The risk of depression conferred by stressful life events...
The risk
for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype:
evidence from the Spanish PREDICT-Gene cohort
J A Cervilla, E Molina,
M Rivera, F Torres-González, J A Bellón, B Moreno,
J D Luna, J A Lorente, F Mayora,
M King, I Nazareth
Received 19 September 2006; Revised 25 January 2007; Accepted 6 February 2007;
Published online 27 March 2007.
ABSTRACT
We report results from the PREDICT-Gene
case-control study nested in a prospective cohort designed to identify predictors of the onset of depression among adult primary-care
attendees. We tested the potential gene-by-environment interaction between 5HTTLPR genotype at the serotonin transporter gene
and previous exposure to threatening life events (TLEs) in depression. A total of 737 consecutively recruited participants
were genotyped. Additional information was gathered on exposure to TLEs over a 6-month period, socio-demographic data and
family history of psychological problems among first-degree relatives. Diagnoses of depression were ascertained using the
Composite International Diagnostic Interview (CIDI) by trained interviewers. Two different depressive outcomes were used (ICD-10
depressive episode and ICD-10 severe depressive episode). Both the s/s genotype and exposure to increasing number of TLEs
were significantly associated with depression. Moreover, the 5HTTLPR s/s genotype significantly modified the risk conferred
by TLEs for both depressive outcomes. Thus, s/s homozygous participants required minimal exposure to TLE (1 TLE) to acquire
a level of risk for depression that was only found among l/s or l/l individuals after significantly higher exposure to TLEs
(two or more TLEs). The interaction was more apparent when applied to the diagnosis of ICD-10 severe depressive episode and
after adjusting for gender, age and family history of psychological problems. Likelihood ratios tests for the interaction
were statistically significant for both depressive outcomes (ICD-10 depressive episode: LR X2=4.7, P=0.09
(crude), LR-X2=6.4, P=0.04 (adjusted); ICD-10 severe depressive episode: LR X2=6.9,
P=0.032 (crude), LR-X2=8.1, P=0.017 (adjusted)).
