Schizophrenia, Bipolar Disorder May Share Malfunctioning Gene

Could two mental illnesses with quite different symptoms—schizophrenia and bipolar disorder—share some of the same genetic flaws? Mounting evidence bolsters just such a hypothesis.

A protein known to interact with dopamine receptors was found to demonstrate abnormally high activity in the prefrontal cortex region of brains of deceased persons who had been diagnosed with schizophrenia and of deceased individuals who had had bipolar disorder (Psychiatric News, February 7).

In May Elliot Gershon, M.D., a professor of psychiatry and human genetics at the University of Chicago, and coworkers reported that two genes on chromosome 13 with undetermined functions appeared to increase the risk for both schizophrenia and bipolar disorder.

And now Sabine Bahn, M.D., Ph.D., a clinical lecturer in psychiatry at the University of Cambridge in England, and colleagues have found that some genes that do not express themselves properly in the brains of schizophrenia patients also do not express themselves correctly in the brains of bipolar disorder patients. The genes in question help make the myelin sheaths that insulate brain nerve cells. The findings were published in the September 6 The Lancet.

A number of studies from various scientists had already suggested that certain genes that make nerve-cell myelin are abnormally expressed—that is, engage in abnormal messenger RNA transcription—in the brains of schizophrenia patients. So Bahn and her team decided to see whether this might be the case for brains from bipolar disorder patients as well.

To explore this, they took prefrontal cortex material from 15 deceased persons who had had schizophrenia, from 15 who had had bipolar disorder, and from 15 who had had neither illness. They then used three high-technology techniques to measure the expression of myelin-producing genes present in the brain material for the three groups. The techniques were differential display polymerase chain reaction, real-time quantitative polymerase chain reaction, and microarray analysis. (Differential display PCR is a method whereby two populations of RNA are compared. Real-time quantitative PCR is a method that measures specific amounts of DNA that have been reverse-transcribed from RNA. Microarray analysis is a method that allows for the measurement of mRNA in a sample on a massive scale.)

The researchers found a highly statistically significant reduction in the expression of a number of myelin-producing genes in schizophrenia brain material compared with control brain material.

They also found a highly statistically significant reduction in the expression of a number of myelin-producing genes in bipolar brain material compared with control brain material.

“The high degree of correlation between expression changes in schizophrenia and bipolar disorder provides compelling evidence for common pathophysiological pathways that may govern the disease phenotypes of schizophrenia and bipolar affective disorder,” the researchers concluded.

“The observation that at least some myelin-related gene-expression deficits are common between individuals with schizophrenia and bipolar disorder is intriguing because schizophrenia and bipolar disorder have different symptom profiles and require treatments based on quite different neurotransmitter systems.” So wrote Kenneth Davis, M.D., chair of psychiatry, and Vahram Haroutunian, Ph.D., an associate professor of psychiatry and neurobiology at Mount Sinai School of Medicine in New York City, in an editorial accompanying The Lancet report.

“I have seen the study [report from Bahn and team],” Gershon told Psychiatric News. “It is quite important. . . .”

In contrast—and not surprisingly—increasing evidence also shows that the genes underlying schizophrenia are not always those that underlie bipolar disorder.

For example, Bahn and her colleagues reported in 2002 that three genes that make lipoproteins (which in turn play a central role in cholesterol transport) appear to be overly expressive in the brains of persons with schizophrenia, but not in the brains of persons with bipolar disorder (Psychiatric News, April 19, 2002).

The recently reported study by Bahn and her team was funded by the National Alliance for Research on Schizophrenia and Depression, Britain’s Biotechnology and Biological Sciences Research Council, and the Stanley Medical Research Institute.

A summary of the study report, “Oligodendrocyte Dysfunction in Schizophrenia and Bipolar Disorder,” is posted on the Web at www.thelancet.com. ▪