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Study Suggests Novel Target for New Antidepressants

April 13, 2020

The protein GPR56 may provide an easy-to-measure biomarker of a patient’s response to antidepressants as well as a novel drug target for the treatment of major depressive disorder, according to a study published in Nature Communications.

“Overall, our results suggest that GPR56 is a potential target for development of antidepressant drugs,” wrote an international consortium of researchers and clinicians led by professor Gustavo Turecki, MD, PhD, of McGill University in Montreal, Quebec, Canada. 

Researchers looked at changes in gene activity in the blood of 424 patients treated with serotonin-norepinephrine reuptake inhibitors. Patients who responded to antidepressant treatment showed a significant increase in the protein GPR56, the study found, while patients who did not respond and patients who received placebo did not demonstrate an increase in the protein. GPR56 can be measured with a simple blood test, researchers noted. 

Machine Learning Uses EEG Data to Predict Antidepressant Response

Experiments with mice as well as investigation using human brain tissue from the Douglas Bell-Canada Brain Bank confirmed GPR56 was associated with biological changes in the central nervous system. GPR56 was changed in depression, they found, and was modified in both the blood and brain upon administration of antidepressants. Changes were especially evident in the prefrontal cortex, researchers reported, a brain region important for emotional regulation and cognition.

The findings provide a greater understanding of the pathophysiology of depression, researchers wrote, and suggest a new drug target for antidepressants.

“Identifying new therapeutic strategies is a major challenge, and GPR56 is an excellent target for the development of new treatments of depression,” Dr. Turecki said. “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.”

—Jolynn Tumolo

References

Belzeaux R, Gorgievski V, Fiori LM, et al. GPR56/ADGRG1 is associated with response to antidepressant treatment. Nature Communications. 2020;11(1):1635. 

Promising advance in depression research [press release]. Montreal, Canada: McGill University; April 8, 2020. 

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