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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.

Abstract：

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.

journal_name

J Affect Disord

journal_title

Journal of affective disorders

authors

Peyrot WJ,Middeldorp CM,Jansen R,Smit JH,de Geus EJ,Hottenga JJ,Willemsen G,Vink JM,Virding S,Barragan I,Ingelman-Sundberg M,Sim SC,Boomsma DI,Penninx BW

doi

10.1016/j.jad.2012.08.044

subject

Has Abstract

pub_date

2013-03-20 00:00:00

pages

91-9

issue

eissn

0165-0327

issn

1573-2517

pii

S0165-0327(12)00615-5

journal_volume

146

pub_type

杂志文章

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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.