Novelty Seeking Involved in Mediating the Association Between the Dopamine D4 Receptor Gene Exon III Polymorphism and Heavy Drinking in Male Adolescents: Results from a High-Risk Community Sample
ABSTRACT Previous research suggests that personality traits, particularly novelty seeking (NS), increase the risk of substance abuse. One possible explanation to account for this association relates to common genetic factors. The aim of this study was to examine whether allelic variants of the dopamine D4 receptor gene (DRD4) are associated with alcohol use in adolescents and to determine the extent to which these links are mediated by NS.
Three hundred three adolescents (144 male participants, 159 female participants, approximately 15 years old) from a high-risk community sample completed self-report questionnaires measuring alcohol intake and temperament (Junior Temperament and Character Inventory [JTCI]). DNA was genotyped for the DRD4 exon III polymorphism.
Male participants carrying the 7-repeat allele of DRD4 drank higher maximum amounts of alcohol per occasion and had greater lifetime rates of heavy drinking than male participants without this allele. Higher levels of NS were associated with higher alcohol intake in both genders. Multiple regression analyses support the role of NS in mediating the relationship between DRD4 and heavy drinking in male adolescents but not in female adolescents.
These findings extend previous work highlighting the significance of personality traits as a mediating factor between genetic susceptibility and substance use during the period of early experimental use.
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ABSTRACT: Humans with seven or more repeats in exon III of the DRD4 gene (long DRD4 carriers) sometimes demonstrate impaired attention, as seen in attention-deficit hyperactivity disorder, and at other times demonstrate heightened attention, as seen in addictive behavior. Although the clinical effects of DRD4 are the focus of much work, this gene may not necessarily serve as a "risk" gene for attentional deficits, but as a plasticity gene where attention is heightened for priority items in the environment and impaired for minor items. Here we examine the role of DRD4 in two tasks that benefit from selective attention to high-priority information. We examine a category learning task where performance is supported by focusing on features and updating verbal rules. Here, selective attention to the most salient features is associated with good performance. In addition, we examine the Operation Span (OSPAN) task, a working memory capacity task that relies on selective attention to update and maintain items in memory while also performing a secondary task. Long DRD4 carriers show superior performance relative to short DRD4 homozygotes (six or less tandem repeats) in both the category learning and OSPAN tasks. These results suggest that DRD4 may serve as a "plasticity" gene where individuals with the long allele show heightened selective attention to high-priority items in the environment, which can be beneficial in the appropriate context.Journal of Cognitive Neuroscience 09/2014; 27(3):1-13. DOI:10.1162/jocn_a_00724 · 4.69 Impact Factor
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ABSTRACT: This study was designed to investigate a genetic moderation effect of dopamine receptor 4 gene (DRD4) alleles that have seven or more repeats (long alleles) on an intervention to deter drug use among rural African American adolescents in high-risk families. Adolescents (N = 291, M age = 17) were assigned randomly to the Adults in the Making (AIM) program or to a control condition and were followed for 27.5 months. Adolescents provided data on drug use and vulnerability cognitions three times after pretest. Pretest assessments of caregiver depressive symptoms, disruption in the home, and support toward the adolescent were used to construct a family risk index. Adolescents living in high-risk families who carried at least one DRD4 long allele and were assigned to the control condition evinced greater escalations in drug use than did (a) adolescents who lived in high-risk families, carried the DRD4 long allele, and were assigned to AIM, or (b) adolescents assigned to either condition who carried no DRD4 long alleles. AIM-induced reductions in vulnerability cognitions were responsible for the Family Risk × AIM × DRD4 status drug use prevention effects. These findings support differential susceptibility predictions and imply that prevention effects on genetically susceptible individuals may be underestimated.Development and Psychopathology 02/2015; 27(1):37-49. DOI:10.1017/S095457941400128X · 4.89 Impact Factor
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