Illustrative image of a person suffering from schizophrenia. (Illustration El Nuevo Diario)
EL NUEVO DIARIO, SCIENCE EDITORIAL.- Scientists from several American research centers have performed the largest single-cell analysis in the brains of people with schizophrenia to obtain a map of how genes known to increase the risk of suffering from this serious mental disorder affect specific brain cells .
This Thursday, the journals Science, Science Translational Medicine and Science Advances will publish more than a dozen papers from the ‘PsychENCODE’ consortium, created in 2015 and dedicated to elucidating the molecular mechanisms underlying schizophrenia, bipolar disorder and autism spectrum disorder.
These goals are challenging, among other things, due to the size and complexity of the human brain.
The largest genetic study of schizophrenia sheds light on its origins
Since the founding of the consortium, scientists have identified several hundred new risk genes for these mental disorders and revealed “critical” time windows during brain development when these genes can most influence the disease process.
Several studies published today focus on schizophrenia. Researchers at McLean Hospital and Mount Sinai have discovered “important” new data about the molecular biology of the disorder.
Their research represents the largest single-cell analysis to date of the brains of people with schizophrenia and a population-scale map of brain regulatory components, the first of its kind to provide “basic insights” into brain pathogenesis. mental disorders according to the authors.
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“We desperately need new avenues to develop treatments for schizophrenia and other serious mental illnesses,” says Panos Roussos in a statement from Mount Sinai Hospital.
According to Roussos, “we now have the technology and methodology necessary to delve deeper than ever into the biology of neuropsychiatric disease, and we believe that with our latest research we have advanced the field significantly.”
These works reveal which cell types express genes associated with the risk of schizophrenia differently, which biological functions are affected in these cells, and which transcription factors – proteins involved in DNA regulation – are important for these changes.
For the new study, the teams performed a comprehensive single-cell analysis of transcriptomic changes—which genes are expressed in which cells—in the human prefrontal cortex, examining postmortem brain tissue from 140 individuals in two independent cohorts. Their analyzes included more than 468,000 cells.
They discovered “unprecedented insights” into the cellular basis of schizophrenia, linking genetic risk factors to specific neuronal populations.
Specifically, they saw that excitatory neurons emerged as the most affected cell group, with transcriptional changes involving neurodevelopmental and synapse-related pathways.
The authors note that these results could pave the way for targeted interventions and personalized treatments for schizophrenia, potentially improving clinical outcomes for affected individuals.
“This knowledge will allow future treatments to be tailored to specific genes and cell types, as well as individuals with schizophrenia,” McLean Hospital’s W. Brad Ruzicka notes in another note.
The researchers are now working to extend these findings to other areas of the brain and to the molecular impact of other psychiatric diseases such as disorders.
