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

Fisher, Helen.L; Cohen-Woods, Sarah; Hosang, Georgina M.; Uher, Rudolf; Powell-Smith, Georgia; Keers, Robert; Tropeano, Maria; Korszun, Ania; Jones, Lisa; Jones, Ian; Owen, Mike; Craddock, Nick; Craig, Ian W.; Farmer, Anne E. and McGuffin, Peter. 2012. Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression. Journal of Affective Disorders, 136(1-2), pp. 189-193. ISSN 0165-0327 [Article]

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Abstract or Description

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.

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.

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.

Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference.

This study failed to find evidence of gene–environment interplay in recurrent clinical depression.

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stressful life events; unipolar depression; recurrent; serotonin transporter gene; gene–environment interaction; 5-HTTLPR

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January 2012Published

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Date Deposited:

23 Apr 2014 10:06

Last Modified:

30 Jun 2017 15:55

Peer Reviewed:

Yes, this version has been peer-reviewed.


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