Modulation
of stress-induced depression by a serotonin
transporter genotype
Stressful
events, such as losing a loved one or a job, are
well known precipitating factors of major
depression. The serotonin (5-hydroxytryptamine,
5-HT) transporter (5-HTT) gene codes for the
transport protein which is blocked by most
antidepressants and is thought to be central to
their mode of action. There are two forms
(alleles) of the 5-HTT gene, a long and a short
form. Animal studies and human functional
neuroimaging have suggested that the 5-HTT
genotype may be associated with responses to
stressful conditions. A recent study
investigated why some people adapt to stressful
events while others become depressed in relation
to the 5HTT genotype.
Among the 847 adults enrolled in this
prospective, longitudinal study, 147 were
homozygous for the short allele of the
5-HTT gene, 265 were homozygous for the
long allele, and 435 were heterozygous. The
subjects were born in the early 1970s were
followed from birth into their mid 20s and
stressful life events noted.
Among individuals with at least one copy of the
short form of 5-HTT who suffered four or more
stressful life events, 43% developed depressive
symptoms by age 26. This compared to 17% who had
two long alleles. Similar results were found for
diagnosis of major depression and
suicidality.
This study provides evidence of a direct genetic
link between stress and depression, people with
the short allele of the 5-HTT gene being more
vulnerable to depression after traumatic events.
The discovery of a group of individuals
(homozymous for the long allele) who are
protected against stressful life events could be
the beginning of a therapeutic strategy with the
objective of preventing depression. Science
301: 386-389, 2003