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 Centre for Psychiatric Research at the Broad Institute at the Massachusetts Institute of Technology. Hyman, a former director of the National Institute of Mental Health, calls it "the most significant mechanistic study about schizophrenia ever." "I'm a crusty, old, curmudgeonly skeptics," he said. "But I'm almost giddy about these findings."
The researchers, chiefly from the Broad Institute, Harvard Medical School and Children's Hospital in Boston, 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 synapses for removal and that pruning goes out of control. The result is an abnormal loss of gray matter.
Scientists have found that a person's risk of schizophrenia increases 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.
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 founding director of the Broad Institute, 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 geneticist Steven McCarroll analysed data from some 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 Genome Consortium.
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