Prioritization of potential causative genes for schizophrenia in placenta, 2023, Weinberger et al

Prioritization of potential causative genes for schizophrenia in placenta
https://www.nature.com/articles/s41467-023-38140-1


Abstract

Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.


Conclusion

In conclusion, our findings, while not detracting from the importance of gene expression in brain for schizophrenia risk, reveal a larger picture that includes placenta: both placenta and brain might contribute to early and reversible trajectories of risk for the disorder, but most research on brain development has been exclusively focused on the brain. Neglecting the investigation of placental mechanisms of risk may miss relevant opportunities for prevention.

 

Easier-to-digest article: https://scitechdaily.com/placenta-not-brain-groundbreaking-study-shifts-the-schizophrenia-narrative/.

A new study conducted by the Lieber Institute for Brain Development suggests that the risk of schizophrenia is largely due to the role of over 100 associated genes in the placenta, rather than in the developing brain.

This contradicts the century-old assumption held by scientists that genes linked to schizophrenia were primarily, if not entirely, related to the brain. The recent research, published in Nature Communications, highlights a more substantial involvement of the placenta in the origin of the illness than previously recognized.

“The secret of the genetics of schizophrenia has been hiding in plain sight—the placenta, the critical organ in supporting prenatal development, launches the developmental trajectory of risk,” says Daniel Weinberger, M.D., senior author of the paper and Director and CEO of the Lieber Institute for Brain Development, located on the Johns Hopkins medical campus in Baltimore. “The commonly shared view on the causes of schizophrenia is that genetic and environmental risk factors play a role directly and only in the brain, but these latest results show that placenta health is also critical.”
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The paper also identifies several genes in the placenta that are causative factors for diabetes, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder, or ADHD. The scientists, however, found far more genetic associations with genes for schizophrenia than for any of these other disorders.
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The researchers also uncovered concerning results about COVID-19 pregnancies. The scientists studied a small sample of placentas from mothers who had COVID-19 during pregnancy and found the schizophrenia genes for placenta risk were dramatically activated in these placentas. The finding indicates that COVID-19 infection during pregnancy may be a risk factor for schizophrenia because of how infection affects the placenta. Lieber Institute scientists are pursuing this possibility with NIH-funded research examining COVID-19 placentas to learn more.
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Wessely famously whined that if ME can be considered a disease, than so should schizophrenia. Dude really has incredible talent as a reverse Cassandra, you can set your watch to the opposite of what he says.

 

I mean, most people would consider schizophrenia a disease. A very severe and cruel one, at that. There is a reason it was called "Dementia precox" back in the days, before doctors realized that you could just fake results with psychology and social therapies, and then use those fake results to justify your lack of results. Doesn't really make sense, but hey the doctor is always right.