Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression

Helen Fisher, Sarah Cohen-Woods, Georgina Hosang, Rudolf Uher, Georgia Powell-Smith, Robert Keers, Maria Tropeano, Ania Korszun, Lisa Jones, Ian Jones, Michael Owen, Nick Craddock, Ian Craig, Anne Farmer, Peter McGuffin

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    19 Citations (Scopus)


    Background: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes. Method: A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6 months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. Results: A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models. The results were the same for men and women. Limitations: Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference. Conclusions: This study failed to find evidence of gene-environment interplay in recurrent clinical depression.

    Original languageEnglish
    Pages (from-to)189-193
    Number of pages5
    JournalJournal of Affective Disorders
    Issue number1-2
    Publication statusPublished - Jan 2012


    • 5-HTTLPR
    • Gene-environment interaction
    • Recurrent
    • Serotonin transporter gene
    • Stressful life events
    • Unipolar depression


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