I am so glad you are getting good comments from experts, Awais. However, some seem to think that vulnerability to a disorder that results from a cliff edged fitness function implies selection for alleles that increase the risk of schizophrenia or that there should be alleles with strong effects. The distinctiveness of cliff edge explanations is that the alleles that influence vulnerability should be net neutral re fitness as a result of epistasis and developmental variation that influences the position of the cliff for an individual, consistent with the massive polygenicity and tiny effects from each allele with mostly purifying selection. See Mitteroecker, P., & Merola, G. P. (2024). The cliff edge model of the evolution of schizophrenia: Mathematical, epidemiological, and genetic evidence. Neuroscience & Biobehavioral Reviews, 160, 105636. https://doi.org/10.1016/j.neubiorev.2024.105636
The reason I have put this explanation on hold is that it does require some specific TRAIT whose increasing values yield rapidly increasing fitness that then collapses if the values go too high. I can't see such a trait in the case of schizophrenia. I think cliff edge effects are likely to be important mostly in cases where there has been strong selection on both sides of a tradeoff, as posited by Steve Frank in Frank, S. A. (2023). Disease from opposing forces in regulatory control. Evolution, Medicine, and Public Health, 11(1), 348–352. https://doi.org/10.1093/emph/eoad033
Also, my confidence that a wrenching transition offers a better explanation comes from new data finding that alleles that increase risk are older while those that reduce risk are newer. I would love to hear what geneticists make of these findings.
Liu, C., Everall, I., Pantelis, C., & Bousman, C. (2019). Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles. Frontiers in Genetics, 10, 389. https://doi.org/10.3389/fgene.2019.00389
replicated by
González-Peñas, J., De Hoyos, L., Díaz-Caneja, C. M., Andreu-Bernabeu, Á., Stella, C., Gurriarán, X., Fañanás, L., Bobes, J., González-Pinto, A., Crespo-Facorro, B., Martorell, L., Vilella, E., Muntané, G., Molto, M. D., Gonzalez-Piqueras, J. C., Parellada, M., Arango, C., & Costas, J. (2023). Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy. Scientific Reports, 13(1), 15500. https://doi.org/10.1038/s41598-023-42578-0
Did you already and can you understand like some people always have that dinosaur fossils alone, being millions of years old, disprove the legitimacy of any and all of those fake, man-made political labels, books, symbols, and buildings? Can you understand how and why electronic voting machines have never been valid? Has anyone pointed out to you what a "semite" is even? Naturally, people with sound minds will and should continue educating others about those already-long-known realities alone.
Dr. Aftab, P”dr.Kiaxi, Thomas Reilly, Sofia Jeppsson, Nils Wendel, and all,
Hello. Thank you for learning and sharing the best truth you can too on mental health. What mental illnesses are you aware of that can come from inbred humans? We ask because more and more people are becoming aware of these major unprosecuted illegal private banker crimes and psyops on people for a long time now. An example that people have been pointing out for years is these illegal private bankers in America and elsewhere, whatever and whoever they are:
Doctor, I admire your courage/shake my head at your foolhardiness for plunging into this currently unanswerable question.
What surprises me about schizophrenia is the fact that while the genes that produce it are manifold, the phenotype of the resulting illness is surprisingly uniform.
Ian Hacking wrote that the "typical schizophrenic" of the early twentieth century was pretty different from the "typical schizophrenic" of the late twentieth century. How a disorder typically manifests tend to change over time; testament to how deeply cultural beings we are.
Also, what strikes me again and again, since I work a lot with other academics with various mental health diagnoses, is how incredibly heterogenous pretty much every diagnostic group is. This goes for schizophrenia and schizo-spectrum disorders too. Even setting the spectrum aside, zooming in on schizophrenia proper, so to speak, you find plenty of variation. Anecdotally, I personally know one philosophy professor and one computer programmer with schizophrenia. And looking at quantitative research, the AVERAGE schizophrenia patient has marked cognitive decline over time, but there's still a lot of variation among individuals.
Moreover, going back a few decades, psychiatry didn't have one diagnosis of schizophrenia, but several diagnoses of paranoid schizophrenia, hebephrenic schizophrenia, and a few others. Later, it was merged to one diagnosis. You'd think that if schizophrenia was really uniform, it would have been just one diagnosis all along.
I am so glad you are getting good comments from experts, Awais. However, some seem to think that vulnerability to a disorder that results from a cliff edged fitness function implies selection for alleles that increase the risk of schizophrenia or that there should be alleles with strong effects. The distinctiveness of cliff edge explanations is that the alleles that influence vulnerability should be net neutral re fitness as a result of epistasis and developmental variation that influences the position of the cliff for an individual, consistent with the massive polygenicity and tiny effects from each allele with mostly purifying selection. See Mitteroecker, P., & Merola, G. P. (2024). The cliff edge model of the evolution of schizophrenia: Mathematical, epidemiological, and genetic evidence. Neuroscience & Biobehavioral Reviews, 160, 105636. https://doi.org/10.1016/j.neubiorev.2024.105636
The reason I have put this explanation on hold is that it does require some specific TRAIT whose increasing values yield rapidly increasing fitness that then collapses if the values go too high. I can't see such a trait in the case of schizophrenia. I think cliff edge effects are likely to be important mostly in cases where there has been strong selection on both sides of a tradeoff, as posited by Steve Frank in Frank, S. A. (2023). Disease from opposing forces in regulatory control. Evolution, Medicine, and Public Health, 11(1), 348–352. https://doi.org/10.1093/emph/eoad033
Also, my confidence that a wrenching transition offers a better explanation comes from new data finding that alleles that increase risk are older while those that reduce risk are newer. I would love to hear what geneticists make of these findings.
Liu, C., Everall, I., Pantelis, C., & Bousman, C. (2019). Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles. Frontiers in Genetics, 10, 389. https://doi.org/10.3389/fgene.2019.00389
replicated by
González-Peñas, J., De Hoyos, L., Díaz-Caneja, C. M., Andreu-Bernabeu, Á., Stella, C., Gurriarán, X., Fañanás, L., Bobes, J., González-Pinto, A., Crespo-Facorro, B., Martorell, L., Vilella, E., Muntané, G., Molto, M. D., Gonzalez-Piqueras, J. C., Parellada, M., Arango, C., & Costas, J. (2023). Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy. Scientific Reports, 13(1), 15500. https://doi.org/10.1038/s41598-023-42578-0
Dr. Aftab and all,
Did you already and can you understand like some people always have that dinosaur fossils alone, being millions of years old, disprove the legitimacy of any and all of those fake, man-made political labels, books, symbols, and buildings? Can you understand how and why electronic voting machines have never been valid? Has anyone pointed out to you what a "semite" is even? Naturally, people with sound minds will and should continue educating others about those already-long-known realities alone.
Michael
🦈
Dr. Aftab, P”dr.Kiaxi, Thomas Reilly, Sofia Jeppsson, Nils Wendel, and all,
Hello. Thank you for learning and sharing the best truth you can too on mental health. What mental illnesses are you aware of that can come from inbred humans? We ask because more and more people are becoming aware of these major unprosecuted illegal private banker crimes and psyops on people for a long time now. An example that people have been pointing out for years is these illegal private bankers in America and elsewhere, whatever and whoever they are:
https://drive.proton.me/urls/G6TKNMCM5W#iXcuPRX385i9
Thank you,
Michael
🦖
Doctor, I admire your courage/shake my head at your foolhardiness for plunging into this currently unanswerable question.
What surprises me about schizophrenia is the fact that while the genes that produce it are manifold, the phenotype of the resulting illness is surprisingly uniform.
Is it? Surprisingly uniform?
Ian Hacking wrote that the "typical schizophrenic" of the early twentieth century was pretty different from the "typical schizophrenic" of the late twentieth century. How a disorder typically manifests tend to change over time; testament to how deeply cultural beings we are.
Also, what strikes me again and again, since I work a lot with other academics with various mental health diagnoses, is how incredibly heterogenous pretty much every diagnostic group is. This goes for schizophrenia and schizo-spectrum disorders too. Even setting the spectrum aside, zooming in on schizophrenia proper, so to speak, you find plenty of variation. Anecdotally, I personally know one philosophy professor and one computer programmer with schizophrenia. And looking at quantitative research, the AVERAGE schizophrenia patient has marked cognitive decline over time, but there's still a lot of variation among individuals.
Moreover, going back a few decades, psychiatry didn't have one diagnosis of schizophrenia, but several diagnoses of paranoid schizophrenia, hebephrenic schizophrenia, and a few others. Later, it was merged to one diagnosis. You'd think that if schizophrenia was really uniform, it would have been just one diagnosis all along.