The relationship of serotonin-transporter polymorphism and early life events with endophenotypes of depression and anxiety

A common polymorphism in the linked promoter region of the 5-HTT gene results
in variants that involve a homozygous short (ss) allele or a long (ll) allele
or a heterozygous (sl) allele. Individuals who carry one or two copies of the s
allele are found to have increased levels of extracellular serotonin compared
to those with two copies of the l allele, which may render them vulnerable to
depression (Heils et al., 1996); Lesch et al., 1996).
The s allele (genotype ss or sl) of the 5-HTT was shown to be associated with
higher scores on the personality trait of neuroticism (Lesch et al, 1996). But
over the years, replications of this finding have been ambiguous. Sen,
Burmeister and Ghosh (2005) tested 384 healthy subjects and were able to
replicate Lesch*s findings. Willis Owen et al (2005) found no support for the
link between the polymorphism and neuroticism in samples selected for
extremeness of neuroticism scores. A meta-analysis showed a small but reliable
influence of 5-HTT polymorphism on neuroticism (Schinka et al, 2004). Another
meta-analysis however showed no evidence for an association between the 5-HT
transporter and the scores on neuroticism scales (Munafo, 2003).

In this study we aim to investigate the possibility that part of the
inconsistency regarding the relationship between neuroticism and the 5-HTT
polymorphism is based on the moderating effect of early life trauma.
A second reason for the inconsistencies noted above may lie in the definition
of the endophenotype and conceptual problems with the concept of neuroticism.
We will therefore focus on more specific measures of vulnerability to
depression and anxiety as outcome measures.

Observational study.

Burden is very low. People are asked personal questions, but on paper. People
will be free to leave certain questions unanswered. Questionnaires have been
used extensively in prior research, also in vulnerable samples.