title: Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health).
abstract: BACKGROUND
  The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive.
  
  
  METHODS
  We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995.
  
  
  RESULTS
  Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment.
  
  
  CONCLUSIONS
  Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Brett C
authors.initials: BC
authors.lastname: Haberstick
authors.affiliation: Institute of Behavioral Science, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Boardman
authors.affiliation: Department of Sociology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Brandon
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smolen
authors.affiliation: Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: John K
authors.initials: JK
authors.lastname: Hewitt
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Ley A
authors.initials: LA
authors.lastname: Killeya-Jones
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Joyce
authors.initials: J
authors.lastname: Tabor
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.|Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Carolyn T
authors.initials: CT
authors.lastname: Halpern
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Brummett
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Redford B
authors.initials: RB
authors.lastname: Williams
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Ilene C
authors.initials: IC
authors.lastname: Siegler
authors.affiliation: Department of Psychiatry, Health Sciences Center, University of Colorado, Denver, Colorado, United States of America.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hopfer
authors.affiliation: Department of Sociology, University of North Carolina, Chapel Hill, North Carolina, United States of America.|Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mullan Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002649:Child Abuse / Q000534:rehabilitation; D003863:Depression / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008016:Life Change Events; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D059020:Suicidal Ideation; D014481:United States
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins