title: The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation.
abstract: BACKGROUND
  Two recent meta-analyses assessed the set of studies exploring the interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and stress in the development of depression and concluded that the evidence did not support the presence of the interaction. However, even the larger of the meta-analyses included only 14 of the 56 studies that have assessed the relationship between 5-HTTLPR, stress, and depression.
  
  
  OBJECTIVE
  To perform a meta-analysis including all relevant studies exploring the interaction.
  
  
  METHODS
  We identified studies published through November 2009 in PubMed.
  
  
  METHODS
  We excluded 2 studies presenting data that were included in other larger studies.
  
  
  METHODS
  To perform a more inclusive meta-analysis, we used the Liptak-Stouffer z score method to combine findings of primary studies at the level of significance tests rather than the level of raw data.
  
  
  RESULTS
  We included 54 studies and found strong evidence that 5-HTTLPR moderates the relationship between stress and depression, with the 5-HTTLPR s allele associated with an increased risk of developing depression under stress (P = .00002). When stratifying our analysis by the type of stressor studied, we found strong evidence for an association between the s allele and increased stress sensitivity in the childhood maltreatment (P = .00007) and the specific medical condition (P = .0004) groups of studies but only marginal evidence for an association in the stressful life events group (P = .03). When restricting our analysis to the studies included in the previous meta-analyses, we found no evidence of association (Munafò et al studies, P = .16; Risch et al studies, P = .11). This suggests that the difference in results between meta-analyses was due to the different set of included studies rather than the meta-analytic technique.
  
  
  CONCLUSIONS
  Contrary to the results of the smaller earlier meta-analyses, we find strong evidence that the studies published to date support the hypothesis that 5-HTTLPR moderates the relationship between stress and depression.
authors.affiliation: Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Karg
authors.forename: Margit
authors.initials: M
authors.lastname: Burmeister
authors.forename: Kerby
authors.initials: K
authors.lastname: Shedden
authors.forename: Srijan
authors.initials: S
authors.lastname: Sen
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002649:Child Abuse / Q000523:psychology; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D015870:Gene Expression / Q000235:genetics; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012931:Social Environment
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins