Gene linked with mental illness shapes brain region, researchers find

Dwight German
Researchers led by Dr. Dwight German, professor of psychiatry, have discovered that a gene variant linked to mental illness is associated with enlargement of a brain region that handles negative emotions.

DALLAS - Nov. 7, 2006 -  A gene variant associated with mental illness goes hand-in-hand with enlargement of a brain region that handles negative emotions, researchers at UT Southwestern Medical Center and the Central Texas Veterans Health Care System have found.

The region of the brain called the pulvinar is larger and contains more nerve cells in humans who carry the gene.

"This might indicate that the brain regions that receive input from the pulvinar are more strongly influenced in such individuals, and the pulvinar communicates with brain regions involved in negative emotional issues," said Dr. Dwight German, professor of psychiatry at UT Southwestern and senior author of a study available online and in a future issue of Biological Psychiatry.

The researchers focused on a gene related to the neurotransmitter serotonin, one of the chemical messengers that nerves use to communicate with one another. Once specific nerve cells release serotonin, a molecule called the serotonin transporter (SERT) brings it back into the cell. Thus, serotonin has only a brief influence on the target neurons. Drugs that prevent this re-uptake, such as Prozac, are frequently used to treat patients with depression.

The serotonin transporter gene has two forms, or variants: short, or SERT-s, and long, SERT-l. A person can have two copies of the short gene, one copy each of the short and long, or two copies of the long gene. It is estimated that about 17 percent of the population has two copies of the SERT-s gene.

People carrying two SERT-s genes are more sensitive to emotional stimuli and more likely to experience depression than people with one or no SERT-s genes.

The researchers studied brains from 49 deceased people, with and without psychiatric illnesses. The brains were sliced thinly, the size of the pulvinar measured, the number of nerve cells counted, and the variety of each individual's SERT gene analyzed.

They found that subjects carrying two SERT-s genes had pulvinars that were 20 percent larger and contained 20 percent more nerve cells - about 1.5 million more - than subjects with either one or two SERT-l genes. Whether the person had a psychiatric disorder did not affect the size of the pulvinar.

Dr. German cautioned, however, that the entire brain is not simply larger in individuals carrying two copies of the SERT-s gene. Similar studies in other areas of the brain have found that the SERT-s gene is associated with certain areas of the brain being smaller.

"The brain is wired differently in people who have depression, and probably from the point of view of treatment, we should try to identify these people as early as possible and intervene before the 'hard-wiring' gets altered," Dr. German said.

Dr. Umar Yazdani, assistant instructor in the Center for Basic Neuroscience at UT Southwestern, also participated in the study, as did lead author Dr. Keith Young and other researchers from the Central Texas VA and Texas A&M University System Health Science Center.

The work was supported by the National Institute of Mental Health; the Veterans Administration; the Scott, Sherwood and Brindley Foundation; the Zigenbein Memorial Fund; and the Theodore and Vada Stanley Foundation.

Visit http://www.utsouthwestern.org/mentalhealth to learn more about
UT Southwestern’s clinical services in psychiatry.


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Media Contact: Aline McKenzie
214-648-3404
aline.mckenzie@utsouthwestern.edu

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