For convenience here’s the paper: Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions by Duarte, Pain, Bendall & others: https://www.nature.com/articles/s41467-024-48153-z
(Kudos to the medicalxpress writer for actually linking to the paper.)
It seems to be quite readable. Just go fast enough to hydroplane on the surface, and jump as usual between the abstract, conclusion, abstract again, the middle part, the introduction and then put it away and sleep on it and come back to it and hydroplane and jump and… you know, all of that. Paper reading.
Before reading, in the headline I sort of saw the question whether embedded viral DNA might be getting “deployed into prod” and causing bad stuff to happen. The second ha-ha-contrarian-I-am-very-intelligent thought—also cheap to produce—was whether the ability to survive a viral onslaught brutal enough for the virus to embed itself in its quarry might be an indication that ancestral individuals had a more robust and aggressive immune system than peers who didn’t survive to reproduce. And if this could show up as a runaway inflammatory response in the current era. (From what I understand, psychiatric disorders are very very often accompanied by neuroinflammation. Practically… always?)
Such a great paper! I can speculate all this before I’ve even read the thing!!
Very interesting. The paper suggests though that for many of these it's unlikely it's due to an immune response:
> It is not clear yet how the expression of the high confidence risk HERVs may play a role in psychiatric disorders. It was previously hypothesised that differential HERV expression in psychiatric cases was likely to be a by-product of immune responses against current or past infections34. Indeed, HERV expression is modulated by exposure to several pathogens35,36 and can activate inflammatory cascades37. This is an interesting theory that corroborates the fact that individuals with psychiatric disorders typically have higher incidences of infections38,39,40. However, our main analysis found that 1238 HERVs expressed in the brain are regulated in cis, some of which in association with risk for complex psychiatric traits. This indicates that there are HERV expression mechanisms directly contributing to disorder aetiology, that are not simply part of compensatory responses, or triggered by environmental factors.
Thank you! To me, this is a great example of how to read papers. I think I skimmed that section a couple of times after writing the comment and it didn’t register.
Thank you for your honest perspective! Sincere thanks. I guess it’s the approach of 45 years of age that I am unfazed.
I’ve heard a number of
times that my persona in writing absolutely does not make sense to some people – until they meet me.
I think I can assure you of my non-arrogance. The wry, cynical, even flippant? note is directed at myself. My limitations and recklessness and jumping to conclusions.
If you find me, I offer you a cup of coffee. In return I’d like an equally honest reassessment.
(Full sincerity here!)
edit;
Ah. Also. Another thing I can assure you of: Sometimes, afterwards, I come across my own writing and find it awful. in exactly that way. Like an annoying and arrogant 15yo had written it. Which is my greatest fear. To become that 15yo again, the person I certainly was for a decade or so. (Starting at around age 12-ish.) I knew I was annoying but I didn’t know I was arrogant. It turns out the two were related.
IMO there has been a growing undercurrent, in online discussions forums, of disdain for writing and authors who aren’t well-established as authority figures or known experts in their field. Tone and word choice is narrowing into a conversational style, and anyone “straying from the pack” sticks out like a sore thumb in online boards.
Anything sarcastic or playful can be perceived as insincere.
I’d be happy to read more of your thoughts—you should keep writing.
You should just leave it at "people like different things" instead of making claims about why people don't like something (especially something that you like).
Because now you invite more negativity (on top of the original negativity and now yours) as people who didn't like their writing may now want to defend themself because they just didn't like the style and aren't part of some "growing undercurrent" who can't appreciate his brilliance because he's not "well-established nor a known expert".
Maybe they just think the writing is overwrought like when you outgrow John Scalzi's lamewad writing after briefly finding it clever in Old Man's War? (I think that's a decent place to end this because Scalzi is a very successful author.)
The problem is, even smart 15 year olds with fresh takes have to learn that no matter how interesting their ideas are, the scientific establishment is much more focused on finding good evidence to support incremental discoveries, rather than wide-eyed speculation about how complex biological processes work.
(I was that 15 year old, and then after many years of sciencing, realized that it was nothing like what I thought, and that all my best ideas were either wrong, ahead of their time, or stolen by more accomplished scientists.
...and why not encourage to keep being like the 15 year old instead of accepting the status quo?
The only problem i see here is, apparently this "establishment" got to you faster than you could remind yourself of what's truly important to you.
I hate when people get discouraged by other people who mostly don't care that much & are afraid... they feed on your Neugier. Don't feed them. Feed other minds alike & screw the establishment.
becase when the 15 year old grows up, unless they are an absolute true genius (and even then), if they try to go around chasing wild ideas, they won't get funding or the ability to run the experiments to build a case for their hypothesis.
I find your harshness, in response to a purely positive and informative comment, to be terribly arrogant and annoying, like someone pretending to be as smart as a smart 15 year old.
I always think when people react so negatively on text (comments, articles, blog-posts), they reveal a lot about themselves.
Not in the sense of a "moral high-ground" type of argument that is usually aimed for with this phrasing.
Rather: To be so convinced about knowing how a text must have been meant or what the author must have thought that one writes a very absolute judgmental statement, the reactor is most likely either very narrow-minded and isn't capable of dealing with thoughts that are not the first to salute ones mind, or, they reveal that in their mind their proposed "intention" or background is the truth, because they themselves would have only written a similar text with that intention or background... so either way: people being so negative (especially to strangers on the internet) about positive things, for no reason & without being asked, are just full of... themselves... (like me, i mean who am i to ramble this irrelevant stuff).
(I was about to delete it again, as i usually do after writing things down & then realizing they're stupid or not polished enough to convey the idea, but hey, i am also just a 15-year old arrogant mind that already wasted his time... so now, that you are here, i successfully also wasted yours. Your welcome!)
This kind of science leaves me with lots and lots of questions.
E.g.: As our understanding of DNA progresses, and we link more and more of it to different traits, will we eventually get into a situation where a swab on the water glass tells potential employer much more than the interview?
Or: imagine that in addition to the discovery "viral DNA in the human genome linked to major psychiatric disorders" there's a discovery that "this viral DNA is much more prevalent in [a certain population]". What will be the consequences of this?
> E.g.: As our understanding of DNA progresses, and we link more and more of it to different traits, will we eventually get into a situation where a swab on the water glass tells potential employer much more than the interview?
For almost anything that an interview is designed to discover: no. DNA manipulates probabilities of certain things in one direction or another, but then that probability shift is amplified and attenuated through layer after layer of immensely chaotic biological, then psychological, then social processes.
The connection between genetic code and "things we care about" is extremely finicky, with the exceptions being certain types of diseases which emerge much closer to the genetic code than any sort of social behaviors do.
Once we get past the diseases research, what's stopping us from going further? Could we discover e.g. a DNA sequence in human genome "linked" to higher intelligence, or better leadership qualities? And if yes, what can guarantee that instead of the Nazis' "master race" based on pseudo-scientific scull measurements we won't discover "master genes" based on actual DNA science?
What frightens me is not what we can discover, it's what we as human society will do with that information once we discover it.
Because DNA won't tell you whether the genetically-genius person smashed their head on a rock and is now totally unfit for your high-paying engineering job.
Nor will it tell you whether the genetically-average intelligence person spent 14 hours per day for the last 8 years in the code mines building awesome stuff.
I.e. it won't tell you the types of things that interviews are designed to suss out.
Any test mixes signal with noise (Maybe that superstar candidate is just awful at interviews? Maybe the super lazy coder puts their laziness aside only for the interview day?)
Combining many noisy factors into one, with the correct weighting, will always, on average, give better results than a single test.
That means that as soon as DNA tests give even a weak prediction of 'iq' or 'leadership abilities', companies will integrate them into hiring processes if legal and cheap.
I think we're past that. Setting aside politically hot topics like IQ, Height is genetically determined and makes a huge difference in life outcomes. Now it's all about what we do with that information.
That makes height an easy topic to talk about, but it's still challenging to think through the implications. If you can increase your child's height by 20% and thereby increase their likely income by 25% - is it morally right not to? Does it matter whether others can afford that intervention? Is it morally right not to fund public access to such interventions? Does the answer change if relative height is all that matters?
If there were single genes that produced high intelligence scientists probably would have found one by now. Those sorts of traits are almost certainly highly polygenic. Any single gene is likely to have both small and unpredictable contributions to the traits in question. Even totting up all your "good" and "bad" genes to try to come up with a genetic score is fraught due to complicated interactions; perhaps two "good" genes interact badly and make a bad result, or similar.
