Recent developments in molecular genetics offer the possibility of finding specific genes of major effect for personality traits as well as forms of psy-chopathology. Ebstein et al. (1996) first reported an association between alleles of the Dopamine Receptor D4 gene and the trait of novelty seeking as measured by a scale developed by Cloninger (1987). There are two common forms of the gene in Western populations: a short form with 4 repeats of the base sequence and a long form with 7 repeats. The longer form is associated with high scores on novelty seeking and the short form with low to moderate scores on this scale. Novelty Seeking (NS) correlates very highly (r about .7) with the ZKPQ scale Impulsive Sensation Seeking (Zuckerman & Cloninger, 1996). Soon there were some successful replications and some unsuccessful ones leading Baron (1998) to conclude that the association between the trait (sometimes measured by other tests) and gene was non-existent. However, a more recent review by Prolo and Licino (2002) reports 11 successful and 10 unsuccessful attempts to replicate.
When positive results are obtained the gene only accounts for about 10% at maximum of the genetic variance so that other genes must be involved. Comings, Saucier, & MacMurray (2002) found that 4 dopamine receptor genes contributed to 5.25% of the variance of novelty seeking in an additive manner with each gene contributing a small part of the total genetic variance. Noble et al. (1998) found similar additive effects of the DRD2 and DRD4 genes.
Apart from additive genetical effects, there may be interactive effects which could decrease the chances of finding the main effect of D4 in some studies. Strobel, Lesch, and Brocke (2003) found that while the DRD4 long allele was not associated with high NS scores alone; but when the short allele of the serotonin transporter gene and an allele of the catechol-O-methyltransferase (COMT) were present the association of NS with the DRD4 alleles was significant. A similar kind of interaction was found for genetic effects on infant exploratory behavior, involving the DRD4 receptor and a serotonin transporter gene (Ebstein & Auerbach, 2002; Ebstein et al., 1998).
The DRD4 is also associated with disorders characterized by impul-sivity and sensation seeking such as drug and alcohol abuse and attention-deficit/hyperactivity disorder (Ebstein & Kotler, 2002). The DRD2 dopamine gene has also been associated with alcoholism, ADHD, pathological gambling, and smoking in some, but not all, studies (Comings et al., 2002).
Several dopamine receptors seem to play a significant role in sensation seeking and impulsivity and the serotonin transporter gene may play an interactive role. Impulsive sensation seeking may be involved in approach behavior, mediated by the dopamine neurotransmitters, whereas serotonin may inhibit or delay approach behavior. This hypothesis will be further elaborated in subsequent parts of this chapter.
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