title: Differential impact of serotonin transporter activity on temperament and behavior in persons with a family history of alcoholism in the Oklahoma Family Health Patterns Project.
abstract: BACKGROUND
  Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its potential impact on temperament and behavior in persons with a family history of alcoholism (FH+).
  
  
  METHODS
  We tested 314 healthy young adults (23.5 years of age, 57% female; 193 FH- and 121 FH+) enrolled in the Oklahoma Family Health Patterns project, a study of alcoholism risk in relation to temperament and behavioral dyscontrol. Dysphoria was assessed using the Eysenck neuroticism and Beck depression scales, and Cloninger's Tridimensional Personality Questionnaire. Risk taking was assessed with the Iowa Gambling Task (IGT) and Balloon Analogue Response Task (BART). All subjects were genotyped for a functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4).
  
  
  RESULTS
  FH+ subjects with the gain-of-function 5-HTTLPR genotype scored higher in neuroticism, harm avoidance, and symptoms of depression (p-values ≤ 0.03). No effect of 5-HTTLPR genotype was seen in FH-. FH+ carriers of the gain-of-function 5-HTTLPR genotype played to minimize their frequency of losses in the IGT, whereas FH- carriers played a balanced strategy (p < 0.003). No 5-HTTLPR effects were seen in the BART. Results were unaffected by sex, education, drug use, and antisocial characteristics.
  
  
  CONCLUSIONS
  The functional 5-HTTLPR polymorphism predicted significant variation in negative moods and poorer affect regulation in FH+ persons, with possible consequences for behavior, as seen in a simulated gambling task. This pattern may contribute to a drinking pattern that is compensatory for such affective tendencies.
authors.affiliation: Department of Psychiatry and Behavioral Sciences , University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Behavioral Sciences Laboratories , Veterans Affairs Medical Center, Oklahoma City, Oklahoma.
authors.forename: William R
authors.initials: WR
authors.lastname: Lovallo
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: Eldad
authors.initials: E
authors.lastname: Yechiam
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.forename: Ashley
authors.initials: A
authors.lastname: Acheson
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Sorocco
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: Bojeong
authors.initials: B
authors.lastname: Kim
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cohoon
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Vincent
authors.forename: David
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000235:genetics; D009825:Oklahoma / Q000453:epidemiology; D010555:Personality Inventory; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012309:Risk-Taking; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013694:Temperament; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Anxiety; Depression; Family History of Alcoholism; Serotonin Transporter