TY - JOUR
T1 - 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
AU - Peyrot, W.
AU - Middeldorp, C.M.
AU - Jansen, R.
AU - Smit, J.H.
AU - de Geus, E.J.C.
AU - Hottenga, J.J.
AU - Willemsen, G.
AU - Vink, J.M.
AU - Virding, S.
AU - Barragan, I.
AU - Ingelman-Sundberg, M.
AU - Sim, S.C.
AU - Boomsma, D.I.
AU - Penninx, B.W.J.H.
PY - 2013
Y1 - 2013
N2 - 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. © 2012 Elsevier B.V.
AB - 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. © 2012 Elsevier B.V.
U2 - 10.1016/j.jad.2012.08.044
DO - 10.1016/j.jad.2012.08.044
M3 - Article
SN - 0165-0327
VL - 146
SP - 91
EP - 99
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
IS - 1
ER -