Schizophrenia: Single-cell analysis sheds light on its intricate molecular biology

Scientists from several American research centers have carried out the largest single-cell analysis in the brains of people with schizophreniaachieving a map of how the geneswhich are known to increase the risk of suffering from this mental disorder severe, they affect specific cells of the brain.

The journals Science, Science Translational Medicine and Science Advances publish this Thursday more than a dozen articles from the Consortium ‘PsychENCODE’, 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, due to 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 revealed time windows ‘critics’ during brain development, where these genes may further influence the disease process.

Several of the studies published today focus on schizophrenia. Researchers at McLean Hospital and Mount Sinai discovered new and ‘important’ data on the molecular biology of this disorder.

Their research represents the largest single-cell analysis carried out to date in the brains of people with schizophrenia and a population-scale map of the regulatory components of the brain, the first of its kind, which provides ‘fundamental knowledge’ about the pathogenesis of mental disorders. according to the authors.

“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 diseases, and we believe that with our latest research we have significantly advanced this field.”

These works discover which types of cells express genes associated with the risk of schizophrenia differently, what biological functions are affected within those cells and which transcription factors – proteins that participate in the regulation of 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 analyzes included more than 468,000 cells.

They discovered ‘unprecedented knowledge’ on the cellular basis of schizophrenia, linking genetic risk factors with specific neuronal populations.

Specifically, they saw that excitatory neurons emerged as the most affected cell group, with transcriptional changes involving neurological development 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,” W. Brad Ruzicka, from McLean Hospital, points out 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.

It may interest you

• One in 160 children has ASD: the characteristics
• They develop an algorithm that detects schizophrenia from a fingerprint
• Scientists connect the childhood microbiome with the development of autism and ADHD