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: 10.25). 02/2007; 61(1):87-92. DOI: 10.1016/j.biopsych.2006.05.025
Source: PubMed

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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    • "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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    • "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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    • "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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