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/day of oral NTX or placebo. 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 placebo, p=0.007 and p=0.049, respectively). In contrast, for subjects with one or two L′ alleles, the effects of the more intensive psychosocial treatment (MBSCT) or NTX did not significantly differ from BBCET or placebo. Conclusions These preliminary findings support the utility of the 5-HTTLPR polymorphism for personalizing treatment selection in problem drinkers.

Effects of the serotonin transporter gene, sensitivity of response to alcohol, and parental monitoring on risk for problem alcohol use

“…In addition, for drinks consumed, this effect was also present at moderate monitoring levels. These results are consistent with prior studies finding that the 5-HTTLPR S allele is associated with negative alcohol behaviors and outcomes ( Chen et al, 2014 ; Covault et al, 2007 ; Herman et al, 2003 ), as well as those indicating that poorly monitored adolescents are more likely to use drugs ( Steinberg et al, 1994 ). Results also showed that at high levels of parental monitoring, the lower level of response to alcohol associated with the 5-HTTLPR S allele was negatively associated with alcohol-related problems.…”

“…The results presented here are consistent with a substantial portion of the work involving alcohol outcomes, level of response, and variation in 5-HTTLPR. Several empirical studies and two meta-analyses point to S carriers being at increased risk for negative alcohol outcomes (e.g., Chen et al, 2014 ; Feinn et al, 2005 ; Herman et al, 2003 ; McHugh et al, 2010 ). However, other studies have reported that L carriers are at increased risk (e.g., Hu et al, 2005 ; Schuckit et al, 1999 ).…”

“…Much of the prior work involving alcohol and 5-HTTLPR points to S carriers being at increased risk for negative alcohol outcomes, including more binge drinking occasions ( Chen et al, 2014 ; Herman, Philbeck, Vasilopoulos, & Depetrillo, 2003 ), more drinks per drinking occasion ( Covault et al, 2007 ), earlier age of drinking initiation ( Kaufman et al, 2007 ), and more frequent occasions of drinking with intentions to become intoxicated ( Covault et al, 2007 ). Two meta-analyses support this pattern of findings ( Feinn, Nellissery, & Kranzler, 2005 ; McHugh, Hofmann, Asnaani, Sawyer, & Otto, 2010 ); however, at least four studies have found the LL genotype to be the variant that confers alcohol-related risk ( Hinckers et al, 2006 ; Hu et al, 2005 ; Schuckit et al, 1999 ; Sen et al, 2004b ), and three studies found no association between 5-HTTLPR and alcohol risk ( Hill et al, 2002 ; Kranzler, Lappalainen, Nellissery, & Gelernter, 2002 ; Stoltenberg et al, 2002 ).…”

A scoping review of alcohol, tobacco, and other drug use treatment interventions for sexual and gender minority populations

“…Fifteen studies evaluated the impact of interventions on alcohol outcomes (Charlebois, Plenty, Lin, Ayala, & Hecht, 2017;Chavez & Palfai, 2019;Chen et al, 2014;Croff et al, 2012;Fals-Stewart, O'Farrell, & Lam, 2009;Kahler et al, 2018;Kuerbis, Schaumberg, Davis, Hail, & Morgenstern, 2014;Millar, Wang, & Pachankis, 2016;Morgenstern et al, 2007;Morgenstern et al, 2012;Santos et al, 2016;Santos et al, 2014;Smith et al, 2017;Velasquez et al, 2009;Wray, Kahler, Simpanen, & Operario, 2019). Nearly all of these studies (n=14) were conducted in the United States.…”

“…Of these, five were interventions to reduce alcohol consumption among SMM who engaged in heavy drinking (Chavez & Palfai, 2019;Kahler et al, 2018;Santos et al, 2016;Santos et al, 2014;Wray et al, 2019); two were designed to prevent or reduce heavy drinking among young SMM (Millar et al, 2016;Smith et al, 2017); four targeted SMM who engaged in both heavy and otherwise harmful drinking (i.e., negative consequences) (Chen et al, 2014;Morgenstern et al, 2012;Velasquez et al, 2009); and two focused on reducing alcohol consumption and preventing intoxication among bar patrons (Charlebois et al, 2017;Croff et al, 2012). (Chen et al, 2014;Kahler et al, 2018;Millar et al, 2016;Morgenstern et al, 2007;Morgenstern et al, 2012;Santos et al, 2016;Santos et al, 2014) and one on couple-level psychotherapy (Fals-Stewart et al, 2009). One study (Smith et al, 2017) evaluated a group intervention for young SMM, while another study (Charlebois et al, 2017) adopted a multi-pronged approach that included structural (i.e., physical environment), environmental (e.g., in-bar media campaign), and individual elements in a venue-based (gay bar) setting.…”