I mean, read up on the history of eugenics. Mainstream establishment science has come up close to doing exactly this sort of thing in the past (including sterilizing people who were considered "unfit").
It seems almost certain that we will continue to find more DNA sequences that are correlated with increased intelligence.
> where a swab on the water glass tells potential employer much more than the interview?
More likely RNA, because DNA doesn't mean traits are actually active. Also, only if you believe nature>>nurture and that experience doesn't matter. The level of understanding of your issues and how to counteract them makes a difference too.
In practice you probably want someone with issues they know how to cope with and lots of enthusiasm for $job rather than a rando with great generic potential and hating every minute at work.
Imagine a situation where there are two presidential candidates, who are both somewhat bad, and then it becomes a matter of public knowledge that one of them has "Viral DNA in [his] genome linked to major psychiatric disorders". I don't think what I do or don't believe would matter in the larger scheme of things.
The assumption is that they're comparable with nothing that makes one stand out ("both somewhat bad"). In that case, sure, it could mean something. But you rarely see that situation, because it doesn't make sense to run against someone not very different from you.
I guess on the DNA level there is not much difference between any two candidates for any $job ... yet. The questions I'm asking are not about the current situation, they are about potential (not yet existing) situations we can find ourselves in with the advancement of DNA science.
Well, in the US at least, if the presidential candidate is well supported by their establishment party, it seems like there would be little-to-no difference. (much like my voting activity in first-past-the-post systems)
I think we already know that, it's just there's usually a tradeoff for these things. Subgroups with higher average IQs also have higher rates of psychiatric disorders etc... If society's healthy there'll be lots of opportunities for subgroups to niche down. If it's not, everyone will be chasing the same rabbit and the inherent unfairness is going to compound that problem.
Amateur question: if we've retained these ostensibly dangerous or at least deleterious viral codes in our DNA, is there any reason why these virii don't serve a important evolutionary or remedial (maybe crisis) purpose?
Many important figures of history have had these traits. That isn’t to say that they are good in the whole, only that it is not obvious that they are something so maladaptive that they get trimmed from the evolutionary tree.
It’s only in the last 150 or so years that we expect all people to be Rational Economic Agents. If anything, I think /that/ is something that will get trimmed pretty quickly from the tree…
Ancient population suffers from massive viral load, causing such catastrophic damage that the whole surviving population carries some of the viral DNA fragments with it to this day.
Various illnesses are caused by promoter genes. These are genes that serve no purpose but they specialize in promoting themselves, so they spread through a population even though they serve no evolutionary fitness goal (often they bring illness). A good book on that topic:
Genes in Conflict: The Biology of Selfish Genetic Elements
However, referring to the original article of this thread, it is also possible that the same genes that give us depression also give us something positive, such as creativity.
There are perfectly plausible reasons why the conditions we regard as mental illness are adaptations that help evolutionary fitness:
- Depression puts one into a low-energy, contemplative state that enables reflection, healing and formulation of reformed ways of thinking and being ("dark night of the soul");
- Bipiolar is a pattern of swinging between high-energy bursts of inspiration and creation, and low-energy states of recuperation and reflection;
- Schizophrenia is a way of disassociating from real-world experiences that are too painful to experience with normal consciousness, and is a preferable alternative (from an evolutionary perspective) to suicide, buying time for processing and healing to take place, given the right kind of support.
Of course, that could be seen as a "just so" story too. Except that evolutionary theory says that only genes that promote evolutionary fitness should survive and spread through the genome, particularly given that replication of any given gene carries a significant cost. We can also easily observe that conditions like depression and schizophrenia normally develop in response to a trigger - i.e., a traumatic life event or extended period of abuse.
So, it's far less of a confected story to just accept that these conditions have been retained in the genome for the reason that makes most sense according to evolutionary theory: it's evolutionarily beneficial for them to be there.
First, I don’t know why you feel the need to include a hostile ad hom barb like “You seem to think evolutionary theory came to an end in 1882”.
I’ve done multiple Google searches and even done Google Books searches in the very book you linked, for the exact phrase “promoter gene”, and it really doesn’t seem to be a term that’s used, at all, really.
DNA promoters are well recognized, but not in the context you’re talking about.
