Effects of the serotonin transporter gene, sensitivity of response to alcohol, and parental monitoring on risk for problem alcohol use.
- Authors
- Cope, Lora M; Munier, Emily C; Trucco, Elisa M; Hardee, Jillian E; Burmeister, Margit; Zucker, Robert A; Heitzeg, Mary M
- Year
- 2017
- Journal
- Alcohol (Fayetteville, N.Y.)
- PMID
- 28262188
- DOI
- 10.1016/j.alcohol.2016.12.001
- PMCID
- PMC5340078
The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) has been previously associated with alcohol-related risk. Most findings point to short (S) allele carriers being at increased risk for negative alcohol outcomes relative to long allele homozygotes, although some work indicates a more complex relationship. The current prospective study aimed to clarify how and under what circumstances variations in 5-HTTLPR transmit risk for various alcohol-related outcomes. Participants were 218 adolescents and young adults (29% female) enrolled in the Michigan Longitudinal Study. We tested a moderated mediation model with 5-HTTLPR as the predictor, Self-Rating of the Effects of Alcohol (SRE) score as the mediator, alcohol-related outcomes as the dependent variables, parental monitoring as the moderator of the SRE to alcohol outcomes path, and prior drinks, sex, age, and body mass index as covariates. Four alcohol-related outcomes were tested. The S allele was associated with higher SRE scores (i.e., lower response to alcohol). Parental monitoring was a significant moderator: At low levels of parental monitoring, higher SRE scores predicted more drinks consumed and binge drinking episodes. At high levels of monitoring, higher SRE scores were significantly related to fewer alcohol-related problems. Findings suggest that one mechanism by which 5-HTTLPR variation transmits alcohol-related risk is through level of response to alcohol. Furthermore, the strength and direction of this effect varied by level of parental monitoring, indicating that even in the presence of genetic and physiological vulnerability, parents can influence the likelihood of offspring developing problematic alcohol-related behaviors.
Conceptual diagram of conditional process modelA conceptual diagram of the model testing whether the mediated effect of 5-HTTLPR genotype on alcohol outcomes through level of response (SRE-5) is contingent on parental monitoring, controlling for drinks before SRE-5 assessment, sex, age at SRE-5 assessment, and BMI. 5-HTTLPR, serotonin transporter-linked polymorphic region of the serotonin transporter gene (SLC6A4); SRE-5, Self-Rating of the Effects of Alcohol (first five drinking occasions; standardized person-mean imputation method [Lee et al., 2015]); BMI, body mass index.
Statistical Diagram of Conditional Process ModelA statistical diagram of the model testing whether the mediated effect of 5-HTTLPR genotype on alcohol outcomes through level of response (SRE-5) is contingent on parental monitoring, controlling for drinks before SRE-5 assessment, sex, age at SRE-5 assessment, and body mass index (BMI; covariates not depicted in figure). Letters correspond to path labels in Table 3. 5-HTTLPR, serotonin transporter-linked polymorphic region of the serotonin transporter gene (SLC6A4); SRE-5, Self-Rating of the Effects of Alcohol (first five drinking occasions; standardized person-mean imputation method [Lee et al., 2015]).
Interaction of SRE-5 × Parental Monitoring Predicting Drinks per YearA visual depiction of the moderated mediation effect (interaction only; i.e., the simple slopes of SRE-5 predicting drinks per year at low, moderate, and high levels of parental monitoring, controlling for 5-HTTLPR and drinks before SRE-5 assessment, sex, age at SRE-5 assessment, and body mass index). Using the PROCESS macro, the conditional indirect effect of 5-HTTLPR was significant at low and moderate levels of parental monitoring (effects denoted with an *), with higher SRE-5 scores associated with a greater number of drinks per year. Drinks per year was square root transformed. 5-HTTLPR, serotonin transporter-linked polymorphic region of the serotonin transporter gene (SLC6A4); SRE-5, Self-Rating of the Effects of Alcohol (first five drinking occasions; standardized person-mean imputation method [Lee et al., 2015]).
Interaction of SRE-5× Parental Monitoring Predicting Binge Drinking Days per YearA visual depiction of the moderated mediation effect (interaction only; i.e., the simple slopes of SRE-5 predicting binge drinking days per year at low, moderate, and high levels of parental monitoring, controlling for 5-HTTLPR and drinks before SRE-5 assessment, sex, age at SRE-5 assessment, and body mass index). Using the PROCESS macro, the conditional indirect effect of 5-HTTLPR was significant at low levels of parental monitoring (effect denoted with an *), with higher SRE-5 scores associated with a greater number of binge drinking days per year. Binge drinking days per year was square root transformed. 5-HTTLPR, serotonin transporter-linked polymorphic region of the serotonin transporter gene (SLC6A4); SRE-5, Self-Rating of the Effects of Alcohol (first five drinking occasions; standardized person-mean imputation method [Lee et al., 2015]).
Interaction of SRE-5 × Parental Monitoring Predicting Alcohol-Related Problems per YearA visual depiction of the moderated mediation effect (interaction only; i.e., the simple slopes of SRE-5 predicting alcohol-related problems per year at low, moderate, and high levels of parental monitoring, controlling for 5-HTTLPR and drinks before SRE-5 assessment, sex, age at SRE-5 assessment, and body mass index). Using the PROCESS macro, the conditional indirect effect of 5-HTTLPR was significant at high levels of parental monitoring (effect denoted with an *), with higher SRE-5 scores associated with fewer alcohol-related problems per year. Alcohol-related problems per year was square root transformed. 5-HTTLPR, serotonin transporter-linked polymorphic region of the serotonin transporter gene (SLC6A4); SRE-5, Self-Rating of the Effects of Alcohol (first five drinking occasions; standardized person-mean imputation method [Lee et al., 2015]).
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