WASHINGTON — 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 most likely reveals what goes wrong neurologically in a young person diagnosed with the devastating disorder.
The report 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 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 skeptic," 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.
The genes involved coat the neurons with "eat-me signals," said report 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, thinks the research represents an astonishing breakthrough.
"It's taking what has been a black box ... and letting us peak inside for the first time. And that is amazingly consequential," he said.
There have been hundreds of theories about this mental illness over the years, but one of the enduring mysteries has been how three prominent findings related to each other: the apparent involvement of immune molecules in the disorder, the age of its typical onset in late adolescence and early adulthood, and the thinning of gray matter seen in autopsies of patients.
"The thing about this result," said Harvard geneticist Steven McCarroll, the lead author, "is it makes a lot of other things understandable. To have a result to connect to these observations and to have a molecule and strong level of genetic evidence from tens of thousands of research participants, I think that combination sets (this research) apart."
A cure is not right around the corner.
"This is the first exciting clue, maybe even the most important we'll ever have, but it will be decades" before a true cure is found," Hyman said. "Hope is a wonderful thing. False promise is not."