Depression and chronic stress have been known to cause a loss in brain volume which leads to serious impairment of an individual's emotional well being and cognition. Now scientists at Yale University have determined one of the reasons as to why this occurs. Researchers have discovered a single genetic switch that triggers the loss of brain connections in humans and depression in animal models.
As part of the effort, the team analyzed brain tissue from depressed and non-depressed subjects from a brain bank to study different patterns of gene activation. It was found that brains of depressed patients expressed genes required for function and structure of brain synapses, the specialized junctions where neural cells (neurons) communicate with target cells, at lower levels. This repression of gene expression necessary for the formation of synaptic connections between brain cells could in turn contribute to the loss of brain mass in the prefrontal cortex.
The scientists also discovered that at least five of these genes were regulated by a single transcription factor or a genetic switch called GATA1. When the transcription factor was activated in rodents, the animals exhibited depression-like symptoms. This led them to conclude that GATA1 not only played a role in loss of connections between neurons but also caused symptoms of depression.
Ronald Duman, Professor of Psychiatry and professor of neurobiology and of pharmacology at the Yale School of Medicine and senior author of the study said, "We wanted to test the idea that stress causes a loss of brain synapses in humans."
He added "We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated."
The researcher believes that genetic variations in GATA1 may help identify people at a greater risk of falling into major depression or sensitivity to stress.
He added "We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies."
The findings were published in the August 12 issue of the journal Nature Medicine.
by RTT Staff Writer
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