Foundation Grantee and Team Discover New Target for Depression Treatment

NARSAD Grantee Scott Russo, Ph.D., Assistant Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai in New York and Expert on Depression
Scott Russo, Ph.D.

NARSAD Grantee Scott Russo, Ph.D., Assistant Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai in New York, and a team of researchers recently discovered that decreased expression of the protein called “Rac1” may be a primary cause of depression. They also found that overexpression of the same protein reversed depression-related behaviors in mice, indicating that Rac1 is a promising target for new medication treatments. The results of their study were published Feb. 17, 2013 in Nature Medicine.

The researchers found lower Rac1 in mouse brains after experiencing chronic stress and also in postmortem brains of humans with major depressive disorder. By manipulating the expression of Rac1, they were able to control the depressive response in mice.

“Knocking out,” or diminishing the expression of, Rac1 caused social defeat in mice whereas stimulating an over-expression of Rac1 normalized the mice after social defeat. This indicates that stimulating expression of Rac1 through an infusion may improve neuroplasticity in the brain.

“Our study is among only a few in depression research in which two independent human cohorts and animal models validate each other,” said Dr. Russo. “Rac1 has enormous therapeutic potential, and I look forward to investigating it further.” Dr. Russo hopes to gain a better understanding of the role of Rac1 on the brain and to explore the possibility of biomarkers identified in blood tests to indicate dysfunction. After further investigation, he hopes to explore pharmacologic compounds that manipulate Rac1.

Read the study article