A team of experts at McGill University has identified a protein that plays a central role in the biological changes associated with depression. The discovery may ultimately lead to the development of more effective antidepressants and improved treatments for depression, which is a leading cause of disability worldwide.
Depression is a mood disorder that affects more than 264 million people of all ages. Antidepressants are the most common form of treatment for depression. While these medications can be very effective, only 40 percent of patients respond to the first type of antidepressant they are prescribed.
The McGill research team, led by Professor Gustavo Turecki, has pinpointed the protein GPR56 as a target for new and improved antidepressants.
The experts analyzed changes across gene activity in blood samples from over 400 patients who were being treated with antidepressants.
The study revealed significant changes in the levels of GPR56 in patients who responded favorably to antidepressants. The changes were not found in patients who had no response to the treatment or in those who received a placebo. The findings suggest that an individual’s response to antidepressants can be measured with simple blood tests.
Using human brain tissue and experiments with mice, the researchers confirmed that GPR56 was linked to biological changes in the central nervous system. The team found that depression was associated with distinctive changes in GPR56. When antidepressants were administered, GPR56 was modified in both the brain and the blood.
Significantly, the GPR56 changes were most evident in the prefrontal cortex. This part of the brain is not only involved in emotional responses, but also has connections with brain regions that control critical substances for mood regulation: dopamine, norepinephrine, and serotonin.
“Identifying new therapeutic strategies is a major challenge, and GPR56 is an excellent target for the development of new treatments of depression,” said Professor Turecki. “We are hopeful that this will provide an avenue to alleviate the suffering of patients who face this important, and often chronic, mental illness which is also strongly associated with the risk of addiction and an increased risk of suicide.”
The study is published in the journal Nature Communication.