title: 5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder.
abstract: BACKGROUND
  Antisocial personality disorder (ASPD) frequently co-occurs with substance dependence (SD). A functional polymorphism (5-HTTLPR) in the serotonin transporter gene has been widely studied as a risk factor for a variety of psychopathologic conditions including aggressive/violent behavior. Childhood abuse is an important predictor of ASPD. We examined 5-HTTLPR genotype and adverse childhood events (ACEs) as risk factors for ASPD in a SD sample.
  
  
  METHODS
  Study participants [602 European-Americans (EAs) and 779 African-Americans (AAs)] were interviewed to obtain lifetime diagnoses of ASPD and SD and information on ACEs. Triallelic genotypes for 5-HTTLPR were obtained using standard methods. We used logistic generalized estimating equations regression to examine ACEs and 5-HTTLPR genotype and their interaction as predictors of ASPD, separately by population group.
  
  
  RESULTS
  There were 203 (14.7%) participants diagnosed with ASPD. The frequency of the low-activity 5-HTTLPR S' allele did not differ by ASPD diagnosis, and there was no overall 5-HTTLPR×ACE interaction. However, among European-Americans, male sex (odds ratio=3.36; P<0.001) and ACE history (odds ratio=1.47; P=0.002) were significant predictors of ASPD. Among AAs, there was a significant interaction of sex×5-HTTLPR genotype×ACEs (χ=13.92, P<0.001). Among AA men, each additional ACE significantly increased the odds of ASPD irrespective of genotype, whereas among AA women, the effect of ACEs on ASPD was significant only among S' homozygotes. However, these results are limited by the small sample size in each subgroup, (particularly AA women with S'S' genotype; N=7) and require replication.
  
  
  CONCLUSIONS
  Childhood maltreatment contributes to the risk of ASPD, an effect for which there is preliminary evidence of moderation by 5-HTTLPR genotype in AA women.
authors.affiliation: Department of Psychiatry, University of Connecticut School of Medicine, Farmington, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Douglas
authors.forename: Grace
authors.initials: G
authors.lastname: Chan
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Arias
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Anton
authors.forename: James
authors.initials: J
authors.lastname: Poling
authors.forename: Lindsay
authors.initials: L
authors.lastname: Farrer
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000987:Antisocial Personality Disorder / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002649:Child Abuse; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins