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.
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 X(2)=4.7, P=0.09 (crude), LR-X(2)=6.4, P=0.04 (adjusted); ICD-10 severe depressive episode: LR X(2)=6.9, P=0.032 (crude), LR-X(2)=8.1, P=0.017 (adjusted)).
Cervilla
J A
JA
Departamento de Medicina Legal, Toxicología y Psiquiatría, Facultad de Medicina, Universidad de Granada, Granada, Spain. jacb@ugr.es
Molina
E
E
Rivera
M
M
Torres-González
F
F
Bellón
J A
JA
Moreno
B
B
Luna
J D
JD
Lorente
J A
JA
Mayoral
F
F
King
M
M
Nazareth
I
I
Gutiérrez
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008016:Life Change Events; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D012931:Social Environment; D012959:Socioeconomic Factors; D013030:Spain; D018709:Statistics, Nonparametric
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins