Study links stress, brain shrinkage

A team of Yale researchers have discovered a cognitive mechanism that can cause stress to shrink the human brain.
A team of Yale researchers have discovered a cognitive mechanism that can cause stress to shrink the human brain. Photo by Robert Peck.

As if you needed yet another reason to get through shopping period as quickly as you can, a team of Yale researchers have discovered a cognitive mechanism that can cause stress to shrink the human brain.

The study, led by postdoctoral researcher Hyo Jung Kang, found that a type of genetic switch called a “transcription factor” can repress the expression of certain genes necessary for connections between brain cells, or synapses, to form properly. Without these connections, a loss of brain mass in the prefrontal cortex can occur, since cells cannot properly grow without the expression of the gene. The study found that the transcription factor in question, GATA1, is activated in conjunction with stress and feelings of depression.

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

Duman said that researchers based this new study on previous research that had been conducted on rodent models. He said these tests showed chronic stress could cause atrophy of neurons in brain regions that control emotion, mood and cognition, and that this helped the team to identify the genes that were altered in a depressed subject’s brain. To isolate the genes involved in synaptic connections, the researchers examined the entire genome to find the genes whose expression was affected by the transcription factor in question.

Once the brain regions in question were identified, Duman said, the team collected samples for analysis. In this case, samples of brain tissue from deceased depression and chronic stress sufferers were examined.

Duman said the study’s findings demonstrate atrophy of synaptic connections in human depression for the first time, consistent with the rodent studies. The results also show that GATA1 underlies the effects of depression and stress on synaptic atrophy, he said.

“[The study’s results] identify specific synapse related genes that are altered in depression,” Duman said.

Duman added that linking neural atrophy to depression could mean treatments that reverse the atrophy of neurons or that increase synaptic connections may be useful antidepressant measures.

University of Michigan associate psychiatry professor Bruno Giordani said the study could be useful for scientists trying to understand not just stress, but other conditions as well. He said that previous research in the field shows connections between stress and afflictions such as Alzheimer’s disease and dementia, and that this new study could prove useful in identifying those at greater risk for such issues later in life.

Matthew Friedman, a professor of psychiatry at Dartmouth and the executive director of the National Center for Posttraumatic Stress Disorder, said further study of GATA1 could help to treat PTSD as well.

“This is an extremely important finding,” Friedman said. “Identifying how a single transcription factor, induced by depression or stress, can disrupt synaptic connections will focus future research on mechanisms that reverse this process.”

The study was published in the scientific journal Nature Medicine on Aug. 12.

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