Scientists open the ‘black box’ of schizophrenia with dramatic genetic discovery
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."
"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 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.
More than 25 million people around the globe are affected by schizophrenia, according to the World Health Organization, including 2 million to 3 million Americans. Highly hereditable, it is one of the most severe mental illnesses, with an annual economic burden in this country of tens of billions of dollars.
Two of my best friends growing up, brothers, ended up with schizophrenia in early adulthood. They were normal kids, one very smart too. Unfortunately it sounds like maybe the process is not reversible. Hopefully it could be preventable someday though. They found a gene that puts you at high risk.
The study offers a new approach to schizophrenia research, which has been largely stagnant for decades. Most psychiatric drugs seek to interrupt psychotic thinking, but experts agree that psychosis is just a single symptom -- and a late-occurring one at that. One of the chief difficulties for psychiatric researchers, setting them apart from most other medical investigators, is that they can't cut schizophrenia out of the brain and look at it under a microscope. Nor are there any good animal models.
All that now has changed, according to Stevens. "We now have a strong molecular handle, a pathway and a gene, to develop better models," he said.