Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of Novelty Seeking in a German population

Since the observation of an association between the dopamine D4 receptor (D RD4) exon III polymorphism and the temperament trait of Novelty Seeking,(1) replication studies have yielded both positive(2-5) and negative(6-12) res ults. This raised the question whether the initial findings must be regarde d as false positives.(13) However, demographic or methodological difference s between studies may have obscured the small effect of the DRD4 polymorphi sm on Novelty Seeking.(14) Examination of clinical or older cohorts may hav e led to an underestimation of possible associations due to a restricted va riation of Novelty Seeking in these cohorts. The use of different questionn aires provides another source of variation. In order to replicate the initi al findings as precisely as possible, a cohort of 136 healthy, young volunt eers was genotyped, and Novelty Seeking was ascertained using the TpQ.(15,1 6) addition, further aspects of novelty seeking behavior have been ascertai ned through additional trait measures. We could observe the reported associ ation between long DRD4 alleles and significantly elevated scores (age- and sex-residualized) on the TPQ-Novelty Seeking total scale as well as on two of the subscales, Exploratory Excitability and Extravagance. The results p rovide further confirmation for the role of the DRD4 exon III polymorphism in modulation of Novelty Seeking. In addition, the pattern of associations between the polymorphism and other scales suggests that this polymorphism h as its effect on exploratory, extravagant, and extraverted, rather than on impulsive and monotony-avoidant subtypes of Novelty Seeking.