Thursday, May 15, 2008

Balancing selection--no answer for schizophrenia

Many have asked why genes that cause such a serious disease persist, and a number of evolutionary hypotheses have been inspired by the kind of balancing selection that explains the persistence of genes that cause sickle cell disease. A new article by Adriaens debunks such hypotheses. He offers a nice review of studies about the reproductive success of people with schizophrenia, although I think he discounts excessively the evolutionary significance of a 50% fitness decrease for male schizophrenics.

It seems to me that he is absolutely right, however,
to point out data that undermine hypotheses based on covert benefits of schizophrenia genes. He generalizes about evolutionary psychiatrists as if they are not only all in one category, but as if they all think the same things. This is especially surprizing given his emphasis on the mistake of assuming that schizophrenia is a natural category. It is so important to criticize hypotheses, not people or groups.

There is much additional useful in his paper, especially his outline of evolutionary reasons why the genetic factors in schizophrenia will be much more complex than we have imagined. This all fits very nicely with other reports this week about the genetics of schizophrenia I do think, however, that we do need to ask why such a highly heritable devastating disorder persists. Balancing selection is not likely. It could be just that new mutations happen. But I think that the high heritability has kept attention focused on the level of the gene, when the problem may well be in constraints and trade-offs at a higher level. See a previous post for more on this.

1 comment:

Anonymous said...

"He offers a nice review of studies about the reproductive success of people with schizophrenia, although I think he discounts excessively the evolutionary significance of a 50% fitness decrease for male schizophrenics."

Contemporary reproductive success will likely differ from historical values.
The latter rather than the former is significant for explaining current population composition.
Also note that only a small increase in reproductive success in relatives would be sufficient to outweigh lower fertility of patients. (I've read somewhere that +5% would be sufficient.)

The balanced selection argument can also nicely explain why schizophrenia has been sustained
while the very genes which influence the risks of schizophrenia have undergone strong recent selection pressure. [1]

Furthermore, it is now well established that schizotypy and bipolar disorder, both genetically related to schizophrenia, are positively correlated with creativity.
Note that creative advantages of bipolar genes are rarely casted into doubt --
while having a psychotic relative with one of the two illnesses greatly increases
the likelihood of having the other.

On the cognitive side, schizophrenia leads to low density of dopamine D2 receptors in the thalamus and reduced lateralization. To a lesser extant, these can also be seen in:
a) relatives of schizophrenic patients
b) creative people [2].

Hence, there is both brain-level and behavioral-level evidence for relating schizophrenia to increased creativity in relatives, explaining its evolutionary persistence.

[1] Genetic Markers of Human Evolution Are Enriched in Schizophrenia.
[2] Thinking Outside a Less Intact Box: Thalamic Dopamine D2 Receptor Densities Are Negatively Related to Psychometric Creativity in Healthy Individuals