MADRID (EFE).— Scientists from several American research centers have conducted the largest single-cell analysis of the brains of people with schizophrenia, creating a map of how genes known to increase the risk of suffering from this serious mental disorder affect specific brain cells.
The journals “Science”, “Science Translational Medicine” and “Science Advances” have published more than a dozen articles from the “PsychENCODE” Consortium, created in 2015 and dedicated to elucidating the molecular mechanisms underlying schizophrenia, bipolar disorder and autism spectrum disorder.
These objectives are challenging, among other things, because of the size and complexity of the human brain.
Since the launch of the consortium, researchers have identified several hundred new risk genes for these mental disorders and have revealed “critical” time windows during brain development when these genes may most influence the disease process.
Several of the published studies focus on schizophrenia. Researchers at McLean Hospital and Mount Sinai have discovered “important” new data on the molecular biology of this disorder.
Their research represents the largest single-cell analysis to date of the brains of people with schizophrenia and a population-scale map of the brain’s regulatory components, the first of its kind, which provides “fundamental knowledge” regarding the pathogenesis of mental disorders, according to the authors.
“We desperately need new avenues for developing treatments for schizophrenia and other serious mental illnesses,” said Panos Roussos in a statement from Mount Sinai Hospital.
According to Roussos, “We now have the technology and methodology to delve deeper than ever before into the biology of neuropsychiatric diseases, and we believe that our latest research has significantly advanced this field.”
These studies are uncovering which cell types express genes associated with schizophrenia risk differently, what biological functions are affected within those cells, and which transcription factors—proteins involved in regulating DNA—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 analyses 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 implicating neurodevelopment and synapse-related pathways. The authors note that these results might 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 to individuals with schizophrenia,” notes W. Brad Ruzicka of McLean Hospital in another note.
Scientists are now working to extend these findings to other brain regions and the molecular impact of other psychiatric diseases, such as bipolar disorder.
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2024-07-02 13:36:56