By Rachel Dinh & NoCamels Team July 01, 2014
Doubts about the effectiveness of antidepressants have been raised since they were invented, but now new research pinpoints why existing treatments don’t entirely work as they should.
According to the World Health Organization, mood disorders such as depression afflict about 10 percent of the global population. With so many people affected, the scientific community has invested much time and effort in understanding these diseases. Yet the molecular and cellular mechanisms that underlie these destructive ailments are still not fully understood.
While there are medications available to patients experiencing mood disorders, the existing anti-depressants are hardly sufficient: Some 60-70 percent of patients experience no relief from them. For the other 30-40 percent, that relief is often incomplete, and usually only comes after patients take the drugs for a prolonged period of time. In addition, there are many psychological and physical side effects associated with these drugs. New and more effective medications are clearly needed — an undertaking that requires, first and foremost, a better understanding of the processes and causes underlying the disorders.
Serotonin, colloquially known as the “happy chemical,” is a neurotransmitter that helps relay messages from one area of the brain to another. Many researchers believe that an imbalance in serotonin levels may be responsible for causing depression and other mood disorders.
In order to examine the veracity of this assertion, Weizmann Institute Prof. Alon Chen and Dr. Orna Issler researched the role of tiny molecules called microRNA molecules (molecules that regulate cellular activity) in the nerve cells that produce serotonin and made some surprising findings. They succeeded in identifying, for the first time, the unique “fingerprints” of a microRNA molecule that acts on the serotonin-producing cells. Through further experimentation, Chen and his team were able to find a connection between this particular microRNA (miR135) and two proteins that play a key role in serotonin production and the regulation of its activities. The findings recently appeared in “Neuron.”
The scientists noted that in the area of the brain containing the serotonin-producing nerve cells, miR135 levels increased when antidepressant compounds were introduced. Mice that were genetically engineered to produce higher-than-average amounts of the microRNA were more resistant to constant stress: They did not develop any of the behaviors normally associated with chronic stress, such as anxiety or depression. In contrast, mice that expressed low levels of miR135 exhibited more of these behaviors; in addition, their response to antidepressants was weaker.
Harnessing the influence of miR135 on depression
The conclusion of the findings is that the brain needs the proper miR135 levels – low enough to enable a healthy stress response and high enough to respond to serotonin-boosting medications to avoid depression and anxiety disorders. When this idea was further tested, the researchers found that people who suffered from depression had unusually low miR135 levels in their blood. Upon closer inspection, the scientists discovered that the three genes involved in producing miR135 are located in areas of the genome that are known to be associated with risk factors for bipolar mood disorders.
This discovery is especially promising for the future of mood disorder detection and treatment. Blood tests for mental illnesses were previously regarded as impossible. But following this discovery, blood tests for conditions like depression and bipolar disorder may be made available in the not-so-distant future.The researchers hope that the miR135 molecule can be used to serve as an indicator of the disease through simple blood tests. In addition, the molecule could serve as a target whose levels might be raised in patients suffering from these disorders. Yeda Research and Development Co. Ltd., the technology branch of the Weizmann Institute, has applied for a patent connected to this research and licensed the rights to miCure Therapeutics to develop a new diagnostic method and medication based on these findings.