Associations of the dopamine D4 receptor gene VNTR polymorphism with drug use in adolescent psychiatric inpatients

Abstract

Background-The VNTR polymorphism in the Dopamine D4 receptor gene (DRD4) has been associated with differential urge for substances across multiple methodologies ranging from neuroimaging to assessment in the natural environment. It is unclear whether the DRD4 gene is a marker for an underlying propensity for greater urge or whether the DRD4 gene differentially moderates the neuroadaptive effects of extended substance use on urge. Examination of the DRD4 in an adolescent sample may provide evidence of a mechanism of this putative relationship.

Genetic Addiction Risk Score (GARS): Testing For Polygenetic Predisposition and Risk to Reward Deficiency Syndrome (RDS)

“…This reduced sensitivity or "dopamine resistance" leads to hypodopaminergic functioning. Thus 7R VNTR has been associated with substance-seeking behavior (McGeary et al, 2007). Survival analysis has revealed that by 25 years of age 76% of subjects with a DRD4 7-repeat allele have significantly more persistent ADHD compared with 66% of subjects without the risk allele.…”

Genetic, personality, and environmental predictors of drug use in adolescents

“…This reduced sensitivity to dopamine leads to hypodopaminergic functioning. The 7R VNTR has been associated with drug use disorders (McGeary, Esposito-Smythers, Spirito, & Monti, 2007;Oak et al, 2000). However, not all studies support this relationship (Lusher, Chandler, & Ball, 2001).…”

Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: Exploratory findings

“…Second is that since this study was conceived, several other important polymorphisms and associations have been further researched (e.g. Johnson et al, 2011; Johnson et al, 2013; McGeary et al, 2007; Ray et al, 2009; Skowronik et al, 2006; Varga et al, 2012). Moreover, we attempted to examine our results in light of the importance of the L A L A 5-HTTLPR genotype however our cell sizes were too small.…”

“…G-protein-linked D4 receptor activation attenuates signaling by inhibiting adenylyl cyclase coupling. This inhibition is blunted by the presence of the DRD4 7-repeat allele resulting in decreased receptor sensitivity and is associated with increased measures of novelty seeking and addiction phenotypes (Asghari et al 1995; Ebstein et al 1998;Ebstein, 2006; McGeary et al, 2007; Oak et al, 2000). …”