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.Molecular genetic studies on novelty seeking have confirmed theexpected importance of nonlinear gene gene and gene environmentinteractions in novelty seeking.A polymorphism of the dopaminetransporter is associated with individual differences in initiating andcontinuing to smoke cigarettes, an effect which is mediated by the jointassociation of cigarette smoking and the dopamine transporter with noveltyseeking [48].In addition, the dopamine receptor DRD4 exon 3 seven-repeatallele has been associated with high novelty seeking and increased risk ofopiate dependence [49].Other work has shown that novelty seeking isassociated with the ten-repeat allele of the dopamine transporter DAT1when the DRD4 seven-repeat allele is absent [50].Novelty seeking also depends on the three-way interaction of DRD4 withcathecol-O-methyl-transferase (COMT) and the serotonin transporter locuspromoter s regulatory region (5-HTTLPR).In the absence of the short 5-HTTLPR allele (5HTTLPR L/L genotype) and in the presence of the highactivity COMT Val/Val genotype, novelty seeking scores are higher in thepresence of the DRD4 seven-repeat allele than in its absence [51].Furthermore, within families, siblings who shared identical genotypegroups for all three polymorphisms (COMT, DRD4, and 5-HTTLPR) hadsignificantly correlated novelty seeking scores (intraclass correlation ¼ 0.39in 49 subjects, p50.008).In contrast, sibs with dissimilar genotypes in atleast one polymorphism showed no significant correlation for noveltyseeking (intraclass coefficient ¼ 0.18 in 110 subjects, p ¼ 0.09).Similarinteractions were also observed between these three polymorphisms andnovelty seeking in an independent sample of unrelated subjects [51] andhave been replicated by independent investigators [52].ANTISOCIAL PERSONALITY DISORDER: A REVIEW _________________________________ 133Gene environment interaction has also been demonstrated for TCI noveltyseeking in prospective population-based studies [53 55].The TCI wasadministered to two large birth cohorts of Finnish men and women, and theindividuals who scored in the top 10% and bottom 10% of TCI noveltyseeking were genotyped for the exon 3 repeat polymorphism of DRD4.Thefour-repeat and seven-repeat alleles were most common in the Finnishsample [53,54], as is usual throughout the world [56].The two-repeat andfive-repeat alleles, which are rare in the Americas and Africa, were more thanthree times as frequent (16% versus 5%) in Finns who were very high innovelty seeking than in those who were very low in novelty seeking [53,54],and this difference was replicated in an independent sample [54].Theassociation with the two-repeat and five-repeat alleles was strongest for thetwo most adaptive aspects of novelty seeking, exploratory excitability andimpulsive decision making [54].Finnish men and women with the two-repeatand five-repeat alleles were higher in novelty seeking as adults if they hadexperienced a hostile childhood environment, as measured by maternalreports of emotional distance and a strict authoritarian disciplinary style withphysical punishment [55].The effect of a hostile childhood environment onnovelty seeking was significant for the total novelty seeking score and for thespiritual aspect of novelty seeking (exploratory excitability) but not forthe intellectual aspect of novelty seeking (impulsive decision making).Themothers reports of childhood environment were obtained when the childrenwere aged 18 to 21 years, and genotyping and personality assessment ofnovelty seeking was done independently 15 years later.If children had thetwo-repeat or five-repeat alleles of the DRD4 polymorphism, their TCInovelty seeking scores were high if they were reared in a hostile childhoodenvironment and their novelty seeking scores were low if they were reared ina kind and cooperative environment [ Pobierz caÅ‚ość w formacie PDF ]