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Schizophrenia Study, Plus a Little Cash, Jump-Start Psychiatric Research

Image: Summer student Lydia Emerson at Broad Institute in Cambridge, Mass.

Summer student Lydia Emerson at the Broad Institute in Massachusetts. The institute just won a $650 million private grant to study mental illness. Kelly Davidson Photography / Broad Institute

A big study looking at the genetics of schizophrenia, and a giant, $650 million grant to push the work forward, have given a huge jump start to research into psychiatric disease, experts said Tuesday.

The study found more than 100 different places in the genes that might cause the symptoms of schizophrenia. This changes the understanding of how schizophrenia, and perhaps other types of mental illness, get started in the brain, the experts said. That can lead to new treatments in an area where the main drugs are decades old.

“For the first time we can start to see the underlying biological basis of the disease,” the Broad Institute’s co-founder Eric Lander told a news conference.

And to help pay for work going forward, philanthropist and businessman Ted Stanley said he has given the Cambridge, Massachusetts-based Broad Institute $650 million.

“This kind of critical mass will make all of the difference.”

Researchers who got the money were practically giddy. “It’s just amazing. It’s a historic commitment,” Lander said. “What we always lacked to make progress was insight into the molecular causes. I think the time has come due, in no small part, to this gift from the Stanleys. This kind of critical mass will make all of the difference.”

Stanley, 83, has already given the Broad Institute $175 million to start a mental health center in his name. He said he got interested in mental health research because his son, Jonathan, was diagnosed with bipolar disorder as a college junior. “After a couple of awful years for our son and ourselves he went on the have a totally normal life for almost 30 years since,” Stanley said in a prepared video statement.

“I am devoting my personal wealth to this goal. But it will take all of us -- philanthropists, government funding agencies, scientists, patients, and families -- working together to achieve it.”

For the study, published in the journal Nature, a team of 300 international scientists studied nearly 37,000 people with schizophrenia, comparing their DNA to that of 113,000 people without mental illness. They did what’s called a genome wide association study – which involves looking at all the DNA.

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They found 128 different genetic changes at 108 spots in the genome that seem to be different in people with schizophrenia. And 83 of these were changes no one had associated with schizophrenia before. Some appear to affect neurotransmitters, the brain’s message-carrying chemicals.

New genes mean new targets. Scientists can now begin to design drugs that might modify the errors that cause the worst symptoms of schizophrenia, such as psychosis.

“The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases,” said Michael O’Donovan of the Center for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine.

"The wealth of new findings have the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years,” added O’Donovan, who helped lead the study.

Schizophrenia affects one in 100 people. Most experts believe it's caused by a combination of a genetic susceptibility and something affecting a person from the outside. Studies link schizophrenia with everything from having flu during pregnancy to smoking pot.

“I am devoting my personal wealth to this goal."

It is mostly treated using antipsychotic drugs, ranging from the first antipsychotic, Thorazine, approved in 1954, to a new generation called atypical antipsychotics, such as Abilify and Risperdal.

“Every anti-psychotic drug on the market today fundamentally has the same mechanism of action,” said Dr. Steve Hyman, a former director of the National Institute of Mental Health who now directs the center Stanley pays for at Broad.

The drugs can cause immune system changes that leave a person vulnerable to infection, weight gain and a very irritating side effect called tardive dyskinesia, which causes uncontrollable muscle movements. The drugs can also interact with other medications, and drugs that help one patient do little or nothing for another.

So often patients refuse to take the drugs.

Having new understandings of what causes the symptoms may help in the design of better drugs that don’t have the same side effects.

“We are poised for real advances here. We are not just going to wring our hands. We are going to do something,” said Dr. Francis Collins, director of the National Institutes of Health.

“We are going to illuminate the biology behind these conditions,” said Lander. “If we know the biological causes, we can begin to dispel the stigma around people battling mental illness, and rigorously pursue better treatments that will transform patients’ lives.”