Monday, October 26, 2020

Scientists Open The ‘Black Box’ Of Schizophrenia With Dramatic Genetic Discovery

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For the first time, scientists have pinned down a molecular process in the brain that helps to trigger schizophrenia. The researchers involved in the landmark study, which was published Wednesday in the journal Nature, say the discovery of this new genetic pathway probably reveals what goes wrong neurologically in a young person diagnosed with the devastating disorder.The study marks a watershed moment, with the potential for early detection and new treatments that were unthinkable just a year ago, according to Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute at MIT.

 

 

Hyman, a former director of the National Institute of Mental Health, calls it “the most significant mechanistic study about schizophrenia ever.”The researchers, chiefly from the Broad Institute, Harvard Medical School and Boston Children’s Hospital, found that a person’s risk of schizophrenia is dramatically increased if they inherit variants of a gene important to “synaptic pruning” — the healthy reduction during adolescence of brain cell connections that are no longer needed.In patients with schizophrenia, a variation in a single position in the DNA sequence marks too many synapses for removal and that pruning goes out of control.

The result is an abnormal loss of gray matter.The genes involved coat the neurons with “eat-me signals,” said study co-author Beth Stevens, a neuroscientist at Children’s Hospital and Broad. “They are tagging too many synapses. And they’re gobbled up.”The Institute’s founding director, Eric Lander, believes the research represents an astonishing breakthrough. “It’s taking what has been a black box…and letting us peek inside for the first time. And that is amazingly consequential,” he said.The timeline for this discovery has been relatively fast. In July 2014, Broad researchers published the results of the largest genomic study on the disorder and found more than 100 genetic locations linked to schizophrenia.

Based on that research, Harvard and Broad geneticist Steven McCarroll analyzed data from about 29,000 schizophrenia cases, 36,000 controls and 700 post mortem brains. The information was drawn from dozens of studies performed in 22 countries, all of which contribute to the worldwide database called the Psychiatric Genomics Consortium.One area in particular, when graphed, showed the strongest association. It was dubbed the “Manhattan plotfor its resemblance to New York City’s towering buildings.

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