A collaborative study in the US has uncovered perhaps
the strongest evidence yet linking variation in a particular gene with
Researchers from Massachusetts General Hospital (MGH),
the University of California at San Diego, and Yale University says that
particular versions of a gene that affects the activity of important
neurotransmitter receptors were more common in both children and adults
assessed as being inhibited or introverted, and also were associated with
increased activity of brain regions involved in emotional processing.
"We found that variations in this gene were associated
with shy, inhibited behaviour in children, introverted personality in adults
and the reactivity of brain regions involved in processing fear and anxiety.
Each of these traits appears to be a risk factor for social anxiety disorder,
the most common type of anxiety disorder in the US," says Dr. Jordan Smoller of
the MGH Department of Psychiatry, the report's lead author.
It has long been recognized that the tendency to
anxiety disorders can run in families and is believed to be influenced by the
interaction of several genes. Given the varied forms of such disorders and
their complex patterns of inheritance, identifying specific susceptibility
genes has been difficult.
Several mice studies have linked an area of chromosome
1 to anxious temperament, particularly the gene that codes for a protein called
RGS2, which mediates the activity of neurotransmitter receptors that are also
the targets of many antidepressant and antipsychotic drugs. Mice in whom RGS2
is knocked out exhibit increased fearful behaviour.
As part of the present research into the role of RGS2
in humans, the researchers conducted several experiments. They analysed blood
samples from children from 119 families who had participated in an earlier
study assessing their reactions to unfamiliar situations at the ages of 21
months, four and six years.
The research team evaluated the participants on their
levels of behavioural inhibition, a form of temperament linked to increased
risk of anxiety disorders. While testing several sites in the RGS2 gene, they
identified nine variations that appeared to be associated with inhibition.
In another experiment, over 700 college students were
assigned to complete questionnaires designed to measure several personality
traits. The researchers analysed blood samples from the group, and genotyped
the four gene markers that had demonstrated the strongest effects in the first
The team observed that the versions associated with
inhibited behaviour in the children were also more common in the college students
who scored high on measures of introversion, a personality trait that also
involves social inhibition.
Another group of 55 college students completed a
standard interview screening for anxiety and mood disorders, and, thereafter,
had functional MRI brain imaging done. While in the MR scanner, the
participants viewed a series of faces expressing various emotions, a test that
previously was shown to influence activity in the amygdala, a brain structure
involved in emotion processing.
The researchers revealed that participants with the
inhibition-associated alleles also had increased activity of the amygdala and
the insula, another anxiety-related brain region.
"Now we need to investigate whether these RGS2
variants actually are associated with particular disorders and how they act on
a cellular level. We hope that ultimately this work will lead to new drug
targets and treatment options for anxiety disorders," says Smoller.
A report on the study
has been published in the Archives of General Psychiatry.