Stress and Depression Can Shrink the Brain

A team of researchers led by Yale scientists has discovered that major depression or chronic stress can cause the loss of brain volume, a condition that contributes to both emotional and cognitive impairment.

The finding published in the August 12 issue of the journal Nature Medicine, clearly depict  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."

In order to conduct the study the researchers analyzed tissue of depressed and non-depressed patients donated from a brain bank and looked for different patterns of gene activation.

They noticed that the brains of the 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 concluded saying, "We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies."