5-HTTLPR moderates naltrexone and psychosocial treatment responses in heavy drinking men who have sex with men.

Abstract

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. 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). 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. These preliminary findings support the utility of the 5-HTTLPR polymorphism for personalizing treatment selection in problem drinkers.