Researchers at Yale University discovered why depression and chronic stress can cause the brain to shrink, which in turn contributes to cognitive and emotional impairments.
The team found that brain shrinkage is due to a single genetic switch which triggers a loss of brain connections in humans and depression in animals. Known as a transcription factor, this genetic switch represses the expression of several genes that are required for the formation of synaptic connections between brain cells, which can cause the prefrontal cortex to lose brain mass.
"We wanted to test the idea that stress causes a loss of brain synapses in humans," said senior author Ronald Duman, PhD, Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology and of pharmacology at Yale School of Medicine. "We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated."
Brain tissue of depressed and non-depressed patients donated by the brain bank was analyzed by researchers, who were looking for unique patterns of gene activation. They found that patients who were not depressed had lower expression levels in genes required for the function and structure of brain synapses.
H.J Kang, postdoctoral researcher and lead author of the study, discovered through mouse studies that a transcription factor called GATA1 could help regulate at least five of these genes. When activated, the transcription factor caused rodents to show depressive symptoms. This suggests that GATA1 could be responsible for both the loss of connection between neurons and the symptoms of depression.
GATA1 could possibly help identify those who are sensitive to stress or at high risk of major depression.
"We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies," Duman said.
The study was funded by the National Institutes of Health and the Connecticut Department of Mental Health and Addiction Services. Findings were reported in the journal Nature Medicine in August 2012.
Source: e! Science News