> The whole point of evolution is that only genes that promote survival and replication can make it through
While this has been true in our past, we as a species have completely diverged from this. We do everything in our power to save every life no matter what the disorder or weakness. So it is no longer survival of the fittest in the traditional sense.
Whereas in the past someone with schizophrenia or major depression would not likely live a “normal” life and have children, now obviously it is very likely.
Genetic evidence suggest that the human population was bottlenecked to 3,000–10,000 individuals about 70,000 years ago. Not all that much time has passed since then, evolutionarily speaking, and whatever genetic predispositions were present in that tiny population are probably mostly still kicking around the gene pool. A disorder that doesn't cause problems before sexual maturity or that wouldn't pose an issue for a hunter-gatherer in the environment of evolutionary adaptation isn't really maladaptive, and there's no reason to suspect some number of such traits wouldn't be widespread.
It can also mean that the normal state of the brain exists near a small number of other stable modes, and that a wide variety of small nudges would have similar effects. The article mentions that a study of schizophrenia found that it was characterized in part by extremely rare mutations, suggesting that the brain is at an unstable local maximum, vulnerable to degrading into schizophrenia if unbalanced in any direction. Schizophrenia may in a sense be a much hardier fallback mode of brain operation.
Many of these "disorders" manifest before reproductive age; depression, anxiety, ADHD, bipolar, even schizophrenia occasionally.
Think about the condition we currently call the "disorder" ADHD.
We can easily imagine how the behavioural tendencies ascribed to it would have been beneficial in hunter-gatherer times; i.e., it would be beneficial to the tribe for a certain number of people to be restless and explorative, rather than being conformist and content doing repetitive tasks. Same goes for bipolar; think about how many of our leading writers, inventors, musicians are diagnosed bipolar, and how useful it would always have been to have had a few people with that kind of creativity and propensity for bursts of novel productivity in the tribe.
And I can easily think of ways depression and anxiety are adaptive and supportive of survival, rather than not (for depression it's the ability to contemplate/reform a troubled life, and anxiety it's the avoidance of danger). Even schizophrenia in certain circumstances.
And of course when we invoke Occam's razor, it makes far more sense that these genes are there because they're beneficial, rather than being there due to a historical accident.
For example, schizophrenia. It doesn't generally show itself until one's early 20's: there are many college students who find their studies halted because of it. It is really easy to have children before this. Depression can render itself after having children, especially in women. We treat it now.
Lots of non-psychiatric disorders are similar: no problems until early-to-mid adulthood. Plenty of time to have children beforehand.
The difference now isn't that genes aren't passed along to children, but more that we try to give folks a more normal life and less misery. And we frown upon the abusive practices that were so commonplace in asylums of yesteryear.
There seems to be a bit of replying to the wrong comment going on, but I'll comment here in response to you and the parent...
This line of argument is flawed because:
1) Plenty of depression, anxiety and of course ADHD occurs in childhood, while bipolar and schizophrenia more commonly occurs in late adolescence or early adulthood. Plenty of reproduction happens - particularly by men of course - at ages later than these when these illnesses can manifest (we can even see how some men with ADHD or bipolar tendencies have reproduced at higher rates than other men, and rationalise why this would have been the case through evolutionary history).
2) The suggestion that such widespread tendencies are in the gene pool only as an undesirable accident doesn't pass Occam's razer. We must assume they are there because they have been selected for, unless there is evidence to the contrary, which nobody in this whole thread has been able to offer.
3) We can easily see reasons why it has been beneficial to have some level of propensity for tendencies like depression, anxiety, ADHD, bipolar and even some schizophrenia in the gene pool.
I don't think this is right. I understand the basis for thinking it; I've spent much of my adult life accepting or assuming this is how it works. But the more I learn (and I spent a whole lot more time reading scientific papers on the topic this afternoon), the less it holds.
First, the logic assumes the genetic coding for these conditions is never helpful to survival/replication, which as I've pointed out in several other comments, is demonstrably false.
But even if that coding really was never ever helpful, the theory relies on the notion that unhelpful DNA just keeps hanging around on the genome anyway.
Though I can't find a big amount of research on this (particularly regarding humans), there is evidence of "genome streamlining" where genes that serve no purpose get stripped out of the genome. This is necessary because it there is a cost in retaining DNA (continuing to transcribe it and modulate it), so it's far more efficient and thus helpful for survival to remove it.
