If a person possesses a very common variant of a serotonin transporter gene
and encounters stressful events, he or she may well develop symptoms of
anxiety or depression, research findings have suggested.
The gene variant and stressful events may conspire to spark anxiety or
depression by supercharging a brain region crucial for fear
The study was conducted by Daniel Weinberger, M.D., director of the genes,
cognition, and psychosis program at the National Institute of Mental Health,
and by other scientists participating in the program. Results appeared in the
February Archives of General Psychiatry.
The 5-HT transporter protein plays a vital role in nerve transmission
involving the neurotransmitter serotonin. The gene that makes the transporter
has two variants—a short one and a long one. Persons possessing either
one or two copies of the short variant are more prone to anxiety and
depression, at least in the wake of stressful events, than are persons
possessing two copies of the long variant.
Thus Weinberger and his coworkers decided to conduct a study to determine
whether the means by which stressful events lead to anxiety and depression in
persons with one or two copies of the short gene variant is via activation of
the amygdala, since that brain area is crucial for fear responses and other
Their study included 92 subjects of the same ethnic background (European
American) who did not have a psychiatric disorder to eliminate the possibility
that ethnicity might confound results. All of the subjects were screened to
see which of the two 5-HT transporter gene variants they possessed.
Twenty-seven (29 percent) had two copies of the long variant, and 65 (71
percent) had at least one copy of the short variant. These percentages
corresponded to those usually found in Americans of European backgrounds.
All of the subjects were asked to engage in a simple perceptual task known
to robustly engage the amygdala. It involved matching fearful and angry facial
While the subjects undertook the task, Weinberger and his team visualized,
with functional MRI scans, the activity of their left and right amygdalae. The
researchers then looked to see whether there was any difference in amygdala
activity between the subjects with the short gene variant and those with the
long gene variant.
They found that subjects with one or more copies of the short gene variant
experienced significantly more activity in the right amygdala than did
subjects with the long gene variant. (In contrast, there was no difference in
left amygdala activity between the two groups.)
Thus, "Our results reveal a potent modulatory effect of the [short
gene variant] on amygdala reactivity to environmental threat," the
researchers concluded. "[The short gene variant] may represent a classic
susceptibility factor for affective disorders by biasing the functional
reactivity of the human amygdala in the context of stressful life
On the other hand, since both men and women with the short gene variant
were found to experience heightened right amygdala activity, possession of the
short gene variant alone cannot explain women's greater susceptibility to
anxiety and depression, the researchers noted.
An abstract of the study report, "A Susceptibility Gene for
Affective Disorders and the Response of the Human Amygdala," is posted
Arch Gen Psychiatry20052146