A possible genetic explanation for a rare form of Obsessive-Compulsive Disorder, or OCD, has been found by Yale researchers and the National Institutes of Mental Health, or NIMH.

A specific genetic mutation was found in some patients with OCD in the gene coding for human serotonin transporter, or hSERT. Serotonin is a neurotransmitter in the human body, which is released from one nerve cell and binds to receptors on the surface of the next cell to transmit a signal. hSERT transports this serotonin back into the cell that released it. Some antidepressants function by inhibiting this uptake.

The genetic variation has two parts. The first mutation is in hSERT, and the second is in the promoter region of the gene, which determines how much of a protein is produced.

While other studies have explored the connection between psychiatric disorders and protein mutations, these findings show the strongest correlation.

“It’s the best example of a known protein that’s important in the nervous system [having] a specific defect that causes or is associated with — psychiatric disorders,” said Dr. Gary Rudnick, professor of pharmacology at Yale School of Medicine, who conducted the research at Yale.

Dr. Dennis Murphy at NIMH, along with other scientists, first detected the gene mutation in two unrelated families with members who have OCD. Rudnick and Dr. Fusun Kilic, also of Yale, studied the effects of the mutation in cells in a laboratory.

Rudnick said the findings were especially interesting because, unlike most mutations, this mutation actually causes increased transporter activity.

“We [took] the same mutation and [made] it in the transporters that were expressed in cells in the laboratory to study the function of the serotonin transporter,” he said. “We found that the mutant transporter had more activity than the [normal] transporter. If you think about all the time nature had to perfect the transporter, you wouldn’t think a rare mutation would make it work better than it was evolved to work. As it turns out, the mutation seems to prevent the proper regulation of hSERT, so it always functions at top speed and can’t be slowed down.”

However, the findings do not support a single genetic basis for the disease. Dr. Ben Greenberg, director of the OCD Clinic at Butler Hospital at Brown University and co-author of the study that originally found the mutation in patients, said the mutation is not the cause of OCD but rather is useful in understanding how genetic mutations cause or affect disorders.

“In two families, [the study results] looked like a particular variant of a gene was associated with OCD,” Greenberg said. “That doesn’t really say how genetic OCD is in general, and it doesn’t talk about the genetic incidences for most cases of OCD, because this was an uncommon gene variant. What it does is it gives you a bit of a model of how the genetics of OCD and other complex illnesses — might work.”

The findings will lead to more research to determine the effect of the gene mutation and its specific relation to OCD.

“I think that it’s a long road ahead in terms of getting to [treatment],” Rudnick said. “But one of the things we’d like to do is to discover how the activity of serotonin transport leads to all of the symptoms, [including OCD], seen in these people. It may affect the development of the brain in early stages, telling cells how to grow and where to grow. But there are a lot of questions.”

Greenberg’s clinic will continue to study patients with OCD and encourage anyone who has the disease or is interested in getting more information to contact the Butler Hospital at Brown University.

Patricia Perkins, executive director of the Obsessive-Compulsive Foundation Inc., stressed that such studies are only in their first stages.

“The research was actually completed two years ago; it just took that long for it to come out in Molecular Psychiatry,” Perkins said. “So it’s not the beginning of the end; it’s the beginning of the beginning.”