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Is Mental Illness Good For You?

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

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