2009). In general, the association between DA activity and depression (Dunlop and Nemeroff 2007) is based on the fact that the neurotransmitter DA is involved in approach behavior (Schultz 1998) and depression is related to the deficits in the approach system associated with reduces positive affect (see Shankman and Klein 2003 for a review). To sum up, contrary to empirical next findings mentioned above prominent personality theories postulate orthogonality of personality dimensions, but growing empirical evidence indicates a negative correlation between traits of positive and NEM (for an overview see Reuter 2008). Heritability estimates

for personality traits as Inhibitors,research,lifescience,medical well as for psychopathologies are rather high indicating that the genetic background (genotype) of a person accounts substantially for individual differences in behavior and the predisposition to psychiatric disorders. Genetic association Inhibitors,research,lifescience,medical studies provide considerable evidence that DA genes are associated with personality traits and a range of psychiatric phenotypes. For instance, for the well-studied DA candidate genes coding for catechol-O-methyltransferase (COMT) and DRD2, a significant

interaction for the total Behavioral Activation System Inhibitors,research,lifescience,medical (BAS) scale related to PEM and also higher scores on extraversion and PEM for COMT valine (Val) allele carriers have been reported (Reuter and Hennig 2005; Reuter et al. 2006). In line with the “Yin and Yang principle of dopamine” results for the COMT polymorphism showed an association Inhibitors,research,lifescience,medical of the methionine (Met) allele with personality traits primarily related to NEM (Enoch et al. 2003; Eley et al. 2003; Rujescu et al. 2003). Despite this convergent evidence, the proportion of variance accounted

for by a single polymorphism is rather low. Complex phenotypes of high heritability such as personality traits are influenced by the interplay of many Inhibitors,research,lifescience,medical different genes (Reif and Lesch 2003), resulting in a wide variance of individual behavioral dispositions. In order to investigate the role of the DA system for personality, we have to keep in mind that DA genes interact to determine the efficacy of the DA system by influencing the expression and distribution of the gene products within Batimastat the brain. In particular, DA activity depends on synthesis rates, catabolism, and receptor density but also on further enzymes and proteins regulating DA neurotransmission (see Opmeer et al. for an overview). Numerous polymorphisms in the corresponding genes can have major influence on DA metabolism and neurotransmission. A vast body of evidence from studies in humans as well as animals illustrates the pivotal role of COMT and the dopamine transporter (DAT1) in DA neurotransmission.