain weight.

Banting seems to be about non-processed whole foods. So guess I'm doing that.

My point was more, there is a group that goes 'zero carb' and eat really unhealthily. They take it as a license to pile on the ribs. Not that 'zero carb' by itself is unhealthy.

You'll probably say cholesterol is also ok. But plaque buildup does lead to hearth attack's.

"Unfortunately, emerging research shows that a ketogenic diet actually increases the risk of cardiovascular disease. In a young, fit population of CrossFit athletes, following a keto diet for 12 weeks led to an average weight loss of 6 pounds but increased “bad cholesterol” (LDL-C) by a whopping 35%.

Typically, you would expect to see LDL-C levels drop when you lose weight. LDL-C has long been associated with cardiovascular risk because it forms arterial plaques (a cholesterol build-up in the inner lining of arteries), and emerging research that followed people for 12 years has now directly linked long-term ketogenic"

https://sitn.hms.harvard.edu/flash/2023/keto-its-probably-no....

His BP could be worse with salt.

Oh, huh, I have always noted an odd ruddiness/doughiness as being common to certain ASD individuals I know. I always just attributed it to being overweight etc but I wonder if that’s the vasopressin fluid imbalance.

You can get tested for this if you have ASD by getting a copeptin test.

What do you change about your lifestyle with that test result? I have a child with ASD, and also drinks mad amounts of water. But I didn't see any treatment plan if this deficiency is confirmed.

Usually the treatment is desmopressin I believe.

Find a clinical trial, perhaps? There seems to be a bit of study in this direction:

https://med.stanford.edu/news/all-news/2019/05/hormone-reduc...

Thank you for this link!

Essentially if this theory is accurate it kind of shares similar patterns to diabetes insipidus which is essentially vasopressin dysfunction.

So you can Google that and see how that is treated and tested for.

Thanks

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