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Cliff Edge: Illustration created by J. Chanam using an image (psychosis) from and icons from MS Office
New Paper: The Cliff Edge Model of the Evolution of Schizophrenia

Prose, poetry, creativity… but hang on, did Evolution extort a heavy price for such human ingenuity? Perhaps.

Of the many traits that distinguish modern humans from our close ancestors, Schizophrenia is one; a severe and disabling mental disorder unique to us Homo sapiens, which evolved as we diverged from  archaic hominids including the Neanderthals and the Denisovans. Schizophrenia’s high prevalence (1%) also make its an evolutionary paradox. How did it evolve and why, despite it severely reducing evolutionary fitness, has Evolution not weeded it out yet, or at least made it rare?

It is now well understood that schizophrenia — a highly polygenic trait — is an extreme manifestation of the cumulative effects of hundreds of genes including those that are responsible for the evolution of language, creativity and higher cognitive skills that make modern humans what we are.

In this new paper, Philipp Mitteroecker and Giuseppe P. Merola review the many theories proposed to explain the evolution of schizophrenia and test them against modern epidemiological and genetic evidence. They also present the first mathematical formulation of the Cliff Edge model of schizophrenia evolution, supporting the qualitative concept proposed by Ness (2004), significantly demystifying this evolutionary puzzle.

What is a Cliff Edge model: Imagine walking along a cliff – say, a pretty one carpeted with wild flowers. At some point, one reaches the cliff edge beyond which any more step would be a serious health hazard. In the case of schizophrenia, the cliff is made of a set of several hundreds of genes, which within a normal range of variation, confer cognitive, linguistic, and/or social advantages that are beneficial and therefore increase evolutionary fitness. But beyond a certain threshold which is referred to as the cliff edge, the cummulative effect of these traits is no longer beneficial; instead, these traits precipitate the onset of schizophrenia and reduce evolutionary fitness. With their mathematical model of the same, Philipp and Guiseppe show that it requires only very weak positive selection of the underlying trait(s) to explain today’s schizophrenia prevalence. According to the paper, “this prediction, along with expectations about the effect size of schizophrenia risk alleles, are surprisingly well matched by empirical evidence. The cliff edge model predicts a dynamic change of selection of risk alleles, which explains the contradictory findings of evolutionary genetic studies.”

And while modern psychiatric medicines have not yet found an effective cure or treatment, it is humbling to appreciate what it took for us to become human.


Publication: Mitteroecker, P., & Merola, G. P. (2024). The cliff edge model of the evolution of schizophrenia: mathematical, epidemiological, and genetic evidence. Neuroscience & Biobehavioral Reviews, 105636.