Viral DNA in the human genome linked to major psychiatric disorders
medicalxpress.com
medicalxpress.com
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!!
> 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 for making the connection.
(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.
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.
Besides, a lot of people interested in a wild theory greatly ups the chances someone gets funding to test the hypothesis, no?
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.
Anything sarcastic or playful can be perceived as insincere.
I’d be happy to read more of your thoughts—you should keep writing.
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.)
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!)
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?
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.
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.
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956020/
https://www.statnews.com/2019/11/18/a-new-treatment-promises...
It seems almost certain that we will continue to find more DNA sequences that are correlated with increased intelligence.
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.
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.
So GATTACA (1997), a recommended movie treating the genetic discrimination, genoism, as main plot.
I don't think we will live to see it technologically speaking, but eventually our descendants may live through such hell of statistical speculation.
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.
Thinking mania can be controlled like an on-off switch.
Why even bother posting?
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.
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
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.
Being alive is the reward.
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…
Genes in Conflict: The Biology of Selfish Genetic Elements
by Austin Burt and Robert Trivers
https://www.amazon.com/gp/product/0674027221/
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.
Promoter genes are also part of evolutionary theory. You seem to think evolutionary theory came to an end in 1882. But a lot has happened since then.
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:
https://medicine.yale.edu/news/yale-medicine-magazine/articl...
https://www.quantamagazine.org/the-complex-truth-about-junk-...
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?
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.
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.
[0] mice float, they don't drown when they give up, assuming you take them out quickly enough [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401172/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353513/
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.
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?
Don't get me wrong, I'm not saying throw caution to the wind, but ludditism also isn't the answer.
What did it bring ? At what cost ?
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.
Did you have a point?
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.
For anyone that’s read it, I’m curious did they compare relative percentages of these DNA between haplogroups
Eg. Percentage of antisocial DNA in Europe vs Asia vs Bantu etc…
I fully agree with your perspective. Being a human is hard.
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.
Trauma, especially childhood trauma related to primary attachment figures can absolutely cause depression.
CBT has the same impact on the brain as antidepressants after only 3 months (assuming the cient is committed to CBT, most don't follow through).
Not being loved by a primary attachment figure doesn't just make people sad. It causes a great deal of emotional distress.
Most of the SSRIs were less than worthless for me, though finding the one that worked was life changing.
> CBT has the same impact on the brain as antidepressants after only 3 months (assuming the cient is committed to CBT, most don't follow through).
That's just another way of saying that CBT doesn't work for everyone. People following through for three months is a very self-selecting subgroup.
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.
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.
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!