Discovery of How Antidepressants Work Leads Toward Improved Depression Treatments

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Hongjun Song, Ph.D., Johns Hopkins University School of Medicine, Expert on Depression
Hongjun Song, Ph.D.

Building on findings from stem cell research in 2011 that helped explain how the brain can regenerate, NARSAD Grantees performed a sophisticated series of experiments and analyses that led them to discover a protein that helps electroconvulsive therapy (ECT) and antidepressant medications work. It was known that these therapies work by stimulating stem cell development in the brain, but it was not known how. The protein identified is produced by an inhibitor gene (sFRP3), known to regulate neural stem cells and the creation of new neurons. It appears that both antidepressant medication and ECT reduce the amount of protein produced by the sFRP3 gene, which then stimulates neural stem cell activity and the growth of new neurons.

The results of this new work may enable future diagnostic tests to predict an individual’s likely response to antidepressant treatment based on their genetic code as well as provide a new target for the development of next generation therapies. The findings were published online in Molecular Psychiatry on Dec. 4, 2012 and in Cell Stem Cell on Feb. 7, 2013.

"Previous studies have shown that antidepressants and electroconvulsive therapy both activate neural stem cells in the adult brain to divide and form new neurons," says NARSAD Grantee Hongjun Song, Ph.D., Professor, Neurology & Neuroscience and Director, Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University Medicine School of Medicine. "What were missing were the specific molecules linking antidepressant treatment and stem cell activation."

Other NARSAD Grantees involved in these studies include Mi-Hyeon Jang, Ph.D., Kimberly M. Christian, Ph.D., Guo-li Ming, M.D., Ph.D. and Mikhail V. Pletnikov, M.D., Ph.D. of the Johns Hopkins University; René Hen, Ph.D., Columbia University; and Elisabeth B. Binder, M.D., Ph.D., Max Planck Institute of Psychiatry.

Read the news release

Read more in the Molecular Psychiatry paper

Read about Dr. Song and his team’s discovery in 2011 – one of the Foundation’s 10 Research Highlights of 2011

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Please note that researchers cannot give specific recommendations or advice about treatment; diagnosis and treatment are complex and highly individualized processes that require comprehensive face-to- face assessment. Please visit our "Ask an Expert" section to see a list of Q & A with NARSAD Grantees.
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