Friday, November 16, 2007

DISC1 Gene and Mental Illness

The latest issue of Science has a fascinating update on research into the role genes play in brain development. It's titled "BEHAVIORAL GENETICS: Evidence Linking DISC1 Gene to Mental Illness Builds" by Jean Marx. Here are a few excerpts:

Every clan has its misfits, but an extended family in northern Scotland is extraordinary. More than half have suffered from schizophrenia or some other form of mental illness. A group of Scottish researchers reported in 1990 that the affected people all carried the same genetic anomaly--a translocation, or swap, of two stretches of DNA on the long arms of chromosomes 1 and 11. With modesty, the investigators wrote that this "may be a promising area to examine" for genes that predispose people to mental illness.

The area turned out to be very promising indeed. By the year 2000, it had led researchers to a gene called DISC1, which may be a key player in the chain of events leading to mental illness. The circumstantial evidence for assigning a major role to DISC1 (Disrupted-in-Schizophrenia 1) is strong. Several studies have linked the gene to schizophrenia, major depression, bipolar disorder, and autism; recent findings on DISC1's biological function appear to support the hypothesis.
Animal studies have shown that the gene is needed for normal brain development both in the embryo and later in life and that blocking its function produces subtle abnormalities in brain structure resembling those seen in patients with schizophrenia. The protein encoded by the gene also turns out to be part of a nerve cell signaling pathway involved in learning, memory, and mood. "I think this gene is really the first big breakthrough in schizophrenia … and other mental diseases," says Christopher Ross of Johns Hopkins University School of Medicine in Baltimore, Maryland.

After decades of following false leads, researchers are cautiously optimistic that they are on the right track with DISC1. But the evidence isn't airtight. Except in the Scottish family, researchers haven't consistently linked any particular DISC1 variant to a mental disease. "There's no smoking gun," cautions psychiatrist Daniel Weinberger of the National Institute of Mental Health in Bethesda, Maryland. But if the connection of DISC1 to mental disorders holds up, it might lead to better therapies for treating the conditions--especially schizophrenia, a devastating disease that is now poorly controlled at best.