Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample.
- Authors
- Peyrot, Wouter J; Middeldorp, Christel M; Jansen, Rick; Smit, Johannes H; de Geus, Eco J C; Hottenga, Jouke-Jan; Willemsen, Gonneke; Vink, Jacqueline M; Virding, Susanne; Barragan, Isabel; Ingelman-Sundberg, Magnus; Sim, Sarah C; Boomsma, Dorret I; Penninx, Brenda W J H
- Year
- 2013
- Journal
- Journal of affective disorders
- PMID
- 23021380
- DOI
- 10.1016/j.jad.2012.08.044
BACKGROUND: There is ongoing interest in the possible interaction of the serotonin-transporter-linked polymorphic region (5-HTTLPR) with environmental factors in determining Major Depressive Disorder (MDD). The current study contributes to this research area by comprehensively examining the interaction-effects and direct-effects of 5-HTTLPR and five environmental factors on MDD prevalence and course in a well-characterized longitudinal sample. METHODS: The sample consisted of 1625 patients with a CIDI-confirmed diagnosis of MDD and 1698 screened controls from the Netherlands. Four MDD outcomes were studied as dependent variables: one main MDD prevalence-outcome (all MDD), two more severe MDD prevalence-outcomes (suicidal and chronic MDD), and one MDD course outcome (chronic versus non-chronic MDD). Because SNP rs25531 modifies the effect of 5-HTTLPR, haplotypes of 5-HTTLPR and rs25531 were measured. For the four MDD outcome measures, we examined the direct effects of 5-HTTLPR/rs25531-haplotypes, five environmental factors (lifetime and recent stressful life-events, sexual abuse, low educational attainment, and childhood trauma) and their interaction in logistic regression models. RESULTS: The environmental factors had large and consistent effects on all four MDD outcomes, including course of MDD. The 5-HTTLPR/rs25531-haplotype had a suggestive effect on course of MDD, but not on presence of MDD. Gene-by-environment interaction was significant (<0.05) for one of the 20 tests performed, which is not more than expected by chance. LIMITATIONS: Environmental factors were not assessed before the onset of MDD. CONCLUSIONS: Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. | 2018 | 28373689 |
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