title: The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to psychosocial stress than L-allele homozygotes. This study aimed to investigate whether 5-HTTLPR genotype moderates the effects of stress on ADHD in a multisite prospective ADHD cohort study.
  
  
  METHODS
  5-HTTLPR genotype, as well as the number of stressful life events in the past 5 years and ongoing long-term difficulties, was determined in 671 adolescents and young adults with ADHD, their siblings, and healthy controls (57.4% male, average age 17.3 years). Linear mixed models, accounting for family relatedness, were applied to investigate the effects of genotype, experienced stress, and their interaction on ADHD severity at time point T2, while controlling for ADHD severity at T1 (mean follow-up time 5.9 years) and for comorbid internalizing problems at T2.
  
  
  RESULTS
  The interaction between genotype and stress significantly predicted ADHD severity at T2 (p = .006), which was driven by the effect on hyperactivity-impulsivity (p = .004). Probing of the interaction effect made clear that S-allele carriers had a significantly more positive correlation between stress and ADHD severity than L-allele homozygotes.
  
  
  CONCLUSIONS
  The results show that the interaction between 5-HTTLPR and stress is a mechanism involved particularly in the hyperactivity/impulsivity dimension of ADHD, and that this is independent of comorbid internalizing problems. Further research into the neurobiological mechanisms underlying this interaction effect is warranted.
authors.affiliation: Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: van der Meer
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Richards
authors.forename: Janita B
authors.initials: JB
authors.lastname: Bralten
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Jaap
authors.initials: J
authors.lastname: Oosterlaan
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Heslenfeld
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D006801:Humans; D008016:Life Change Events; D008297:Male; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D012720:Severity of Illness Index; D035781:Siblings; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: ADHD; gene-environment interaction (GxE); serotonin transporter (5-HTTLPR); stress