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August 15, 2012 (TSR) – Major depression or chronic stress can cause the loss of brain volume, a condition that contributes to both emotional and cognitive impairment. Now a team of researchers led by Yale scientists has discovered one reason why this occurs — a single genetic switch that triggers loss of brain connections in humans and depression in animal models.

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The findings, reported in the Aug. 12 issue of the journal Nature Medicine, show that the genetic switch known as a transcription factor represses the expression of several genes that are necessary for the formation of synaptic connections between brain cells, which in turn could contribute to loss of brain mass in the prefrontal cortex.

“We wanted to test the idea that stress causes a loss of brain synapses in humans,” said senior author Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology and of pharmacology. “We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.”

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The research team analyzed tissue of depressed and non-depressed patients donated from a brain bank and looked for different patterns of gene activation. The brains of patients who had been depressed exhibited lower levels of expression in genes that are required for the function and structure of brain synapses. Lead author and postdoctoral researcher H.J. Kang discovered that at least five of these genes could be regulated by a single transcription factor called GATA1. When the transcription factor was activated, rodents exhibited depressive-like symptoms, suggesting GATA1 plays a role not only in the loss of connections between neurons but also in symptoms of depression.

Duman theorizes that genetic variations in GATA1 may one day help identify people at high risk for major depression or sensitivity to stress.

“We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies,” Duman said.


Hyo Jung Kang, Bhavya Voleti, Tibor Hajszan, Grazyna Rajkowska, Craig A Stockmeier, Pawel Licznerski, Ashley Lepack, Mahesh S Majik, Lak Shin Jeong, Mounira Banasr, Hyeon Son, Ronald S Duman, Decreased expression of synapse-related genes and loss of synapses in major depressive disorder, Nature Medicine, 2012; DOI: 10.1038/nm.2886


  1. I seem to be missing something. You dropped the Yale name once at the beginning of this “report”. I see no peer-reviewed studies, that support your hypothesis although we know that depression comes to us through nature, nurture and choice of response to various stimulus in our environment. are your conclusions based on the same type of investigation that told us that alcohol consumption kills brain cells? Since I almost never experienced depression, does that mean my brain is expanding at a dangerous rate. You might want to proceed more scientifically along this line of thought before you blurt out conclusions that cannot be substantiated. Opinion is not fact, information is not knowledge. Dance on.


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