December 10, 2013
Scientists Discover Gene That May Predict Response To Antidepressants
redOrbit Staff & Wire Reports - Your Universe Online
Treating depression using selective serotonin reuptake inhibitors (SSRIs) is often a trial-and-error process, but new research appearing in the journal Translational Psychiatry lays the foundation for a new genetic test that could allow doctors to provide patients with a personalized treatment program.
Researchers at Tel Aviv University (TAU) explained that SSRIs do not work for everyone, even though they are the most commonly prescribed form of antidepressants. Patients are often asked to start using one type of SSRI, with its own unique set of side effects, for three to four weeks to see if it is effective.
However, the study authors report that they have discovered a gene which could indicate whether or not one type of SSRI medication will be effective for a certain patient. Provided this biomarker is validated through clinical trials, it could be used to create a genetic test that could lead to an individualized treatment approach, they said.
“SSRIs only work for about 60 percent of people with depression,” Dr. David Gurwitz of the Department of Molecular Genetics and Biochemistry at TAU's Sackler Faculty of Medicine, said in a statement Monday. “A drug from other families of antidepressants could be effective for some of the others. We are working to move the treatment of depression from a trial-and-error approach to a best-fit, personalized regimen.”
According to the university, over 20 million Americans annually are diagnosed with debilitating depression which requires clinical intervention. SSRIs (which include medications such as Zoloft and Prozac) are among the newest and most popular forms of treatment for the condition, and are believed to work by blocking the reabsorption of the neurotransmitter serotonin in the brain and helping to boost a person’s overall mood.
In order to locate the genes potentially responsible for the brain’s responsiveness to these drugs, Dr. Gurwitz and his colleagues applied the SSRI Paxil to 80 cell lines from the National Laboratory for the Genetics of Israeli Populations (NLGIP), a genetic data biobank located at the Sackler Faculty of Medicine.
“The TAU researchers then analyzed and compared the RNA profiles of the most and least responsive cell lines,” the university said. “A gene called CHL1 was produced at lower levels in the most responsive cell lines and at higher levels in the least responsive cell lines. Using a simple genetic test, doctors could one day use CHL1 as a biomarker to determine whether or not to prescribe SSRIs.”
“We want to end up with a blood test that will allow us to tell a patient which drug is best for him. We are at the early stages, working on the cellular level. Next comes testing on animals and people,” added TAU doctoral student Keren Oved, who led the research along with fellow student Ayelet Morag.
They also set out to determine why CHL1 levels could predict whether or not a person would respond to SSRIs, so they applied Paxil to human cell lines for three weeks – the time required to achieve a clinical response. They discovered that the drug increased production of ITGB3, a gene which is believed to interact with CHL1 in order to encourage the development of new neurons and synapses, according to the researchers.
“The result is the repair of dysfunctional signaling in brain regions controlling mood, which may explain the action of SSRI antidepressants,” the university said. “This explanation differs from the conventional theory that SSRIs directly relieve depression by inhibiting the reabsorption of the neurotransmitter serotonin in the brain… The TAU researchers are working to confirm their findings on the molecular level and with animal models.”