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Science

Risk of developing schizophrenia rises the farther north you go in Finland

Researchers have localized a significant schizophrenia gene in remote parts of northern Finland. The risk of developing the illness is three times higher there than elsewhere.

The risk of developing schizophrenia is about one percent - around the globe. But in the northeast of Finland, the mental disorder occurs three times more frequently than in other parts of the world.

The northern regions are home to remote rural communities, which were founded by about 40 families in total, says Aarno Palotie, a geneticist at the Institute for Molecular Medicine Finland in Helsinki. He says the communities have a very specific genetic background.

"We saw this as a research opportunity to try to understand schizophrenia better," says Palotie.

So Palotie and his colleagues traveled to these northeastern parts in search of genes linked to schizophrenia. And they found one while studying the local population: the gene TOP3β.

The TOP3β encodes a protein that acts on the genetic material inside a cell. And it's thought to be responsible for the faulty development of the brain in those who took part in the study.

"We wouldn't have found this gene if we had studied people in large cities with mixed ethnic origins," Palotie told DW.

Common symptoms of schizophrenia include hallucinations, delusions, or disorganized speech and thinking. If diagnosed early in life, patients can often manage hallucinations and prevent any social dysfunction.

A woman suffering from mental illnesses. Foto: KAISA SIREN / LEHTIKUVA dpa - Report

People suffering from schizophrenia often hallucinate or suffer delusions

Help from abroad

"We really had to find out why this gene was associated with schizophrenia," says Palotie. "And all of a sudden we got this email."

Biochemists at the University of Würzburg in Germany had been researching the TOP3β for quite some time. When they read about Palotie's discovery they were thrilled.

"It was a perfect match," Georg Stoll of Würzburg University told DW. "Until then we had only suspected that the gene was linked with schizophrenia, but we couldn't be sure".

But when the two research teams got together to compare data, they knew they had the beginnings of something solid. Their combined research showed that if the protein TOP3β is missing inside a cell, the risk of developing schizophrenia rises dramatically.

A little piece in the puzzle

TOP3β is not the first to have been found - and it's by no means the only risk factor.

Researchers have discovered several genes and even regions in the genetic material that influence whether a person develops schizophrenia or not.

Some of the genes group together on chromosome 22. The researchers say that the loss of a gene on chromosome 22 as much as doubles the risk of developing schizophrenia, or another form of cognitive impairment. It's thought that some of the genes may even join forces, making a person more prone to the schizophrenia.

But the biochemical drivers behind a protein's actions are often unknown. The same is true for TOP3β.

What's known is that the protein is located in the nucleus of the cell and is involved in gene regulation.

"We know in which cellular pathway the protein acts in the cell," says Stoll. "So at least we know where to look."

The researchers now want to find out exactly what goes wrong in the cell when the protein is missing and why this may cause schizophrenia.

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Two mental illnesses linked together

There is a second element that makes this case especially interesting.

The TOP3β gene is part of a larger gene group. One of its "partner" genes is the FMRP, which also affects a mental illness, the so-called Fragile X syndrome, a mental retardation and form of autism.

In the spectrum of mental disorders, schizophrenia and autism are opposites.

"So we believe that whichever of the two proteins is missing inside a cell, it will cause either the one or the other extreme," Stoll says.

Both diseases may be linked together genetically. And recent studies confirm the theory.

"Our unpublished data show that the Fragile X pathway is an important risk component for schizophrenia," says Palotie. This means that people who have Fragile X syndrome could be at a higher risk of developing schizophrenia as well.

A possible target for medication

So why is it important to understand the genes that influence an illness?

For one, people could have themselves tested for genetic risk factors. That said, Stoll doubts whether this is a good idea. Schizophrenia is different from many other hereditary diseases - if you're missing the TOP3β gene, it doesn't necessarily mean you'll develop schizophrenia.

"Yes, the risk is definitely higher," says Stoll, "but that doesn't automatically make you schizophrenic."

Then there's further research into medication. Both Stoll and Palotie agree that understanding the genes involved in schizophrenia will make it easier to develop medicines to treat the condition. Researchers may even be able to develop a compound that will help replace the missing protein.

But here again, Stoll advises caution. "This is a step into the right direction," he says, "it doesn't yet mean we can heal schizophrenia."

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