Serotonin Transporter Genotype Linked to Adolescent Substance Use Treatment Outcome through Externalizing Behavior.

Tammy Chung,Jack R Cornelius,Christopher S Martin,Duncan B Clark,Robert Ferrell,Stephen A Maisto

doi:10.3389/fped.2014.00071

Tammy Chung, Jack R Cornelius + Show 4 more

Open Access

https://doi.org/10.3389/fped.2014.00071

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Abstract

Meta-analyses suggest that the serotonin transporter linked polymorphic region (5-HTTLPR) short (S) allele, relative to the long (L) allele, is associated with risk for alcohol dependence, particularly among individuals with early onset antisocial alcoholism. Youth in substance use treatment tend to show antisocial or externalizing behaviors, such as conduct problems, which predict worse treatment outcome. This study examined a pathway in which 5-HTTLPR genotype is associated with externalizing behavior, and the intermediate phenotype of externalizing behavior serves as a link between 5-HTTLPR genotype and substance use treatment outcome in youth. Adolescents (n = 142) who were recruited from addictions treatment were genotyped for 5-HTTLPR polymorphisms (S and LG carriers vs. LALA), assessed for externalizing and internalizing behaviors shortly after starting treatment, and followed over 6-months. 5-HTTLPR genotype was not associated with internalizing behaviors, and was not directly associated with 6-month substance use outcomes. However, 5-HTTLPR genotype was associated with externalizing behaviors (S and LG > LALA), and externalizing behaviors predicted alcohol and marijuana problem severity at 6-month follow-up. Results indicated an indirect (p < 0.05) and non-specific (i.e., both alcohol and marijuana severity) effect of 5-HTTLPR genotype on youth substance use treatment outcomes, with externalizing behaviors as an important linking factor. Adolescents in substance use treatment with low expressing (S and LG) 5-HTTLPR alleles and externalizing behavior might benefit from intervention that addresses serotonergic functioning, externalizing behaviors, and substance use to improve outcomes.

Highlights

Serotonergic functioning has been associated with externalizing behaviors, such as conduct problems and aggression; internalizing behaviors, such as depression and anxiety [1]; and substance use [2]
TESTING AN INDIRECT PATHWAY LINKING 5-HTTLPR GENOTYPE AND TREATMENT OUTCOME Preliminary bivariate correlations supported a possible mediation (“indirect”) pathway involving an association between 5HTTLPR low vs. high expressing genotype and externalizing behavior (r = 0.21, p = 0.01), and externalizing behavior with 6month alcohol and marijuana-related problems (RAPI r = 0.30, p < 0.01; RMPI = 0.27, p < 0.01)
Results supported the hypothesis that low, relative to high, expressing 5-HTTLPR genotype would be associated with greater externalizing behavior among youth in substance use treatment

Summary

Introduction

Serotonergic functioning has been associated with externalizing behaviors, such as conduct problems and aggression; internalizing behaviors, such as depression and anxiety [1]; and substance use [2]. Serotonin transporter genotype may be more strongly associated with intermediate phenotypes of externalizing and internalizing behaviors, than with a substance use phenotype, because the intermediate phenotypes often manifest prior to substance use behavior. Among adolescents in substance use treatment, externalizing behaviors robustly predict worse outcomes [5]. Based on these observations, this study of adolescent substance users tested a pathway in which serotonin transporter genotype is associated with externalizing and internalizing behaviors as intermediate phenotypes, and the intermediate phenotypes provide a link between serotonin transporter genotype and substance use treatment outcomes. Increased understanding of how a genetic marker is associated with treatment outcome could help to guide the development of personalized interventions [6]

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