Study Shows Genes Could Be Factor in Treatment of Depression
However, a new study proves that there is a more accurate way to match the right patient with the right drug without having to resort to a trial-and-error process. The National Institute of Mental Health released the results of a study done by scientists showing that how a patient will respond to antidepressants may well depend on which version of a specific gene they inherit.
Dr. Francis McMahon, one of the study’s authors, said that one of the goals was simply to get some answers to an oft-asked question. “For a long time, we in psychiatry have been puzzled by the fact that antidepressants help most people but not everybody,” he said. “About 2/3 of patients improve with antidepressant therapy and at least 1/3 don’t. It hasn’t been crystal clear about why it is about that certain antidepressants help some people and some drugs don’t. The goal was to just see whether some of the old questions about antidepressant response could be put to rest at the clinical level.”
The study, dubbed the STAR*D (Sequenced Treatment Alternatives for Depression) trial, showed that 47 percent of the 2,876 patients showed improvement with the antidepressant, Celexa, which is known as an SSRI, or seratonin selective reuptake inhibitor. The goal of the STAR*D trial was to effective figure out why some people respond better to antidepressants than others.
According to the study, patients who retain two copies of one version of a gene that codes for a part of the mood-regulating system in the brain instigated a more favorable response in anti-depressant therapy by 18 percent. Patients who had two copies of the more common version of the gene had a considerably less favorable response.
The researchers looked at genetic material from 1,953 patients. They searched for a significant association between how patients fared in treatment and 768 sites of variability in 68 genes -sites where letters
in the genetic code vary across individuals, said the study.
What was found showed the strongest connection between the two factors in the gene that codes for the serotonin 2A receptor, which is located on the cortex of the brain. The serotonin 2A receptor is one of the proteins to which serotonin binds itself as brain cells communicate, according to the study. Antidepressants reduce the number of the serotonin 2A receptors in the cortex of an animal in just a few weeks, which suggests that in humans, the serotonin 2A receptors are important factors in how the drugs work in the brain.
Everyone inherits two copies of the serotonin 2A receptor gene. One is adenine (A) and the other is guanine (G). Between the two, people can have combinations of AA, GG or AG. What the study showed is that white patients with AA, about 80 percent responded to an antidepressant. This is comparison to the 60 percent with GG who responded. The study concluded that those with the AA gene were 16-18 percent more likely to benefit from taking an antidepressant. It is important to note that these results applied predominantly to white patients since they are six times more likely than a black patient to have the A version of the gene. In fact, according to the study authors, black patients didn’t respond as well in the trial overall.
The findings of the study were twofold – one aspect is that the less common version of the gene is more prevalent in white patients than in black patients (with fewer blacks responding), leading the researchers to believe that the gene may be able to explain racial differences in antidepressant treatment. The other aspect of the findings showed that this is added evidence to the theory that the components, which is acts as a receptor for serotonin, has a key role in the inner workings of the antidepressant drugs.
According to Matt McGue, professor in the Department of Psychology, University of Minnesota and in the Department of Epidemiology, University of Southern Denmark, there is reason to celebrate the findings with caution. “This research could have a profound impact on both our understanding and treatment of mood disorders. One of the hopes with the Human Genome Project was that it would lead to better pharmacological interventions for human disease, either by leading to better designed drugs or by individualizing pharmacological treatments. This study clearly is in line with this goal,” he said. “However, as a rule you want to see the study replicated. Many genetic associations like that you describe fail to be replicated in subsequent studies. So, until the findings are replicated it seems most prudent to regard the findings as provisional.”
McMahon agrees that more studies are needed in line with the STAR*D trial. “We hope that this will encourage other studies. Ultimately, the open question is, assuming we can do an experiment to look at all of the genes, how much of the overall difference of antidepressant outcome will we be able to explain?,” he said. “Right now, the influence might be in those who develop new drugs to look closely at seratonin receptors and not just at seratonin transporters. I do this it is still unclear whether or not in the long run, this study will have an impact on patient care.”
The study was authored by researchers with the National Institute of Mental Health, including Francis J. McMahon, M.D., Silvia Buervenich, Ph.D., and Husseini Manji, M.D.. There were also several other collaborators from various institutions working on the study as well.
The study was posted online in early March and will be published in the May issue of “American Journal of Human Genetics.”
