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Gene May Bias Amygdala Response to Frightful Faces

Press Release

The amygdala, the brain structure known as the hub of fear, responds differently to pictures of scary faces, depending on which version of a gene one has inherited, report National Institute of Mental Health (NIMH) scientists. Functional Magnetic Resonance Imaging (fMRI) scans revealed that subjects who inherited one or two copies of the short variant of the human serotonin transporter gene experienced greater activation of the amygdala when shown the pictures than those with two copies of the long variant of the gene. The gene's effect on the amygdala's response to emotional stimuli may help shape a dimension of temperament, suggest Drs. Ahmad Hariri and Daniel Weinberger, NIMH Clinical Brain Disorders Branch, and colleagues, in the July 19, 2002 Science.

"How biologically reactive we are to a signal of danger, which is partly heritable, can place us at risk for an anxiety disorder or it may be an adaptive, positive attribute, such as increased vigilance, depending on the circumstances," explained Weinberger. "Anxiety is a complex experience not caused by any one gene or environmental factor. By showing how a variation in a gene exerts its influence on the brain's center for fear processing, this finding may lend credence to earlier reports linking the short gene variant to slightly higher levels of anxiety. It provides potential insight into one factor that contributes to the way people experience emotion."

Each of us inherits two copies of the transporter gene for the chemical messenger serotonin, one from each parent. It codes for the protein in neurons that recycles secreted serotonin from the synapse. Serotonin reuptake inhibitors (SSRIs), the most widely prescribed medications for anxiety and depression, act by blocking the transporter. The two common genetic variations occur in a region of the gene that acts like a dimmer switch, controlling the level of the gene's turning on and off. This leads to transporter proteins that function somewhat differently. The short variant makes less protein, resulting in increased levels of serotonin in the synapse and more binding of the neurotransmitter to receptors on connecting neurons.

In the fMRI paradigm, developed by Hariri and colleagues, 28 subjects performed a facial emotion-matching task on a computer screen while their brain activity was scanned. They matched one of two faces that appeared at the bottom of the screen having the same emotion—angry or afraid—expressed on a face at the top of the screen (see graphic). This task is known to activate the amygdala, a small almond-shaped structure deep in the brain that processes fearful stimuli. Those with one or two copies of the short gene variant showed greater activation of the amygdala on the right side of the brain, which is specialized for processing faces (see graphic below). When the subjects performed a thinking task that did not involve emotional processing and the amygdala, no effects of the gene variants were seen.

The current study did not detect any differences in anxiety traits traceable to the serotonin transporter gene variants, perhaps because the sample was too small. Earlier studies by Dennis Murphy, M.D., NIMH, and colleagues, found that the variants accounted for three to four percent of the variance in anxiety traits. A few other studies using behavioral measurements have since turned up similar results, but the research has remained controversial due to the relatively small effect sizes.

"The fMRI study takes the genetic analysis forward to the level of neurobiology, closing one more link in the chain of causality between a functional difference in a gene and a complex behavior," noted David Goldman, M.D., National Institute on Alcohol Abuse and Alcoholism (NIAAA), one of the study authors.

Differences seen in adult subjects may be rooted in early postnatal developmental processes, early critical periods in which the gene variants may affect the course of emotional development and temperament, the journal article suggests.

Also participating in the research were Drs. Venkata Mattay, Alessandro Tessitore, Bhaskar Kolachana, Francesco Fera, and Michael Egan, NIMH.


Amygdala activation is subjects brain

Subjects who inherited one or two copies of the short variant of the human serotonin transporter gene experienced greater activation of the amygdala (circled in white) when shown pictures of scary faces than those with two copies of the long variant of the gene. Functional magnetic resonance imaging data (red) superimposed on structural MRI scan cross section shows areas of difference in amygdala activation between the two groups.

Results of motion matching test

While their brain activity was being scanned, subjects performed an emotion matching task known to activate the amygdala. They were asked to select, from the two faces at the bottom of the screen, the one that expressed the same emotion (angry or afraid) as the face at the top.

MRI rendering of brain

3-D MRI rendering of a brain with fMRI activation of the amygdala highlighted in red.

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About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website .