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

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
Biological Psychiatry (Impact Factor: 10.26). 02/2007; 61(1):87-92. DOI: 10.1016/j.biopsych.2006.05.025
Source: PubMed


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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    • "4 long allele has been positively selected , which suggests that it likely confers some type of adaptive advan - tage ( Ding et al . , 2002 ; Oak et al . , 2000 ) . Although the long allele has been associated with attentional disorders in prior work ( Gizer & Waldman , 2012 ; Bidwell et al . , 2011 ; Gizer et al . , 2009 ; Munafò et al . , 2008 ; Laucht et al . , 2005 , 2007 ; Langley et al . , 2004 ; Hutchison et al . , 2003 ; Kustanovich et al . , 2003 ; Manor et al . , 2001 ; Swanson U n c o r r e c t e d"
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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 · 4.09 Impact Factor
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    • "We accordingly suggest that focusing on this particular gene is likely to be fruitful in the investigation of G × C interaction. Previous work has found associations between the 7R allele of DRD4 and certain behavioral traits, including novelty seeking (Laucht, Becker, Blomeyer, & Schmidt, 2007), heavy drinking (Laucht et al., 2007), and financial risk taking (Dreber et al., 2009), but these associations have not always been replicated (Munafò, Yalcin, Willis- Owen, & Flint, 2008). Further, evidence indicates that carriers of this variant are sometimes better socialized than noncarriers, having superior attentional control (Sheese et al., 2007) and greater prosocial orientations (Sasaki et al., 2013). "
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    ABSTRACT: Prior research suggests that cultural groups vary on an overarching dimension of independent versus interdependent social orientation, with European Americans being more independent, or less interdependent, than Asians. Drawing on recent evidence suggesting that the dopamine D4 receptor gene (DRD4) plays a role in modulating cultural learning, we predicted that carriers of DRD4 polymorphisms linked to increased dopamine signaling (7- or 2-repeat alleles) would show higher levels of culturally dominant social orientations, compared with noncarriers. European Americans and Asian-born Asians (total N = 398) reported their social orientation on multiple scales. They were also genotyped for DRD4. As in earlier work, European Americans were more independent, and Asian-born Asians more interdependent. This cultural difference was significantly more pronounced for carriers of the 7- or 2-repeat alleles than for noncarriers. Indeed, no cultural difference was apparent among the noncarriers. Implications for potential coevolution of genes and culture are discussed.
    Psychological Science 04/2014; 25(6). DOI:10.1177/0956797614528338 · 4.43 Impact Factor
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    • "The present study contributes to an accumulating body of research, suggesting that sex differences exist in the dopaminergic modulation of adolescent sexual onset and other forms of problem behavior. Sex differences in DRD4 effects, both direct and interactive, have been detected in a number of studies on a range of phenotypes involved in risky behaviors [17] [31]. The precise biological mechanisms involved constitute an important target for future research. "
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    ABSTRACT: Early sexual onset and its consequences disproportionately affect African-American youth, particularly male youth. The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (gene × environment [G × E] effects). The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African-Americans. Hypotheses were tested with self-report, biospecimen, and census data from five prospective studies of male and female African-American youth in rural Georgia communities, N = 1,677. Early sexual onset was defined as intercourse before age 14. No significant G × E findings emerged for female youth. Male youth with a DRD4 long allele were more likely than those with two DRD4 short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification rather than a vulnerability factor.
    Journal of Adolescent Health 04/2014; 55(2). DOI:10.1016/j.jadohealth.2014.02.019 · 3.61 Impact Factor
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