title: 5-HTTLPR moderates naltrexone and psychosocial treatment responses in heavy drinking men who have sex with men.
abstract: BACKGROUND
  A functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene has been widely studied as a risk factor and moderator of treatment for a variety of psychopathologic conditions. To evaluate whether 5-HTTLPR moderates the effects of treatment to reduce heavy drinking, we studied 112 high-functioning European-American men who have sex with men (MSM). Subjects participated in a randomized clinical trial of naltrexone (NTX) and cognitive behavioral therapy (CBT) for problem drinking.
  
  
  METHODS
  Subjects were treated for 12 weeks with 100 mg/d of oral NTX or placebo (PBO). All participants received medical management with adjusted brief behavioral compliance enhancement treatment (BBCET) alone or in combination with modified behavioral self-control therapy (MBSCT; an amalgam of motivational interviewing and CBT). Participants were genotyped for the tri-allelic 5-HTTLPR polymorphism (i.e., low-activity S' or high-activity L' alleles).
  
  
  RESULTS
  During treatment, the number of weekly heavy drinking days (HDD; defined as 5 or more standard drinks per day) was significantly lower in subjects with the L'L' (N = 26, p = 0.015) or L'S' (N = 52, p = 0.016) genotype than those with the S'S' (N = 34) genotype regardless of treatment type. There was a significant interaction of genotype with treatment: For subjects with the S'S' genotype, the effects of MBSCT or NTX on HDD were significantly greater than the minimal intervention (i.e., BBCET or PBO, p = 0.007 and p = 0.049, respectively). In contrast, for subjects with 1 or 2 L' alleles, the effects of the more intensive psychosocial treatment (MBSCT) or NTX did not significantly differ from BBCET or PBO.
  
  
  CONCLUSIONS
  These preliminary findings support the utility of the 5-HTTLPR polymorphism for personalizing treatment selection in problem drinkers.
authors: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York; Research Foundation for Mental Hygiene, Inc., New York State Psychiatric Institute, New York, New York.
authors: Andrew C H
authors: AC
authors: Chen
authors: Christine M
authors: CM
authors: Davis
authors: Christopher W
authors: CW
authors: Kahler
authors: Alexis N
authors: AN
authors: Kuerbis
authors: Jonathan
authors: J
authors: Covault
authors: Henry R
authors: HR
authors: Kranzler
authors: Jon
authors: J
authors: Morgenstern
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology / Q000628:therapy*; D015928:Cognitive Behavioral Therapy / Q000379:methods; D018451:Homosexuality, Male / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D009271:Naltrexone
keywords: Men Who Have Sex With Men; Pharmacogenetics; Plasticity; Psychotherapy; Stress Reactivity