title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands. w.peyrot@ggzingeest.nl
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: Peyrot
authors.forename: Christel M
authors.initials: CM
authors.lastname: Middeldorp
authors.forename: Rick
authors.initials: R
authors.lastname: Jansen
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Smit
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Vink
authors.forename: Susanne
authors.initials: S
authors.lastname: Virding
authors.forename: Isabel
authors.initials: I
authors.lastname: Barragan
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Sim
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics*; D004522:Educational Status; D005260:Female; D059647:Gene-Environment Interaction; D006239:Haplotypes; D006801:Humans; D008016:Life Change Events; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012742:Sex Offenses / Q000523:psychology
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins