title: Differential susceptibility to prevention: GABAergic, dopaminergic, and multilocus effects.
abstract: BACKGROUND
  Randomized prevention trials provide a unique opportunity to test hypotheses about the interaction of genetic predispositions with contextual processes to create variations in phenotypes over time.
  
  
  METHODS
  Using two longitudinal, randomized prevention trials, molecular genetic and alcohol use outcome data were gathered from more than 900 youths to determine whether prevention program participation would, across 2 years, moderate genetic risk for increased alcohol use conferred by the dopaminergic and GABAergic systems.
  
  
  RESULTS
  We found that (a) variance in dopaminergic (DRD2, DRD4, ANKK1) and GABAergic (GABRG1, GABRA2) genes forecast increases in alcohol use across 2 years, and (b) youths at genetic risk who were assigned to the control condition displayed greater increases in alcohol use across 2 years than did youths at genetic risk who were assigned to the prevention condition or youths without genetic risk who were assigned to either condition.
  
  
  CONCLUSIONS
  This study is unique in combining data from two large prevention trials to test hypotheses regarding genetic main effects and gene × prevention interactions. Focusing on gene systems purported to confer risk for alcohol use and abuse, the study demonstrated that participation in efficacious prevention programs can moderate genetic risk. The results also support the differential susceptibility hypothesis that some youths, for genetic reasons, are more susceptible than others to both positive and negative contextual influences.
authors.affiliation: Center for Family Research, Institute for Behavioral Research, University of Georgia, Athens, GA 30602-4527, USA. gbrody@uga.edu
authors.forename: Gene H
authors.initials: GH
authors.lastname: Brody
authors.forename: Yi-fu
authors.initials: YF
authors.lastname: Chen
authors.forename: Steven R H
authors.initials: SR
authors.lastname: Beach
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology / Q000523:psychology; D000428:Alcohol Drinking / Q000235:genetics* / Q000517:prevention & control; D000437:Alcoholism / Q000235:genetics* / Q000517:prevention & control; D002648:Child; D004298:Dopamine / Q000235:genetics* / Q000502:physiology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D011954:Receptors, Dopamine / Q000235:genetics / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology; D012306:Risk
chemical_list: D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D004298:Dopamine
keywords: African American; Alcohol use; genetics; prevention; risk