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Thursday, July 18, 2002
2:00 p.m. EDT
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 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, 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
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 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.
NIMH and NIAAA are part of the National Institutes of Health (NIH), the Federal
Government's primary agency for biomedical and behavioral research. NIH is a
component of the U.S. Department of Health and Human Services.
For more information, contact NIMH press office, 301-443-4536, NIAAA press
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.
3-D MRI rendering of a brain with fMRI activation
of the amygdala highlighted in red.