Researchers have found variations in a small number of genes that appear to dramatically increase the likelihood of developing schizophrenia in some people.
The discovery could one day lead to advances in diagnosis of, and therapy for, the disease, according to the lead author of the study, Tarjinder Singh, of the Broad Institute at MIT and Harvard, which led an effort that involved years of work by dozens of research institutions worldwide.
“This is the biological clue that leads to better therapies,” Singh said in an interview. “But the key thing is, we haven’t had any meaningful clues for the longest time.”
Ken Duckworth, chief medical officer for the National Alliance on Mental Illness, a nationwide advocacy group, said the study is an important development in the neuroscience that underlies schizophrenia. But he said it is difficult to predict how soon such basic research would pay off for people living with the disease.
“This is a big step forward for science that may pay a long-term return for people with schizophrenia and the people who live with them,” Duckworth said. But, he said, “if this is a 17-inning game and they’ve gotten us from the first to the second inning, how does this help someone today?”
Less than 1 percent of the U.S. population is believed to have schizophrenia, which is generally treated with an array of powerful antipsychotic medications. The disease reduces life expectancy by about 15 years, according to the new research.
Scientists have long recognized a hereditary component to the disease, along with other factors such as environment.
The work of isolating these genes could not have been accomplished even 10 or 15 years ago, Singh said, before the sequencing of the human genome and the spread of technology that allows such genetic detective work to be conducted in laboratories around the world.
The current effort involved sequencing the exomes — the functional part of the larger human genome — of 24,248 people with schizophrenia and 97,322 others without the disease.
The results implicated very rare variations in 10 genes and hinted at the involvement of 22 more, according to the research. Some of the genes also appear to be involved in autism spectrum disorder and other intellectual development disorders, Singh said.
The mutations in the genes considered most likely to lead to schizophrenia appear to disrupt one way neurons in the brain communicate across synapses, the tiny spaces between them. Problems with that “glutamatergic system” have been suspected in schizophrenia.
“Despite this progress, it is clear that we are still in the early stages of gene discovery,” the authors wrote. “ … These emerging genetic findings will serve in part to direct and motivate mechanistic studies that begin to unravel disease biology.”