Linkage Studies Show Promise of Finding Genes that Cause Depression, U Medical School Researchers Say

Linkage Studies Show Promise of Finding Genes that Cause Depression, U Medical School Researchers Say

Feb 10, 2005 5:00 PM

Major depressive disorder (MDD) may affect up to 17 percent of the U.S. population--with an annual cost of $43 billion--but its underlying causes remain a medical mystery.

In recent years, however, researchers have made strides using linkage analysis to search for genes that predispose people to depression and by studying specific aspects of major depressive disorder, such as early onset and recurrent MDD and the higher incidence among women.

University of Utah School of Medicine researchers, in an article published online in the journal Trends in Molecular Medicine, say linkage analysis has identified specific chromosomes and that future research should focus on these chromosomes to look for genes that predispose people to MDD, the leading cause of disability among people age 15-44. Researchers also should pay close attention to other disorders that occur with MDD and why two to three times more women than men grapple with the problem.

"Contrary to what has previously been assumed for very common disorders, such as MDD, it seems that we may be able to make some headway using linkage analysis to find genes to study major depressive disorder," said Nicola J. Camp, Ph.D., associate professor of medical informatics and the studys lead author. "Identifying the genes involved might be the best way to understand the disease."

Linkage analysis is a technique that uses families to identify the chromosomes that harbor genes involved in a disease. When predisposition genes are passed from parent to offspring, the genetic markers near the genes tend to stay with the gene and are passed from one generation to the next. By studying families in which MDD is passed, researchers can pinpoint which genetic markers are shared and can conclude that genes responsible for the disease are on the chromosome near the markers.

In analyzing seven recent genomewide linkage studies, including one of her own, that looked at families in which MDD occurred, Camp identified six chromosomes among the studies that would be good places to look for MDD predisposition genes. These chromosomes are: 2q; 3centr; 8p; 12q; 15q; and 18q.

"The level of overlap in these studies is pleasantly surprising and bodes well for future positional cloning projects to identify predisposition genes," she said. "The genes identified might lead to better clinical characterization of MDD and improved management of the disease through targeted treatment and therapies."

Four of the seven studies focused on recurrent MDD in the participating families, while three of the studies concentrated on early onset MDD among participants. These characteristics may indicate that MDD is more likely genetic in nature, rather than environmental. Six of the seven studies imply that other illnesses, such as bipolar disorder and neuroticism, also may be caused by the same genes as MDD.

These findings show that it might be useful to look closely at early onset and recurrent MDD and also to consider the occurrence of MDD in association with other mental issues, according to Camp. "This may give us a better idea of the shared genetic etiology among psychiatric disorders."

MDD is characterized by two or more weeks of depressed mood and/or reduced capacity for pleasure. Sleep and appetite disturbance, impaired concentration, reduced energy, and feelings of guilt or worthlessness are symptoms that can accompany MDD.

Lisa A. Cannon-Albright, Ph.D., professor of medical informatics, co-authored the study.

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