title: Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: replications and implications for resolving inconsistent results.
abstract: BACKGROUND
  Genetic and environmental factors shape life-long vulnerability to depression, but most gene-environment interaction (G×E) research has focused on cross-sectional assessments rather than life-course phenotypes. This study tests the hypothesis that the G×E involving the length polymorphism in the serotonin-transporter-gene-linked-promoter-region (5-HTTLPR) and childhood maltreatment is specific to depression that runs a persistent course in adulthood.
  
  
  METHODS
  The hypothesis is tested in two cohorts. Men and women in the Dunedin Study (N=847), New Zealand, followed to age 32 years with 96% retention and women in the E-Risk Study (N=930), England, followed to age 40 years with 96% retention. Diagnoses of past-year major depressive episode were established at four separate assessments. Depression diagnosed on two or more occasions was considered persistent.
  
  
  RESULTS
  In both cohorts, statistical tests of gene-environment interactions showed positive results for persistent depression but not single-episode depression. Individuals with two short 5-HTTLPR alleles and childhood maltreatment had elevated risk of persistent but not single-episode depression.
  
  
  CONCLUSIONS
  Some cases of recurrent depression may have been misclassified as single-episode due to non-contiguous assessment windows, but this would have a conservative effect on the findings. Chronic and recurrent depression could not be reliably distinguished due to non-contiguous periods of assessment. Therefore, the term persistent depression is used to describe either chronic or recurrent course.
  
  
  CONCLUSIONS
  The specific effect on persistent depression increases the significance of this G×E for public health. Research that does not distinguish persistent course may underestimate G×E effects and account for some replication failures in G×E research.
authors: Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK. rudolf.uher@kcl.ac.uk
authors: Rudolf
authors: R
authors: Uher
authors: Avshalom
authors: A
authors: Caspi
authors: Renate
authors: R
authors: Houts
authors: Karen
authors: K
authors: Sugden
authors: Benjamin
authors: B
authors: Williams
authors: Richie
authors: R
authors: Poulton
authors: Terrie E
authors: TE
authors: Moffitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D002675:Child, Preschool; D003863:Depression / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics; D004739:England; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D009520:New Zealand; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011634:Public Health; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins