Schizophrenia Is the Price We Pay for Minds Poised Near the Edge of a Cliff

Summary

This post discusses cliff-edged fitness functions by Randolph Nesse (psychiatrist and one of the founders of evolutionary medicine) and the 2024 paper, “The cliff edge model of the evolution of schizophrenia: Mathematical, epidemiological, and genetic evidence,” by Philipp Mitteroecker and Giuseppe Pierpaolo Merola.If you are a regular reader of this newsletter, and it deepens your intellectual life, consider a paid subscription to support this effort.The persistence of schizophrenia is an evolutionary enigma. It is a disabling psychiatric condition that reduces the likelihood of having children, and yet it has roughly 1% lifetime prevalence worldwide. Traditional evolutionary hypotheses, such as those invoking kin selection, mutation-selection balance, and evolutionary mismatch don’t quite explain this.For instance, if schizophrenia risk genes were not under positive selection, we would expect them to be purged from the gene pool over thousands of years. The process will be slow, but it will happen (this is not the same as saying schizophrenia itself can be eliminated, since it is highly polygenic and the pool of risk genes is not static). Let’s say schizophrenia is associated with a 50% loss of reproductive fitness in 1% of the population (and there is no offsetting benefit in the rest of the population), then it would take roughly 180 generations to cut the rate in half and about 560 generations to reduce it to one-tenth of its original value (Mitteroecker & Merola, 2024). We’ve had a comparable number of generations since the Neolithic era, but as far as we know, the prevalence of schizophrenia has not decreased in the manner anticipated. At the same time, we do not have evidence for ongoing positive selection for schizophrenia risk alleles; in fact, schizophrenia alleles appear to be under negative selection at present, although evidence suggests many have been positively selected in the evolutionary past.One proposed solution is to think of schizophrenia in te...