People who suffer from chronic stress or major depression tend to lose brain volume, and such loss can lead to both emotional and cognitive dysfunction. Now new research led by Yale scientists reveals how this loss of volume occurs.
The findings point to a single genetic switch that triggers a decline in brain connections in humans and leads to depression in animal models.
This genetic switch, known as a transcription factor, inhibits the expression of several genes that are needed to form synaptic connections between brain cells, which in turn could lead to a loss of brain mass in the prefrontal cortex.
“We wanted to test the idea that stress causes a loss of brain synapses in humans. We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated,” said senior author Ronald Duman, Ph.D.
For the study, the researchers looked for different patterns of gene activation in the brain tissue of depressed and non-depressed patients donated from a brain bank.
The brain tissue of depressed patients had a lower level of expression in genes necessary for the function and structure of brain synapses.
Lead author and postdoctoral researcher H.J. Kang, Ph.D., found that at least five of these genes could be regulated by a single transcription factor called GATA1. In an animal study, when this factor was activated, rodents exhibited depressive-like symptoms, suggesting GATA1 plays a role not only in the loss of connections between neurons but in symptoms of depression as well..
Duman theorizes that, sometime in the future, genetic variations in GATA1 may help identify individuals 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,” said Duman.
The findings are published in the journal Nature Medicine.
Source: Nature Medicine