Updates, clarifications, and corrections - Awais Aftab, 13 May 2025
Since publication of the post “Schizophrenia Is the Price We Pay for Minds Poised Near the Edge of a Cliff,” friends and readers have reached out to me to highlight various problems with this hypothesis. It is perhaps not surprising at all that scientific details are complicated and recent research findings have cast doubt on some older reports. As I understand it, high polygenicity of schizophrenia (hundreds and thousands of alleles are involved), mechanistic heterogeneity (there is no single mechanism), and schizophrenia alleles being under current negative selection or common variants being very weak are all compatible with the cliff-edged dynamics theorized. What would favor or disfavor cliff-edge dynamics rests on a) whether there is good evidence of positive selection of schizophrenia alleles in the evolutionary past and b) whether the weak size of common variants is better seen as evidence of very weak positive selection in those not affected or as a deleterious effect so weak that it flies under the radar of natural selection.
Here are some important updates, clarifications, and corrections.