The main research I've found on this pertains to birds and bats [1] (in which it is particularly important due to the metabolic cost of flying), but it would be reasonable to expect it also happens in primates, including humans, at least to some degree.
I concede this is speculative, but it's compelling.
Even still, the validity of my main point doesn't rely on this being true. We know that most mental "illness" tendencies are sometimes useful for survival/replication. That's what matters most here.
If you want a few well-known examples: Cystic fibrosis, Muscular Dystrophy, Canavan Disease, and Hemophilia.
There's lots of obvious bad stuff floating around in our genomes. It's not surprising that the roots of mental illness, heart disease, diabetes, and others are hereditary too.
Of the conditions you mentioned, cystic fibrosis and haemophilia are due to specific, single-gene mutations, and both are quite rare.
There's a huge difference between conditions that are caused by a single-gene defect vs conditions that sometimes arise when a combination of genes are present/expressed in combination with other (e.g. environmental) factors.
> There's lots of obvious bad stuff floating around in our genomes
Not handwavy. They were specific. The article makes this exact point:
“In the genes
------------
One pillar of this future approach is a better understanding of the genetics of mental illness. In the past decade, studies of psychopathological genetics have become large enough to draw robust conclusions.
The studies reveal that no individual gene contributes much to the risk of a psychopathology; instead, hundreds of genes each have a small effect. A 2009 study found that thousands of gene variants were risk factors for schizophrenia. Many were also associated with bipolar disorder, suggesting that some genes contribute to both disorders.
This is not to say that the same genes are involved in all brain disorders: far from it. A team led by geneticist Benjamin Neale at Massachusetts General Hospital in Boston and psychiatrist Aiden Corvin at Trinity College Dublin found in 2018 that neurological disorders such as epilepsy and multiple sclerosis are genetically distinct from psychiatric disorders such as schizophrenia and depression (see ‘Mental map’).”
My point is that it's not "obvious bad stuff", and the continued presumption that it is is probably the reason why so little progress has been made in the field.
Even that passage of the article you quote doesn't characterise the genes as "bad stuff"; just known genes that seem to correlate with the (contextually undesirable) conditions manifesting.
You asked someone for examples. They gave them to you. You decried those examples as handwavy and not specific (which they clearly were not). I countered that they had been specific and not handwavy, explained why, and pointed out that moreover this ground had already been covered in the article and that the article concurred with those examples.
Your reply to me misses the point that I was making and argues against a point I wasn't making – which strikingly is the very thing that prompted me to counter your top-level post.
Firstly, please let's drop the hostility. I'm not here to win arguments or score points. I engage in these discussions to test my understanding of the topic and further develop my knowledge, and to share my perspective with others who are open to it.
In response to your comment:
> You decried those examples as handwavy
To clarify, I didn't say the examples were handwavy; I pointed out the crucial distinction between disorders specifically attributable to specific gene defects (like Huntington's and cystic fibrosis), vs. conditions that arise through the interaction between positively-selected genes and environmental triggers. It's a category error.
What I referred to as "handwavy" was the sentence "There's lots of obvious bad stuff floating around in our genomes" - specifically the phrase "lots of obvious bad stuff".
I was calling this out as an unexamined assumption, rather than a the simple incontrovertible fact that it was presented as.
> and pointed out that moreover this ground had already been covered in the article and that the article concurred with those examples
But the article doesn't concur with those examples.
The commenter listed illnesses caused by specific-gene defects, and the passage you quoted names several psychiatric conditions that are known to not be caused directly by specific-gene defects. Again, a category error.
> Your reply to me misses the point that I was making and argues against a point I wasn't making – which strikingly is the very thing that prompted me to counter your top-level post.
You seem to have read my top comment as directly critiquing the article itself, rather than the approach that has dominated the field (along with the rest of medicine) for decades. (Fair enough that you read it that way.)
I acknowledged to you that the article conveys that some researchers are rethinking the approach, but I don't see evidence of enough of a rethink.
Most importantly, they're still looking at things mechanistically; studying brain structure, going deeper trying to find particular genetic "causes" (after the many years of looking at genes have yielded little useful insight), and proposing some mysterious "p factor" and asserting: "if it is real, it has a startling implication: there could be a single therapeutic target for psychiatric disorders". That's what I mean by the "mechanistic lens".
The core position I'm arguing against, which is presented in the article and by several commenters, is that mental "illness" is likely caused by "bad" genes or biological processes "going wrong". My position is that we should generally assume that the genes are meant to be there, and focus on what in the person's life is causing the genes or biological systems to express in an undesirable way (which is what the practitioners I've named have been doing for years/decades with great success).
I've expressed my position at length in other comments. At the time of writing, the position I've articulated in detail hasn't been refuted. I'd welcome anyone to do so, so I can learn more about the topic.
Just as is the case for mental "disorders", none of these conditions are attributable to a known gene or gene combination, or have a 1:1 match between carrying a certain gene combination and having the disease (meaning there must be an environmental trigger in addition to the genetic predisposition).
For almost all of them (possibly all of them in some cases), there is evidence of links with auto-immunity and the presence of active pathogens (including viruses, bacteria, funguses, etc), suggesting that the illness is related to the body's efforts to fight off or cope with pathogens, or to some effect of the pathogen's activity.
Those who invoke conditions like Huntington's Disease and haemophilia are on more solid ground, as these are directly attributable to single-gene mutations. But these conditions are also very very rare, unlike mental "disorders".
You asked for 'inheritable genetic physical diseases'. I gave you a list. Now it seems you actually want a list of 'mendelian' genetic disease, i.e. those which are caused by a single genetic variant.
Mendelian diseases are not the only sort of genetic disorder. This is a misunderstanding of genetics.
Source: I was a university researcher in psychiatric genetics
I'm making the distinction between illnesses that are directly caused by an identifiable genetic defect (e.g., Huntington's), and conditions that can arise when a certain combination of genes/genetic expressions are present but even then only arise some of the time.
As a professional in the field you'll know the terminology better than me and that's great, but you must understand the distinction I'm trying to make.
In the former case, we can clearly see a 1:1 causal link from genetic defect to the manifestation of the disease (whether it's a single gene or more is not central to the point).
In the latter case, the genetic predisposition is there, but there must also be some other form of conditional trigger.
One of your examples with which I'm quite familiar is asthma, which I've experienced at times in my life (though neither of my parents did).
I started experiencing it at about age 9 (as an allergic reaction to dust, dust mite and possibly other chronic infections I had at that age). Then it stopped in my mid teens. Then it started again when I smoked tobacco in my 20s, then stopped as soon as I stopped smoking. Then it started again in my mid 30s when I was experiencing severe stress and anxiety, then it stopped when I undertook a combination of approaches to reduce the stress/anxiety in my life, and a dietary program and other remedies to reduce chronic infections. That was 6 years ago and I've not needed asthma medication ever since.
The point is, there's nothing genetically deterministic about my asthma, given that it's come and gone through out my life and has been clearly influenced by environmental factors.
Further, it's plausible that the asthma has been a beneficial symptom, to protect my body from allergens and pathogens, and signal that I needed to change my lifestyle. Certainly, it was a big part of what signalled to me that I need to stop smoking, and later to clean up my diet and make other improvements to my emotional and physical health.
As I've proposed in several other comments, it's just as plausible that the conditions we regard as mental "illnesses" are likely not genetic flaws or other malfunctions at all, but rather beneficial adaptations that have been selected for by evolution (e.g., it's obvious how the presence of "ADHD" in a small percentage of the population would have been beneficial in prehistoric human tribes).
Given this, our real challenge is to do a better job of interpreting and responding to these conditions, as several practitioners going back decades have already figured out how to do.
If that works for you I don't want you get you of that view, but that seems to romanticize illnesses too much for my taste.
Almost every disease can be traced back to genes (as you said it doesn't matter how many of them). Of course how much those genes play a factor varies immensely based on many factors. And there absolutely is something genetically deterministic about your asthma - you just have found another way of shutting down the biochemical pathways that would normally lead you to have symptoms.
To anyone in research in the field, the distinction you are trying to make is moot. Huntington's is just as regulated as any of the "conditional diseases" you try to put in a separate category. Sure, it has a more deterministic ultimate fate, but it's gene expression likely varies by a lot of factors too, especially between different cell types. And with that exact differential view is how all diseases are studied.
You haven't said anything about being a qualified expert in the field, so I'll assume you're not - please correct me if otherwise.
> To anyone in research in the field, the distinction you are trying to make is moot
I wouldn't think this is true; it's about the most important distinction there could be in genetics - i.e., flaws/defects of specific genes vs traits/predispositions that have been selected for over the history of evolution.
If a trait has been selected for over tens/hundreds of thousands of years of evolution, it's a mistake to try and "cure" it; it's not something that can be cured, as it's there for an important reason. The right approach is to understand the conditions that trigger the symptoms, and create better conditions so the problem corrects, just as I've done.
