The cliff edge model of the evolution of schizophrenia: Mathematical, epidemiological, and genetic evidence

Philipp Mitteroecker, Giuseppe Pierpaolo Merola

Publications: Contribution to journalArticlePeer Reviewed

Abstract

How has schizophrenia, a condition that significantly reduces an individual's evolutionary fitness, remained common across generations and cultures? Numerous theories about the evolution of schizophrenia have been proposed, most of which are not consistent with modern epidemiological and genetic evidence. Here, we briefly review this evidence and explore the cliff edge model of schizophrenia. It suggests that schizophrenia is the extreme manifestation of a polygenic trait or a combination of traits that, within a normal range of variation, confer cognitive, linguistic, and/or social advantages. Only beyond a certain threshold, these traits precipitate the onset of schizophrenia and reduce fitness. We provide the first mathematical model of this qualitative concept and show that it requires only very weak positive selection of the underlying trait(s) to explain today's schizophrenia prevalence. 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.

Original languageEnglish
Article number105636
Pages (from-to)105636
JournalNeuroscience and Biobehavioral Reviews
Volume160
Early online date2024
DOIs
Publication statusPublished - May 2024

Austrian Fields of Science 2012

  • 106045 Theoretical biology

Keywords

  • Antagonistic selection
  • Evolution of cognition
  • Evolutionary medicine
  • Evolutionary mismatch
  • Genetic evolution
  • Schizophrenia

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