I can very much understand the notion that genes may act to further their own propagation at the cost of the host’s fitness - sure.
It’s just that we first need to see evidence that it’s happening, by having a clear definition of what favours vs costs the host’s fitness.
The hypothesis you’ve cited (and from the book reviews it seems even the authors concede their hypotheses are highly speculative), seems to start with the assumption that these mental illness traits are opposed to the host’s fitness and confer no benefits whatsoever.
But all we have to do is point out the many cases in which these traits actually do benefit the host, which I did and you even conceded in the last line of your comment, and the hypothesis is void.
It reminds me of the “junk DNA” hypothesis, where researchers couldn’t find an obvious use for large sections of the genome so just assumed it to be useless and called it “junk”, only to be later found to have very important roles:
A common evolutionarily explanation for the existence of depression in the case of an illness is that it forces the individual to take rest, and being withdrawn lowers the risk of transmitting an infection. How depression and inflammation are related is quite well documented.
I read somewhere that hunters who hide in one place and need to stay focused for several hours of the day, have an advantage of being schizophrenic to a degree
Or hyper-focused with ADHD traits. Counter-intuitively hyper-focus on tasks "interesting" to the patient is an ADHD trait, it is not just being a "space cadet".
Men who were prone to alternative/extreme states of consciousness would have been better able to summon up the wild emotions necessary for savagery and violence, making them better fighters and hence giving them better mating prospects.
They would be constantly vigilant and unpredictable to someone unfamiliar with that particular trait. When wandering you might only have yourself as a reference so they would be a counter to that
If they've even lived long enough, no absolutely not. Unless you think someone who is routinely depressed is 'vigilant'.
[Hypo]mania is not the primary state of a bipolar patient. Can't speak to schizophrenia, but for those I've seen with that illness, functioning isn't their primary state, either.
Mania, maybe, but not depression. It clouds the mind and saps motivation in a way that would undermine efficacy in both hunting and surprise encounters.
Obviously I don't think it can be turned on-off, why would you even think that I was suggesting that? It's just easy for me to imagine these scenarios triggering mania in me whether I wanted it to or not, and I don't think I'm that unusual, that's all.
No, that's not how [hypo]mania works. You can 'imagine' all you want, but thinking that a specific scenario or time is when [hypo]mania 'lights up' is flat out incorrect.
And someone who experiences mania indicates an uncontrolled illness. Depression and mania prevent normal functioning. You seem to believe an unmedicated bipolar individual is a functional individual with some inkling of rational thought that could 'go into battle with no fear'.
If you don't know, don't post. And you don't know.
Your statements about what you know about me and my lived experiences, and my level of knowledge of those experiences, is bizarrely cruel. Please do not do this. Please don't try to silence me just because those things don't match up with your own experiences.
I don't know where you are getting the notion that I am saying that mania is rational or controllable. I was speculating based on personal experience around high stress situations. I do not understand why you are choosing to attack the notion that there could be evolutionarily advantageous benefits conferred upon the group.
Edit: we agree that I am speculating. I disagree with you that I have no right to speculate
I know both pretty well, indirectly or not. Given how much they can influence your energy and "will to live" I don't think they'd pair well with having to fight for your life.
Someone with a better grasp of the scientific method perhaps you can answer this.
I am under the impression we (science) hasn't definitively determined causation for depression. How can you definitively determine a link without knowing the underlying causes. It would imply you know how it works, doesn't it?
> Someone with a better grasp of the scientific method perhaps you can answer this.
As a (recovered, former) neurobio phd it seems the "grasp" is mostly there + the clarity you want just doesn't exist here
I.e., the concept of "depression" is pretty hard to nail down quantitatively in the first place: The best model we've got is a kind of self-contained proven-by-internal-self-consistency thing bootstrapped from questionnaires, which is of course further abstracted away onto those model systems we're allowed to kill: For example, calling "how long do mice swim before giving up if you chuck them into a tank of water" is roughly equated to "amount of depression" (this is oversimplified a bit; you correlate a bunch of those measures etc. but still a lot of very weak signals). Even "relevant quantitative data" like fMRI / ECoG is bootstrapped from questionnaires when it's something undefinable like "depression"
Which isn't the end of the world, everything started out like this, it just sucks when people take these results too seriously or infer too much from them.
