Identification of the glutamate transporter gene SLC1A1in different studies on familial obsessive compulsive disorder advances understanding of the disorder and may lead in the short term to screening tests for close relatives of patients, according to two articles in the July issue of the Archives of General Psychiatry.

It has long been established that obsessive compulsive disorder tends to run in families; close relatives of patients with the disorder are up to nine times more likely to develop it themselves.

Now, research is shedding new light on one of the genetic factors that may contribute to that pattern. Although no one gene causes the disorder, research from North America is helping scientists confirm the importance of a particular gene that has previously been suspected to play a major role in development of the disorder.

The glutamate transporter gene called SLC1A1 encodes a protein called EAAC1 that regulates flow of glutamate in and out of brain cells. Thus variations in the gene might lead to alterations in that flow, possibly contributing to increased risk for the disorder.

The new findings are especially important not only because of the simultaneous discoveries reported in the papers, but also because previous studies had shown a functional link between glutamate and the disorder. Brain imaging and spinal fluid studies have shown differences in the glutamate system between patients and healthy volunteers, including areas of the brain where the EAAC1 protein is most common.

“Taken together, these findings suggest that SLC1A1 is a strong candidate gene for obsessive compulsive disorder, which if confirmed, could lead to improvements in understanding and treating this condition, and screening those with an elevated risk,” said Gregory Hanna, MD, senior author on one of the papers. “It’s possible that altered glutamate activity in some brain regions may contribute to the obsessions and compulsions that are the hallmark of obsessive compulsive disorder.”

While the new findings are exciting because they strengthen the evidence for glutamate’s role in vulnerability to the disorder, the researchers caution that more work needs to be done before their discovery has any impact on treatment.

Four years ago, a team published a genome scan from young patients and their parents that found signs of disorder-related genetic variations on chromosome 9, in the area of SLC1A1.

Since that time, they have been zeroing in on the gene and its nearby stretches of DNA, using analyses of single nucleotide polymorphisms that look at specific differences between individuals within the gene. At the same time, the Canadian group has been focusing on that same area in studies involving adult and child patients and their close relatives.

The first new paper is based on genetic samples from 71 patients (children and adults) and their parents. It finds a significant association between early-onset obsessive compulsive disorder and genetic variations at several sites on the SLC1A1 gene. A strong association at two of those sites was only seen in male early-onset patients, which surprised the researchers but may make sense in that early-onset disease is more common in boys. As many as half of all patients with the disorder experience their first symptoms in childhood or adolescence.

The second new paper is based on data from 157 patients and 319 first-degree relatives. It finds linkages between the disorder and three locations on the SLC1A1 gene.

In a commentary published in the same issue, two Yale University researchers call the new findings promising and call for additional research. “These data add to a growing body of work that suggests that SLC1A1 is perhaps a primary candidate gene for OCD,” they wrote.

Hanna noted that the finding of genetic vulnerabilities for the disorder are important, but so is the understanding of how environmental factors ? including hormones and infections ? may play a role in the onset of clinical disease.

As research continues, Hanna and colleagues hope to eventually conduct clinical trials of glutamate-targeting medications in patients and to collect more DNA and blood samples from patients and families. They are also looking at other regions of the genome that might contain gene variations that are more common in people with the disorder.