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. Mayoral, M. King, I. Nazareth, B. Gutiérrez, Miguel Xavier, Igor Slav, Heidi Ingrid Maaros, Jan Neelman, Francisco Torres-González, Irwing Nazareth, Michael King

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95 Citations (Scopus)

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)).

Original languageEnglish
Pages (from-to)748-755
Number of pages8
JournalMolecular Psychiatry
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Affective disorders
  • Gene-environment interaction
  • Primary care
  • Serotonin transporter gene polymorphism
  • SLC6A4
  • Social stress

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