And even the human black-box stuff in the DSM manuals admits a lot of different subtypes, lots of different and sometimes opposite symptom clusters, etc. It is entirely possible that mechanistically "depression" is a diverse group of mechanisms all boxed up into the most familiar mainstream concept/word.
> For example, calling "how long do mice swim before giving up if you chuck them into a tank of water" is roughly equated to "amount of depression" (this is oversimplified a bit; you correlate a bunch of those measures etc. but still a lot of very weak signals).
Do I understand this? A purely reductionist view of my understanding: this is quantified as "the amount of will to live"? If my understanding is proper, how do you measure this without killing people? I grok that it is an extreme example, I am attempting to glean applicability of such an experiment to humans.
> And even the human black-box stuff in the DSM manuals admits a lot of different subtypes, lots of different and sometimes opposite symptom clusters, etc. It is entirely possible that mechanistically "depression" is a diverse group of mechanisms all boxed up into the most familiar mainstream concept/word.
Totally unrelated, but wife is an LCSW and I've glanced at the DSM. I've become convinced that book is near entirely for insurance purposes, similar to the ICD-10.
ICD-10: W220.2XD: Walked into lamppost, subsequent encounter.
> Do I understand this? A purely reductionist view of my understanding: this is quantified as "the amount of will to live"? If my understanding is proper, how do you measure this without killing people? I grok that it is an extreme example, I am attempting to glean applicability of such an experiment to humans.
I mean in this is one model and typically a "result" means several models are all consistent with the researcher's mental model of the thing. But yes, the forced swim test is one measure of "will to live" and it's treated as that because of similarities to "that which we call 'depression'" or whatever
It is better than nothing, unless one takes it too seriously.
The SNPs can be found in the supplement, so you could check this. But why? Probably it would make more sense to check all risk alleles known to be associated with e.g. bipolar disorder to test for your own risk.
Maybe someone can provide a better understanding, I'm a clinical psych doctoral student, but this is outside my area of research + methods.
On very quick review, it looks like there are is significant association between HERV genetic factors and specific diagnoses given PIP. However, what's not clear to me is effect size or correlation coefficient.
I'm not sure if I'm missing this or it's not reports. There might be a relationship, but at a very small percentage.
Where are the religious people admitting they were wrong? I was told god’s will existed, but here we see it doesn’t? Care to explain/apolgize? This is free speech.
Just for fun - does this sound like what the remnants of ancient genetic engineering experiments on primates to increase their intelligence might look like to anyone else?
This embedded viral DNA would presumably make all cells more susceptible to similar real viruses, since the MHC class I signalling methods couldn't be used to find them.
We can't (currently) cut them out because there's too many cells and they're brain cells. But if we could make complementary RNA, that could potentially neutralize them.
A gene-editing inquisition against anything viral could definitely go too far. For example, we already know of syncytin [0], a protein essential for normal reproduction (placental formation) which is encoded by an ancient proviral genes.
Let's imagine some antiviral inquisitors who are either ignorant of that fact, or else operate in a world where there are very similar genes that haven't been discovered.
If they were editing gametes/embryos, they'd probably discover the problem quite quickly, and either make an exception or abandon their work.
However if they were enacting some kind of retroviral edit on adults (which would be kinda-hypocritical) then things might look fine for a little bit... until someone realizes that there are no more babies anymore and the population is going to go extinct without a fix.
Would it be possible to consider them separately though? Like maybe it will turn out that say 10% of them are beneficial, 65% of them are neutral (either they do nothing at all or a mixture of benefit and harm), and 25% are slightly bad for us (can't be too harmful or we would have already known ig).
Delivering gene therapies into brain cells is a non-trivial task. Also, there's alternatives to cutting the original sequence out; you can also dampen the transcribed RNA with downstream therapies.
'Bad' is notoriously hard to figure out. It might be good for the group to have a few people with major psychiatric disorders even if it's not ideal for that individual or the people who have to directly interact with them.
I love humans, we discover a new interesting thing, think we're big boys who understand everything there is to understand and that we can shape things to our will with no adverse consequences
That's how we got asbestos in walls, lead in gas/paint, freon, pfas, &c. The same story over and over and over again. But sure go ahead and start slicing our dna, what could possibly go wrong?
That's also how we got fire, stone tools, agriculture, microprocessors, vitamins, hospitals that were more than just places to go die... and the very computer network you're using to post.
The Holocene extinction was started when pointed sticks were state of the art and we ate most megafauna to extinction. It would be more the Anthropocene to blame if anything. Blaming high technology is thus rather anachronistic.
Personally I'm of the opinion that the world was already on fire as it were, what with the mass extinctions caused when we became an invasive species out of Africa. If we were still stuck in the stone age like our predecessors we would still be an ongoing mass-extinction. There is some hope to eventually not be an ongoing mass extinction but that would require some combination of even better technology and the right priorities.
As another commenter pointed out, the expression of these genes doesn't cause inflammation. So, maybe the antivaxxers will ignore it, as it doesn't fit well enough into their existing framework.
If antivaxxers held themselves to a consistent model, they would be gone by now. For instance, long ago it used to be about the mercury based preservative that's basically never used now, but somehow vaccines are still evil somehow. Some other way, for sure. They've just got "vaccine = bad" stuck in their head and they'll grab any scrap of info that confirms their bias.
Clearly making fun of my own situation struck a cord with folks. I'm sorry, that wasn't my intent.
I'm making light of my own situation. That's where I am in my own healing journey. This commnet is about me, my experiences, and my father. It is not a suggestion of what your father may have been like. If your father is great, great!
Many people diagnosed with severe mental illness, like my brother, have excellent upbringings including a great father. What are you trying to achieve bybsaying this? You sound ignorant and antagonistic to vulnerable people.
My comment relates to my own experiences. I use humor as a coping mechanism. I'm sorry your brother is struggling, I'm happy to hear he has a great support system, and I hope he finds a treatment plan that works for him.
Also, as much as this comment might strike a cord with people, there is a great deal of truth to it. Just as there is a great deal of truth to your brother's experience. Attachment trauma is real. Trauma related to a primary attachment figure is a real source of pain for people.
Depression is fundamentally different than being sad about things. Trauma can trigger it, but not by merely being sad.
That's the whole point of antidepressant medication. It alleviates symptoms in someone who is sick, but otherwise has no effect on someone who is healthy.
I'll rephrase - CBT has the same impact on the brain as antidepressants when they work, after only 3 months.
And of course you have to follow through. No treatment work without follow through.
I'm glad you found an SSRI that works for you. It's great when that happens. That said, being on the wrong SSRI can cost a life. Being that they are effective as often as they are ineffective, they need to be perscribed with care. Care that is not taken.
Long term treatment plans should centre around psychotherapy. SSRIs can offer some assistance, but again, the risks are too high and people end up on them for far too long. If you want to change your brain, it takes focused intentional work. Therapy is great for that.
I'm sorry that happened to you. I can't speak for all bipolar alcoholics, but I sought treatment and now I've made amends with my son and we have a good relationship if that helps at all.
Both. Sure we make huge progress in depression research and brain research in general, but there are so many environmental things happening, like yours for example, so just saying "oh yeah depression comes from that DNA" or "yeah that's just from your trauma. A lil therapy will heal everything" is just a bit short sigthed. So yeah, just saying that it's all very complex and we shouldn't really try to reduce this beast of a disease down to anything, because everyone has a different story. In the end I was just a little sarcastic, sorry
DOI: https://doi.org/10.1038/s41467-024-48153-z
Open-access PDF.
(Kudos to the medicalxpress writer for actually linking to the paper.)
It seems to be quite readable. Just go fast enough to hydroplane on the surface, and jump as usual between the abstract, conclusion, abstract again, the middle part, the introduction and then put it away and sleep on it and come back to it and hydroplane and jump and… you know, all of that. Paper reading.
Before reading, in the headline I sort of saw the question whether embedded viral DNA might be getting “deployed into prod” and causing bad stuff to happen. The second ha-ha-contrarian-I-am-very-intelligent thought—also cheap to produce—was whether the ability to survive a viral onslaught brutal enough for the virus to embed itself in its quarry might be an indication that ancestral individuals had a more robust and aggressive immune system than peers who didn’t survive to reproduce. And if this could show up as a runaway inflammatory response in the current era. (From what I understand, psychiatric disorders are very very often accompanied by neuroinflammation. Practically… always?)
Such a great paper! I can speculate all this before I’ve even read the thing!!