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Brain cell insulation may be the key
By Hilary Thomson

A UBC researcher has made a breakthrough that promises new treatment for schizophrenia in the treatment of
schizophrenia patients.

Psychiatry Prof. Bill Honer has discovered that schizophrenia patients show a significant loss of myelin -- the material that surrounds and insulates brain cells and helps transmit messages within the brain -- compared to people without the disease. Using magnetic resonance imaging (MRI), he found there was particular loss of myelin in the frontal lobes of the brain that are the site of decision-making and memory functions. He believes the myelin abnormality could be a contributing factor in patients' slow recovery from the illness.

“These findings represent another window into the mechanism of schizophrenia and open up a whole new area for developing treatments,” says Honer, who holds the Jack Bell Chair in Schizophrenia and is a member of the Vancouver Coastal Health Research Institute. “Our current treatments can regulate the disease to some extent, but even with medication many patients are still impaired.”

This is the first study ever to focus specifically on myelin loss in living patients. Previous research has examined the general condition of white matter, the material in the central core of the brain that includes myelin and other components. Honer's work confirms in living patients what other researchers have recently discovered in gene studies using post-mortem samples.

The findings of the 1997-2001 study were reported recently in Molecular Psychiatry, a journal of the Nature Publishing Group.

Using MRI technology developed by UBC multiple sclerosis (MS) researchers, Honer and his research team looked at MRI scans of 30 patients with schizophrenia and compared them to a control group. The patients, who agreed to participate in the study, were being treated by research team member Dr. Sean Flynn at Riverview Hospital, a site of the Provincial Health Services Authority.

The scans showed a 12 per cent loss of myelin, a biological effect that may be compared to the appearance of frayed insulation around electrical wiring. Researchers don't know the cause of the abnormalities, however, they do know that they can impair synchronization of signals between brain cells, which could give rise to schizophrenia symptoms such as hallucinations, delusions and distorted thinking.

In a second part of the study, Honer looked at 13 post-mortem samples of brain tissue collected from hospitals around the world. He analyzed two proteins found in the cells that make myelin. One of these proteins was 33 per cent lower in brain samples from patients who had schizophrenia. The information complements the MRI findings and will further help scientists understand how brain cell communication is impaired among schizophrenia patients.

Honer cautions that abnormal myelin does not necessarily mean a patient will develop schizophrenia. Scientists haven't yet found a way to reverse myelin degradation, but drugs in development to treat MS patients -- who also suffer myelin loss -- may improve the condition in patients with schizophrenia.

Affecting an estimated one person in 100, schizophrenia most often develops in individuals aged 16-30 years. The mechanism of illness remains unclear. The disease affects women and men with equal frequency and often appears earlier in men. A biological disorder of the brain, schizophrenia is treated with a number of medications that help to balance complicated interrelated chemical systems of the brain. The medications can have serious side effects, however, ranging from drowsiness to loss of white blood cells. About 10 per cent of individuals with schizophrenia commit suicide.

“Schizophrenia is a tragic illness for both patients and their families and treatment hasn't changed much in 50 years,” says Honer. “These new avenues of research reinforce that this is a biological disorder and gives further hope for better treatments.”

Next steps in Honer's research program include studying how nerve cells communicate with cells that make myelin, looking at genetic variations in myelin and determining exactly how myelin loss affects function.

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