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Scientists find strongest genetic influence on schizophrenia

Excess expression of the genomic protein C4 in the brain during the teenage years destroys connections and increases the risk schizophrenia.
By Stephen Feller   |   Jan. 27, 2016 at 5:00 PM

BETHESDA, Md., Jan. 27 (UPI) -- Scientists found a gene linked to schizophrenia may interfere with the development of communications infrastructure in the brain during the teenage years, leading to the development of the psychological disorder later in life.

Researchers at Harvard Medical School in a large review of genomes and brains found a suspect version of the complement component 4, or C4, gene is found more often in people with schizophrenia than in those without.

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The gene also has a role in the immune system, leading researchers to note that drugs designed to counteract C4 are already in development for other uses. The protein is also known to play a role in "pruning," a process by which excess, no longer needed neurons are eliminated. Previous research has found fewer connections between neurons, called synapses, in the brains of people with higher levels of C4.

"Since schizophrenia was first described over a century ago, its underlying biology has been a black box, in part because it has been virtually impossible to model the disorder in cells or animals," said Dr. Steve McCarroll, of the Broad Institute and Harvard Medical School, in a press release. "The human genome is providing a powerful new way in to this disease. Understanding these genetic effects on risk is a way of prying open that block box, peering inside and starting to see actual biological mechanisms."

For the study, published in the journal Nature, researchers analyzed the genomes of 65,000 people and studied 700 postmortem brains, finding the significance of a greater presence of the C4 gene and another form of it called C4A.

Researchers found the more C4 protein was switched on in their brains, the more likely they were to develop schizophrenia. Testing with mice revealed the more the C4 gene is turned on during brain development, the more synapses were eliminated.

Future research will focus on suppressing the work of extra C4 to prevent the elimination of too many synapses during development -- during the teen years, in the case of humans.

"This study marks a crucial turning point in the fight against mental illness. It changes the game," added acting NIMH director Bruce Cuthbert, Ph.D. "Thanks to this genetic breakthrough, we can finally see the potential for clinical tests, early detection, new treatments and even prevention."

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