Is Mental Illness Good For You?

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Mirrored from http://wiringthebrain.blogspot.com/

Mental illness is surprisingly common. About 10% of the population is affected by it at any one time and up to 25% suffer some kind of mental illness over their lifetime. This has led some people (many people in fact) to surmise that it must exist for a reason – in particular that it must be associated with some kind of evolutionary advantage. Indeed, this is a popular and persistent idea both in scientific circles and in the general public. (See the recent article “Depression’s Upside” from the New York Times Magazine, for example: http://www.nytimes.com/2010/02/28/magazine/28depression-t.html).

Such theories come in two main varieties – the first, that mental illness confers some specific advantage to those afflicted; and second, that the mutations which cause mental illness in one person’s genetic background may confer an advantage when they are in a different genetic background (balancing selection). Both of these suffer from some misconceptions about how evolution by natural selection works. The intuitive appeal of the “survival of the fittest” metaphor may have something to do with this – the actual mechanisms of natural selection are more nuanced.

Natural selection works by changing the frequencies of genetic variants in the population. If a particular gene, gene X, comes in two varieties, X and X’, and one of these (say X’) tends to increase the evolutionary fitness of the people who carry it, this means they will have more offspring than people who do not carry that variant and the frequency of the X’ variant will increase in the next generation (at the expense of the X variant). Variants that increase fitness a lot rapidly out-compete the alternative version and soon all copies of the gene will be of that type (it becomes “fixed” in the population). In contrast, new variants that arise which seriously decrease fitness will tend to be rapidly weeded out of the population.

We know that psychiatric disorders can be caused by such genetic variants (mutations). What are the likely effects of such mutations on fitness? Is there any reason to think they may confer some kind of advantage on carriers? Some examples of the types of advantages that have been postulated include that schizophrenics may have been seen as shamans in ancient societies, that people with bipolar disorder may be more creative (it is especially common among poets, for example), or that depressed people are actually more realistic and better able to concentrate on a problem. The trouble with these theories is that natural selection doesn’t care whether you are good at poetry or solving problems through prolonged rumination. Natural selection only cares how many children you have – more accurately, how many children you have who survive to breed themselves.

If it were true that people with mental illness live longer and have more surviving offspring than people without, then this kind of theory might be viable. In fact, the evidence is overwhelmingly the opposite. First, mortality rates before or during the reproductive period for depression and schizophrenia are two to three times higher than the general population. Second, surviving patients with schizophrenia have only 1/3 the average number of children – this general trend seems to also hold for other psychiatric disorders. Variants that increase risk of mental illness thus demonstrably and significantly decrease fitness and should be rapidly selected against; i.e., they would never rise to a high frequency. (This is one of the major arguments against the so-called common disease/common variants hypothesis – for more on this see: http://wiringthebrain.blogspot.com/2009/07/hot-news-in-genetics-of-schizophrenia.html).

But wait – maybe these disorders are deleterious in our current environment but conferred an advantage of some kind in primitive environments. (Much as variants that predispose to obesity or diabetes in our current environment might have been adaptive in an environment where high-fat food was very scarce). This is certainly conceivable, although there is no evidence or even good reason to think that this was the case. In fact, through some simple modeling it can be shown that the current rates of mental disorders do not fit such a scenario (see Keller and Miller).

An alternative suggestion is that the variants that predispose to mental illness do so only in some genetic contexts – only in the presence of additional variants. In other genetic backgrounds, perhaps they confer an increase in fitness which counterbalances the decreased fitness in mental illness sufferers. This scenario of balancing selection is modeled on very rare cases like sickle-cell anemia, where a particular mutation causes a deleterious condition when present in two copies, but confers an advantage (increased resistance to malaria, in this case) when present in only one copy. While this kind of model is difficult to disprove, there are strong arguments against it and no evidence that it applies – relatives of schizophrenics do not show increased fertility rates, for example.

So why is mental illness so common? If it’s so bad and is caused by genetic variants, why hasn’t natural selection gotten rid of them all by now? Well, the answer is it does – in fact, it’s very good at getting rid of them. Unfortunately, new mutations keep arising all the time. Rates of mental illness are higher than those of other genetic disorders because it takes the combined actions of thousands of different gene products to wire the staggeringly complex human brain. If any one of a large number of these genes gets mutated, then development of the brain may be compromised and this may ultimately result in a psychiatric disorder. There is thus no paradox to explain – common disorders like schizophrenia are really umbrella terms for lots of distinct genetic disorders, each of which is extremely rare, due to the efficient action of natural selection. All of these theories are thus offering solutions to a problem that doesn’t exist.

For more on this topic see the extremely insightful article by Keller and Miller.

Keller, M., & Miller, G. (2006). Resolving the paradox of common, harmful, heritable mental disorders: Which evolutionary genetic models work best? Behavioral and Brain Sciences, 29 (04) DOI: 10.1017/S0140525X06009095

17 Comments

  1. right, so you’re saying it’s just the constant mutational load which has to be balanced against selection. but one issue is that you’re talking about stuff like schizophrenia, where the frequency in the population is nowhere like 10-25%. “mental illness” is a big term, and encompasses stuff that i think is a product of cultural expectation and norms at one end (more numerous) and congenital neurochemical dysfunction (at the other).

  2. There is in fact another option which has not been discussed here: a genetic variant may increase reproductive success when the carrier does -not- develop a disorder, and at the same time increase the risk of developing the disorder.

    Sexual selection theories of schizotypy work like this, and indeed people with high schizotypy but no diagnosed schizophrenia/bipolar disorder turn out to have more sexual partners (see Nettle & Clegg, 2006). Just looking at the average fitness of the tiny minority of those who develop the disorder (the unlucky ones) can give a very misleading picture. This is true of all high-risk strategies – you trade an average cost against highly variable chances of success. Such strategies can be especially adaptive when reproductive success is highly skewed (e.g., polygynous societies). One needs to calculate the fitness of everyone carrying the variant, not just of those who happen to fall on the losing side.

  3. You’re right, the figures of 10% at any one time and 25% over a lifetime are for people suffering from any of a large list of “mental illnesses”, including schizophrenia, autism, depression, but also drug addiction of substance abuse disorders. The definition of some of these is certainly culturally dependent.

    The arguments presented above are most applicable to those disorders which are individually common but also lead to a large reduction in fitness, such as schizophrenia, bipolar disorder and unipolar depression.

  4. Nice article. I’m kind of surprised you didn’t talk at all about possible interaction effects with the environment, which may account for a fair bit of the heritability. These rare mutations may only lead to schizophrenia when combined with certain deleterious environments. I believe this is one possible explanation for the higher rates of schizophrenia in urban as oppposed to rural areas. A gene-environment interaction may also be involved in the increase in autism (beyond more inclusive diagnosing). IMO, I think the solution is a bit of all three: rare mutations, many common variants of small effect, and the interaction of these genetic variants with the environment.

  5. Interesting, and ultimately testable. If when we look at the variants that cause these diseases they do indeed look like random noise, then this argument is probably correct. But if some of them stand out as being of unusual antiquity (or otherwise show signs of being maintained via balancing selection), then it’s wrong.
    Personally I think he’s too quick to dismiss the possibility of heterozygote advantage. He mentions the classic example of sickle cell anemia and then dismissively declares such cases as extremely rare. But we have no idea whether such cases actually are rare or not – it may be that extreme examples like sickle cell are rare, but alleles with smaller fitness effects might be more common and harder to identify. Further, the fact that modern-day relatives of schizophrenics don’t have increased fertility doesn’t mean they might not have had some advantage in a prehistoric setting, which we would no longer be able to detect.
    As regards schizophrenia specifically I would be more inclined to suspect some pathogen or factor in the modern environment to which schizophrenics have a partly-genetic vulnerability. If it had been common in prehistory we would have more early reports of such behaviors. But in the case of manic depression balancing selection seems more plausible; too much of the behavioral repertoire of the bipolar individual seems situationally advantageous for me to dismiss the idea so casually.

  6. I know someone with a variant of Bipolar disorder, who suffers from Hypomania which helped him become a hugely successful litigator. Three of his four kids are also highly successful, while one suffers from Bi-Polar disorder.

  7. Also wasn’t there a paper mentioned here or elsewhere, which showed that High IQ people with some SNPs linked to Schizophrenia are more creative than average, where low IQ people with these same SNP’s suffer from the disease??

  8. Mental illness (legitimate ones, not the goffiness listed in the DSM) are probably just spandrals. Some consequence of higher brain function probably but not an ends in and of themselves.

  9. Why wouldn’t some mental illnesses be caused by infections?

    For example, if you get three or four colds per years, and they average 10 days each, then you are metabolically sick ten percent of the time, the same figure Razib cites for the prevalence of mental illness.

    People who currently have colds are less likely to conceive children and, in Malthusian societies, are more likely to die soon, such as by developing pneumonia or by lacking the endurance to catch game or get all of the harvest in.

    So, why haven’t colds been eliminated by natural selection? Because cold germs are co-evolving along with defenses against them.

    So, why couldn’t some mental illnesses be caused by infections? It’s commonly observed that psychiatrists are more prone to mental illness than the average — perhaps they get some mental illnesses from shaking hands with or being sneezed upon by their patients?

  10. That’s an interesting question Steve. There are indeed some infections which can lead to psychotic or other psychiatric symptoms, including syphilis and rabies, for example. However, there is no evidence that chronic psychiatric disorders are caused by some infectious agent, and there is very strong evidence indeed that they are caused by variants in genes (with some environmental contributions and probably a significant effect of stochastic developmental variation).

  11. How do we know this gene variation doesn’t affect the immune system and thus makes some people more or less resistant to infections that affect the mind?

    There are a lot of possible examples of infections affecting the mind:

    Tuberculosis, for example, was widely believed in the Romantic era to make poets and painters more brilliant and unstable.

    The theory of Natural Selection was dreamed by Alfred Russel Wallace during a fever.

    Bow do we know that other, still unknown infections don’t play a role in mental illnesses?

  12. Huxley floated that idea as long ago as ’64, he suggested having resistance to shock, autoimmune disease, or infection increased schizophrenics’ reproductive fitness.

    But there could be another advantage altogether – Albert Einstein and James Watson both had sons who were schizophrenic

  13. If I recall correctly, schizophrenia is more common in urban than rural areas, and more common in people born at certain times of the year.

    One hypothesis that (more or less) fits is that symptoms are due to prenatal infection by an agent that is more common in towns (where there are more people to catch it from) and more common in winter (cf. influenza).

    Pure mutation/selection balance doesn’t quite explain the pattern.

    As Steve says, if the underlying cause is infectious, genes may affect resistance to infection.

    P.S. “mental illness” groups together many different kinds of condition. Depression, schizophrenia, autism and drug addiciton may turn out to have different causes, or kinds of causes.

    P.P.S. I suspect that people with prexisting psychiatric conditions are more likely to want to become psychiatrists, rather than the mechanism being psychiatrists catching an infection from their patients. Dealing with psychiatric patients on a regular basis might be depressing, of course.

  14. Greg Cochran suggested that schizophrenia is caused by infection, based on the fact that those who have it are disproportionately born in cold months.

  15. Issac Newton has been suggested to have had schizotypal personality disorder which some say Einstein showed signs of, as it is found in the families of schizophrenics maybe it’s being a relative of a mentally ill person that is advantageous

  16. There is indeed a well-documented effect of several environmental factors (urban location, winter birth, maternal infection) which all suggest that maternal infection during gestation, particularly during the second trimester, can lead to an increased risk of schizophrenia. The common interpretation of that effect, which is well-supported and which I think is correct, is that the maternal immune response releases cytokines which affect the neural development of the fetus. This fits with the theory that schizophrenia is a disorder of neurodevelopment, which is supported by anatomical evidence of disruptions in cell migration and neural connectivity and also by genetic evidence, as almost all of the genes thus far implicated in the disorder are involved in neurodevelopment.

    In response to some of the other comments suggesting various advantages of alleles predisposing to schizophrenia or bipolar disorder, either in the sufferers or their relatives, I return to the main argument of the post: natural selection only cares how many offspring you have who survive to reproduce themselves. Arguments about creativity or genius are not relevant if these traits do not increase fecundity. More fundamentally, what is being proposed is that such mechanisms are simply unnecessary – the disorders are common and remain common because it takes a lot of genes to wire the human brain. Mutations in any of hundreds of such genes may alter neurodevelopment in a way that ultimately manifests as schizophrenia (or bipolar disorder or autism or depression, etc.)

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