Depression affects the well-being of a significant number of adults in the United States. Although medication is available for treating clinical depression, some of these drugs take a long time to work or may pose health risks because of their side effects. However, a new mouse study paves the way for a more effective treatment of depression in humans.
The Centers for Disease Control and Prevention (CDC) report that 8 million U.S. individuals were diagnosed with major depressive disorder between 2009 and 2010, and that the condition accounted for almost 43,000 deaths during that time.
Treatment options available for people with depression include psychotherapy and medication. Antidepressants work for most people, however for others, the side effects pose serious health risks. The medication may lead to suicidal thoughts or even suicide attempts in some people, especially during the initial period of 2 to 4 weeks before the drugs start to work.
In an attempt to come up with a better alternative to the antidepressants currently on the market, researchers from the University of California (UC) San Diego School of Medicine have set out to study depression in mice. The team – led by Abraham Palmer, Ph.D., professor of psychiatry and vice chair for basic research at the UC San Diego School of Medicine – found that inhibiting a certain enzyme alleviates symptoms of depression in mice.
The findings were published in the journal Molecular Psychiatry.
Palmer and team inhibited an enzyme called Glyoxalase 1 (GLO1). GLO1 has been shown to inhibit, in its turn, a byproduct that results from the cell’s metabolism. This byproduct inhibits neurons and influences mood and behavior.
The team divided the mice into three groups: those that received the new treatment, those that received the traditional Prozac medication, and those that were left untreated.
Palmer and colleagues then administered various well-established depression tests to examine the impact of GLO1 inhibition. These included the forced swim test – a behavioral test commonly used to assess the degree of “hopelessness” or “despair” in rodents – as well as the chronic mild stress paradigm and the removal of the mice’s olfactory bulb in order to test how quickly the antidepressants work.
All of these tests revealed that inhibiting the GLO1 enzyme reduced symptoms of depression in mice in as little as 5 days, whereas 14 days passed before Prozac showed any therapeutic effect.
“There are currently no approved fast-acting antidepressants, so finding something like this is unusual,” explains study co-author Stephanie Dulawa, Ph.D., associate professor of psychiatry at the UC San Diego School of Medicine.
Even though developing the equivalent of a GLO1 inhibitor in humans might take years, the findings open new avenues for more effective antidepressive medication. Palmer and team have already started to collaborate with UC San Diego chemists in an effort to develop GLO1 inhibitors for humans.
“Depression affects at least 1 in 6 of us at some point in our lifetime, and better treatments are urgently needed. A better understanding of the molecular and cellular underpinnings of depression will help us find new ways to inhibit or counteract its onset and severity.”
Abraham Palmer, Ph.D., senior author