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UK Team Shows That Schizophrenia, Bipolar Disorder, Share Genetic Roots

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A team of British researchers has shown that schizophrenia and bipolar disorder share genetic roots that stem from reduced expression of genes responsible for myelin development.

Sabine Bahn from the University of Cambridge, UK, and colleagues investigated oligodendrocyte-specific and myelination-associated gene expression in schizophrenia and bipolar disorder. (Oligodendrocytes produce the myelin sheaths, which insulate nerve cells. Myelin, which is 80 percent lipid and 20 percent protein, enables electrical impulses to travel down the axon.)

The investigators used PCR and microarray analysis to compare gene expression in the preserved brains of 45 individuals — 15 with confirmed schizophrenia, 15 who had had bipolar disorder, and a control group of 15 brains from people who had neither disorder.

The team identified “a clear reduction” of key oligodendrocyte-related and myelin-related genes in schizophrenia and bipolar patients, while gene-expression changes for both disorders displayed a “high degree of overlap.” Additionally, there was “strong correlation” with results obtained through microarray analysis compared with those gathered by quantitative PCR.

“We believe that our results provide strong evidence for oligodendrocyte and myelin dysfunction in schizophrenia and bipolar disorder,” Bahn said in a statement. Expression profiles of most known oligodendrocyte-specific and myelin-associated genes were “greatly reduced,” he went on, and several transcription factors that coordinate myelin gene expression showed “corresponding alterations.”

“The high degree of correlation between the expression changes in schizophrenia and bipolar disorder provide compelling evidence for common pathophysiological pathways that may govern the disease phenotypes of schizophrenia and bipolar disorder,” Bahn wrote in her study, which appears in this week’s issue of The Lancet.

In an accompanying commentary, Kenneth Davis, a researcher at the Mount Sinai School of Medicine in New York writes that “the observation that at least some myelin-related gene-expression deficits are common between individuals with schizophrenia and bipolar disorder is intriguing” because both diseases, which account for about 2 percent of the population, have different symptom profiles and are treated against different neurotransmitter systems.

Bahn’s team has since finished a similar, though much larger, study that looked at 23,000 genes from 50 schizophrenic brains, 50 bipolar brains, and 50 controls. Results from this research lead Bahn to speculate that myelin changes are “probably secondary” to “some more fundamental disease process because oligodendrocytes … are particularly vulnerable, because they’re metabolically very active.”

Bahn told SNPtech Reporter that her research has already prompted calls from drug makers, namely GlaxoSmithKline and Merck, which both expressed interest in using the data to develop a molecular diagnostic. She has received “quite a bit of interest from the pharmaceutical industry,” she said.

However, said she might use her data to help develop such a diagnostic in-house.

— KL

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