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Each Family May Have Schizophrenia In Its Own Way

Genetic changes in signaling pathways in the brain may cause schizophrenia.
Genetic changes in signaling pathways in the brain may cause schizophrenia.

Schizophrenia runs in families, but scientists have been stymied in their efforts to nail down genetic changes that could be causing the often devastating mental illness.

By zeroing in on just one pathway in the brain, scientists say they've found genetic variations that are shared in families, and tend to cause specific symptoms.

Though scientists have known for decades that schizophrenia is often hereditary, they haven't been able to find one gene that causes it. Instead, they now think that it's caused by lots of genetic variations, and that not everyone with the disease has the same ones. It's as if people are being dealt cards from multiple decks, and the rules of the game are different for each person.

Some scientists have tried to solve this mystery by looking at all the cards in the deck, scanning the genes of large groups of people to look for clues. Others take a more tightly focused approach, picking one suit, or even one hand, to examine very closely.

Researchers at Johns Hopkins took the focused approach. They looked at genes controlling one pathway in the brain, called the neuregulin signaling pathway, and scanned those genes in 123 families with a history of schizophrenia. Some families did have many more variations in their neuregulin genes. And the people in those families who had schizophrenia were more likely to have hallucinations, one symptom of the disease.

By contrast, other families didn't have neuregulin gene variations. And their family members with schizophrenia had different symptoms. They had more cognitive impairment, but fewer hallucinations.

The findings suggest that schizophrenia could be caused by genetic changes in just one pathway, the researchers say. The pathways could differ among patients, but be similar among families. Having more genetic variations on a critical pathway could explain why one family member has schizophrenia while another does not.

Identifying patients who have similar symptoms and genetic variations "would provide a leg up for the development of new meds," Ann Pulver, a psychiatric epidemiologist at Johns Hopkins University School of Medicine and a co-author of the study, said in an email. And it might also be used to figure out which existing medications are best for individual patients.

This is a case where more research really does need to be done to zoom in even closer on genetic regions of interest, Pulver and her colleagues say.

But other potential pathways for schizophrenia have been identified, and gene-scanning tools are becoming much more powerful, so that those sorts of studies may soon be feasible.

Schizophrenia affects about 1 percent of the population.

This study was published today in Translational Psychiatry.

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