Sensitivity
of the serotonin transporter gene to the
depressogenic effects of stressful life
events
The
onset of major depression is frequently preceded
by stressful life events. The response of humans
to adversity is, however, variable, some being
stress-sensitive in response to mild stressors
and prone to depression, while others are
stress-resistant in the face of severe
adversity. Studies have examined the possible
genes responsible for this different
differential response to stress. Among candidate
genes, a functional length polymorphism in the
promoter of the serotonin (5-HT) transporter
(5-HTT) gene could be involved and has been the
aim of a recent study.
A population-based sample of 549 male and female
twins (mean age 34.9 years) participated in the
study. The risk for major depression and
generalised anxiety syndrome in the last year
was evaluated as a function of 5-HTT genotype,
sex and the stressful life events. A sample of
buccal cells from the subjects and polymerase
chain reaction were used for genomic DNA
analysis to determine the presence of the short
allele (S) and long allele (L), and the
frequency of the 3 genotypes, SS, SL, and
LL.
Subjects with short alleles (SS) had greater
sensitivity to the depressogenic effect of
stressful life events compared with those with
one (SL) or two (LL) long alleles. The risk for
major depression increased with higher levels of
stress, and was greater in females than in males
at every level of stress and genotype. The risk
for onset of depression was less for individuals
with SL or LL genotypes when they experienced a
stressful life event with a mild level of threat
compared with no stress event. For SS subjects
the risk was more than 8 times greater with a
mild or low-moderate threat event compared with
months without stress event. The
5-HTT genotype had no influence on the risk
of developing generalised anxiety syndrome.
These data confirm and extend previous results
showing that a functional variant in the 5-HTT
play a role in the different response of
individuals to the impact of stressful life
events on the onset of depression, the SS
genotype leading to a greater sensitivity to
stress. Kendler
KS, Kuhn JW, Vittum J, Prescott CA, Riley B. The
interaction of stressful life events and a
serotonin transporter polymorphism in the
prediction of episodes of major depression: a
replication. Arch Gen Psychiatry 2005,
62:529-535.