H J Kang Finds Switch that Shrinks Depressed Brains

Yale postdoctoral researcher Hyo Jung Kang has discovered the bio-chemical switch that, in depressed people, turns off at least five genes involved in creating brain synapses. Her discovery will advance efforts to find effective treatments for depression.

Kang’s team analyzed tissue of depressed and non-depressed patients donated from a brain bank for differences in patterns of gene activation. The brains of patients who had been depressed showed lower levels of expression in genes required for the function and structure of brain synapses.

In an effort to seek out the mechanism that switched off the expression of the affected genes, Kang’s team injected the brains of test rodents with transcription factor GATA-1. The rodents came to show symptoms like those shown by depressed individuals, suggesting that GATA-1 can cause both loss of connections between neurons and the symptoms of depression.

This study helps explain why depression and chronic stress has been shown to cause the loss of brain volume in the prefrontal cortex which in turn contributes to both emotional and cognitive impairment. Expression of a single gene dramatically decreases synaptic connections between brain cells.

“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.”

Genetic variations in GATA-1 may be used to identify people at high risk for major depression or sensitivity to stress. More importantly, the study may lead to the discovery of therapies that can help depressed patients by enhancing synaptic connections.

The study was reported in the August 12 issue of the jurnal Nature Medicine. It was funded by the National Institutes of Health and the Connecticut Department of Mental Health and Addiction Services. The study’s other authors are Bhavya Voleti, Pawel Licznerski, Ashley Lepack, and Mounira Banasr.

Hyo Jung Kang received her BS in biological sciences and masters in neuroscience, respectively, in 1995 and 1997 from Ewha Woman’s University in Seoul. She received a PhD in neuropharmacology from the Ajou University School of Medicine in Suwon, Korea in 2003. Her dissertation subject was an investigation of the neuronal death mechanism.

She joined Yale University School of Medicine’s Department of Psychiatry in 2004 where she conducted gene profiling studies in postmortem brains of patients with major depressive disorders. In 2009 she was promoted to associate research scientist at Yale Med School’s department of neurobiology.