> If that works for you I don't want you get you of that view, but that seems to romanticize illnesses too much for my taste.
This is an emotion-driven (and rather patronising) response, whereas I'm focused wholly on what is scientifically plausible and demonstrable.
I welcome new evidence to challenge the position I've put, but so far it hasn't been forthcoming.
> You haven't said anything about being a qualified expert in the field, so I'll assume you're not - please correct me if otherwise.
Not sure if that's enough qualification for you, but I'm a biochemistry undergrad with the goal of contributing to drug development in the future. The viewpoints I express here come from regularly reading recent papers related to mechanisms of various diseases, as well as what I've learned by talking to our professors and how we talk about diseases in class. (I also have an irrelevant background in software engineering, so I'm probably not as young and unexposed to the world as you might assume).
> If a trait has been selected for over tens/hundreds of thousands of years of evolution
That's simply not true that all (or even most of) our genes have been selected for "for tens/hundreds of thousands of years". Most diseases that occur after reaching reproductive age are not strongly selected for (this also holds true for animals). On top of that human social structures also help to weaken/circumvent evolutionary pressure.
> it's a mistake to try and "cure" it; it's not something that can be cured, as it's there for an important reason
> create better conditions so the problem corrects, just as I've done.
Not everything is there for an important reason. I'm lactose intolerant (also only attained after turning 18, so evading evolution). There is a long outdated evolutionary reason for turning of milk consumption in adults. There is not a good reason that applies in this day and age to turn of additional ways of energy supply to the body.
Yes, we do also look at the evolutionary circumstances of a gene in drug development, but that's mostly to reduce side effects by finding out what pathways could be connected.
I also don't see a big distinction between "curing" it "creating better conditions". Isn't curing it a way to create better conditions? Coming back to lactose intolerance, I can obviously always try to avoid lactose - or I can sometimes take lactase pills when it's easier in social situations.
> I'm focused wholly on what is scientifically plausible and demonstrable.
I'd like to see scientific evidence that bodies develop diseases to get people "to clean up their diet" or be introspective. Everything I see in terms of how individual biochemical pathways can be turned on/off without far reaching repercussions points into the opposite direction of us being so complex and interconnected that nothing should be tinkered with.
As I said I'm happy for you (honestly!), that this is how it worked out for you, but there are also a number of different events/experiences that could've lead you on the better path you are on now. No need for diseases to trigger that.
Also as a response to something you said in one of your other comments:
> Like so much in medical research, efforts are governed by what research will be funded, and ideally what will lead to the discovery of a drug or intervention that can generate billions of dollars of revenues. Those researchers who figured this stuff out decades ago don't need to be considered.
While this is of course true, that's not the only reason why the vast majority of people prefer taking medication for their diseases. People are lazy and changing habits is hard. For the same reason, it's most efficient (not effective!) to prescribe drugs to their patients, because they can't start lifestyle coaching every patient to change their diet.
Just look at cardiovascular diseases! It's been a leading cause of death for a long time, even though we know that improving levels of exercise and adjusting your diet can improve the odds a lot. This doesn't mean we shouldn't put money towards e.g. funding a drug that removes plaque from arteries.
I'll try to reply quickly, as I think we at least mostly understand each other, and it's time to sleep where I am.
> That's simply not true that all (or even most of) our genes have been selected for "for tens/hundreds of thousands of years". Most diseases that occur after reaching reproductive age are not strongly selected for (this also holds true for animals). On top of that human social structures also help to weaken/circumvent evolutionary pressure.
All the conditions we're talking about can very often express before reproduction happens; anxiety, depression, ADHD, bipolar, personality disorders, even schizophrenia (though that's later than most but still by the early 20s). And it's always been common for men to reproduce well into advanced age.
I gather you're arguing that mental "illness" hasn't actually been positively selected for by evolution, but in fact is just caused by crappy DNA that entered the gene pool by mistake and has stayed on for the ride.
It's a coherent claim, but doesn't really pass Occam's Razor.
For all the conditions I listed above, we can see how, in certain circumstances, they can be beneficial either to the individual or the group, so we don't need to conjure up an assumption that their emergence and persistence were undesirable accidents.
> I'm lactose intolerant
I'd be happy to research and debate this further at a later time if it turns out the topic materially hinges on this
> I also don't see a big distinction between "curing" it "creating better conditions". Isn't curing it a way to create better conditions?
It's a case of treating the symptoms vs the cause that pertain's to one's own life (their life experience and/or their environment).
Take the ADHD example. Current common treatment is to prescribe amphetamines. Future treatments according to this article might be to "switch off" the gene that causes ADHD-type behaviour. My "better conditions" approach is to look at the kid's overall personality and environment, investigate whether there's any trauma or distress underlying the behaviour (which is tragically often overlooked in the current treatment model), then once you've ensured the kid is in a safe and nurturing environment, if they're still hyperactive or unfocused, look at their whole personality and direct them towards activities that are suited to their talents and strengths (this happens sometimes but not nearly enough).
Using drugs or genetic treatments or anything else to "switch off" the ADHD is most likely to end up being somewhere between a lamentable underutilisation of talent/ability, and an egregious act of neglect/abuse.
When we treat genes as the "cause", we overlook so much in someone's life experience and environment that is highly controllable and that can have a far greater impact than by interfering with genes or biochemical pathways.
> I'd like to see scientific evidence that bodies develop diseases to get people "to clean up their diet" or be introspective.
The very existence of physical discomfort/pain or emotional distress is a demonstration of the biological signals we've developed to motivate changes to our conditions or behaviour.
We all know that eating too much of the wrong kind of food or drinking too much alcohol leads to physical and emotional pain/discomfort/distress that tells us to change.
Same goes for dysfunctional behaviour that leads to a relationship breakup or social rejection, leading to a period of introspection.
Sometimes the link between pain/illness and behaviour/environment is not so clear-cut, so we need to see a practitioner or do some research of our own.
But there's nothing in the least bit fringe or controversial about this concept.
> People are lazy and changing habits is hard
> we know that improving levels of exercise and adjusting your diet
I keep hearing this from experts on medicine and physiology. Some of them still dispute the "sugar is more harmful than fat" evidence (which I know is a separate issue that I don't want to start debating here/now).
I'm more optimistic about human potential.
People respond to incentives, and people will happily follow practices that clearly deliver benefits.
I know this from personal experience. I drank heavily, ate terribly, smoked and didn't stick to exercise. I tried doing everything mainstream health advocates recommended, but didn't get sustained results so I lost motivation and went back to bad old ways.
Then I found approaches that worked, and I've happily done them every day for over 8 years, because I've found that when I do, my life just keeps getting better.
> But these conditions are also very very rare, unlike mental "disorders".
Hopefully you accept statistics even if I cannot point to individual genes.
For for example ADHD I cannot give you a specific set of genes, but it is widely known and accepted to be very strongly related to if your ancestors had similar traits.
Do you have an explanation for this except the genes?
> Do you have an explanation for this except the genes?
Yes of course - the environmental/experiential conditions in which the carrier of the genes find themselves.
Remember, ADHD is just a culturally defined description of behavioural tendencies, not a genetically hard-coded outcome like the shape of someone's face, so it's a mistake to think of them as being genetically determined in the same way.
Of course the genes someone inherits from their ancestors will influence their behaviour, but genes express differently depending on many conditions, and for behaviour it's highly contingent on one's own life experiences; indeed it's extremely important for survival and continued evolution that one can adapt their behaviour to the environment in which they live.
Even recent twin studies [1] don't find anything more than about 75-80% heritability of "ADHD" diagnoses, so you still need to explain the other 20-25%.
Yep but the whole point is that it's not 100% the way it is with the right genetic conditions for disorders like Huntington's Disease or Down Syndrome.
Looking at the ADHD example, aside from the genes, consider what else is consistent: same gestational environment (mother's food, air, water, emotions, microbiome), possibly the same living environment in early life (I'm not clear on how many of these twins were separated, and if so, at what age), but even if they were separated, they're still living in the same time in history, likely the same city/country, likely at a similar socioeconomic level, they have the same appearance/height (so people respond to them similarly) and if they were separated, both experiencing trauma of separation (both from a sibling, and one or both from parents).
So there's a whole lot going on that can explain the high heritability figure.
But even if you disregard all of that, you still have to explain the other (at least) 20-25%.
Huntington's disease is one of a small number of conditions that is caused by a single-gene defect (along with haemophilia, and a few others).
It's very rare.
What is known about mental "illnesses" are that they sometimes manifest when certain combinations of genes are present, but not always, and when you look at the details of cases you can pretty much always find an outer-world factor that triggers the state (e..g, abuse, trauma, neglect etc).
There are plenty of inheritable genetic physical diseases. The evolution is not machine to make us perfect not God. You can't treat it this way.