1% of variance. To gain deeper insight into the contribution of DA genes on NEM, further work will focus on additional polymorphisms within these genes or others contributing to variability in DA function. A potential candidate is the DA catabolizing enzyme Monoamine Oxidase B (MAOB) that has also been associated

with NEM before (Dlugos et al. 2009). Despite the high number of participants in this study, three-way research interaction analyses of variance were not possible because they require an even larger sample size. However, personality traits appear to be shaped by many genetic variants each making a small contribution. The issue of the relationship of genetic effects on personality variables to clinical conditions Inhibitors,research,lifescience,medical is well established

Inhibitors,research,lifescience,medical for personality traits such as neuroticism (being shy, moody, anxious, and sad) representing a vulnerability factor for depression (Kendler and Myers 2010). Therefore, it is likely that this is also true for the Sadness dimension of the ANPS. Moreover, the question arises whether the continuum model for Sadness is applicable to a clinical relevant sample of depressed patients. In that case, carriers of the Inhibitors,research,lifescience,medical Val/Val and 9R/9R genotype configuration should show lower severity of depression in analogy to lower expression of Sadness in healthy subjects. We suggest that genotype configurations related to PEM are protective against NEM and therefore constitute a resilience factor against depression. Additionally, the postulated distribution of COMT and DAT1 variants resulting in balanced DA levels could be analyzed by fMRI studies in healthy and depressed Inhibitors,research,lifescience,medical subjects. The detection of functional and structural connectivity between the PFC and striatal areas dependent on the proposed genotype configurations would further support our findings. Differences between depressed patients and healthy controls reflecting alterations in DA function will shed light on the contribution Inhibitors,research,lifescience,medical and impact of COMT and DAT1 interaction in regional brain

activation and implications for depression. In conclusion, we found a significant interaction of COMT × DAT1 on human personality. Thereby, the genotype constellation COMT Val/Val and DAT1 9R/9R showed lowest Sadness levels and therefore might consequently contribute 4-Aminobutyrate aminotransferase to individual differences in risk and resilience for depression. Nevertheless, further research using molecular genetics and genetic imaging techniques will give insights into the precise neural mechanisms underlying the interaction of COMT and DAT1. Acknowledgments This study was in part supported by the German Research Association to MR (Grant No. DFG-RE 1692/4-1). Supporting Information Additional Supporting Information may be found in the online version of this article: Table S1. Correlation matrix for the dimensions Fear, Anger, Sadness, Seek, Care, and Play of the Affective Neuroscience Personality Scales. Click here to view.