University Of Toronto , 11/13/2002

Scientists at U of T have discovered the first "risk gene" for schizophrenia found in the general population.

An uncommon variation of a gene called Nogo, when inherited from both parents, increases the risk of developing schizophrenia, says a study to be published in Molecular Brain Research Nov. 15. Previous findings about other risk genes for the disease were restricted to specific ethnic groups.

"Finding a risk gene in the general population - the first finding of this type internationally - opens the door to discovering new and related risk genes. Now scientists will know where to look for related genes," says pharmacology and psychiatry professor Philip Seeman. "This will help in diagnosis and potentially in the design of new medications for treatment of this terrible disease," adds Seeman who worked on the study with psychiatry professor Teresa Tallerico, lead author and pharmacology graduate student Gabriela Novak and undergraduate student David Kim.

The study shows that one in five people with schizophrenia has this risk gene. Researchers found that 17 of 81 individuals with schizophrenia - 21 per cent - had inherited the uncommon Nogo variant gene from both parents. In a control group of individuals without schizophrenia, only three per cent had inherited the gene from both parents. People can inherit the variant Nogo gene from just one parent but there's a schizophrenia risk only when this gene is inherited from both parents. The gene does not suggest a diagnosis for schizophrenia but rather an increased predisposition to the illness.

One of the Nogo gene's functions is to produce proteins that inhibit the growth of nerve endings in the brain. Unlike the common form of Nogo, the variant gene has three extra chemical bases, known as CAA, in a region of the gene that regulates protein production. The researchers found that activity of the Nogo genes was higher in the post-mortem brain samples of individuals with schizophrenia. It is possible that these extra CAA bases lead the variant Nogo gene to produce more proteins, thereby reducing the number of nerve endings in regions of the brain associated with schizophrenia symptoms, Seeman says. However, more research is needed to confirm this.

"This study adds to the rapidly evolving theory that, in the brain of those who suffer from schizophrenia, the nervous system develops in a slightly altered fashion leading to the onset of symptoms such as hallucinations and delusions in young adulthood," says Seeman.

Although the cause of schizophrenia is not known, the treatment of the symptoms has been well-established since the 1970s. Antipsychotic medication is used to block the action of dopamine, an adrenaline-like chemical transmitter in the nervous system that becomes overactive in people with schizophrenia.

"This finding of a risk gene in the general population could lead to the development of medications outside the dopamine system, perhaps targeting the protein produced by the gene," suggests Seeman.

The study was supported by the National Alliance for Research on Schizophrenia and Depression, the Eli Lilly Research Fellowship in Women's Mental Health, the Stanley Foundation Scholars Mentors Program of the National Alliance for the Mentally Ill, the Canadian Institutes for Health Research, the Ontario Mental Health Foundation and the National Institute on Drug Abuse. Professor Tallerico is an Essel Investigator of the National Alliance for Research on Schizophrenia and Depression (NARSAD) and Professor Seeman is a Janice Lieber Investigator of NARSAD.

The University of Toronto, Canada's leading research university with 60,000 students, is celebrating its 175th anniversary in 2002.