Science Update April 07, 2008
OCD Risk Higher When Several Variations in Gene Occur Together
Several variations within the same gene act together to raise the risk of obsessive-compulsive disorder (OCD), new NIMH research suggests. The gene produces a protein that helps make the brain chemical serotonin available to brain cells.
OCD, an anxiety disorder, affects an estimated 2.2 million Americans age 18 or older. Symptoms usually begin sometime between childhood and early adulthood. The rituals and intrusive, unshakeable thoughts of OCD sometimes become severely disabling.
Some people respond well to treatment, but others don’t. Findings from the new study can help scientists understand the biological aspects of what goes wrong in the brain in OCD and identify molecular targets for new medications. With further research, the findings also could help doctors identify patients at risk.
Previously, the gene variations had been implicated in OCD individually, in separate studies – but other studies sometimes found that the variations had no impact on risk of OCD. The reason for the inconsistent results appears to be that the variations have an impact on OCD risk when they occur together, not individually, NIMH researchers Jens R. Wendland, Pablo R. Moya, Dennis L. Murphy, and colleagues reported in the March 1 issue of Human Molecular Genetics.
The gene in which the variations occur is called SLC6A4, and the protein it makes is called the serotonin transporter. Researchers looked at the gene in 295 people with OCD and 657 people without OCD, for comparison. They found that 9.3 percent of the people with OCD had the combination of variants in the gene, compared with only 5.9 percent of the people who didn’t have OCD. The likelihood that the difference was a chance finding is low.
One reason the scientists focused on the serotonin-transporter gene for clues about OCD was that medications called selective serotonin reuptake inhibitors (SSRIs), which are taken by depressed patients to boost serotonin levels in the areas between brain cells, also help some people with OCD. This suggests that flaws in the serotonin system are part of the pathology that leads to the disorder.
The new findings suggest not only that the serotonin transporter is involved in OCD, but also that part of the problem may be excess activity of the gene that makes the transporter. Excessive activity of this gene results in too much serotonin being shuttled out of the areas between brain cells, making less of it available for important cell functions.
Wendland JR, Moya PR, Kruse MR, Ren-Patterson RF, Jensen CL, Timpano KR, Murphy DL. A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive-compulsive disorder. Hum Mol Genet. 2008 Mar 1;17(5):717-23. Epub 2007 Nov 30. PubMed PMID: 18055562.
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