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  • Support for Cloninger s personality

    2019-07-19

    Support for Cloninger\'s personality theory comes also from molecular genetic studies. Given the high heritability of personality it is plausible that gene variants explain variance in RD. In DY131 to endocrine studies, which relate hormone levels mostly in the periphery (blood, saliva, urine) to personality, genetic studies investigating neurotransmitter relevant polymorphisms with putative effects on central nervous gene expression represent a more direct approach. In a small healthy Korean sample (N=115) the T-182C polymorphism of the norepinephrine transporter was associated with RD (Ham, Choi, Lee, Kang, & Lee, 2005). Yamano et al. (2008) found an association between RD and a single nucleotide polymorphism (SNP) on the phenylethanolamine N-methyltransferase (PNMT) gene (rs3764351) in a sample of N=85 Japanese healthy females. PNMT converts norepinephrine (NE) to epinephrine and therefore has an effect on noradrenaline availability. In a further study from Japan on N=324 healthy participants, a VNTR polymorphism on the MAO-A gene was associated with novelty seeking and RD (Shiraishi et al., 2006). MAO-A catabolizes the monoamines noradrenaline and serotonin (5-HT). Therefore, MAO-A influences besides PNMT noradrenaline DY131 levels. However, in a sample of N=370 Chinese female participants the positive association between the MAO-A VNTR and RD could not be replicated (Yu et al., 2005). Given that personality traits are polygenetically determined, there must be numerous gene variants involved in the expression of personality (see Montag & Reuter, 2014). If Cloninger\'s theory is valid than all genetic factors influencing the activity of the noradrenergic system should be potential candidate genes for disentangling the molecular genetic basis of RD. Besides the genes coding for PNMT, MAO-A and catechol-O-methyltransferase (COMT; catabolizing NE and dopamine (DA) in the synaptic cleft), the dopamine-β-hydroxylase (DBH) gene deserves testing for an association with RD. DBH metabolizes dopamine to noradrenaline and therefore has an influence on NE availability. Polymorphisms on the DBH gene have been successfully associated with various phenotypes. Most interestingly, Punchaichira, Prasad, Deshpande, and Thelma (2016) could show that the SNP rs1611115 (C-970T), located in the distal promoter region of the DBH gene, is functional, i.e. impacts the enzyme quantity of dopamine-β-hydroxylase. This finding corroborates a previous study showing that rs1611115 could explain up to 50% of the variance in DBH activity (Zabetian et al., 2001). A clear allele load effect could be demonstrated in both studies with highest enzymatic activity in carriers of the CC genotype, intermediate activity in heterozygous CT carriers and lowest activity in carriers homozygous for the T allele. Genetic expression analyses supported the endocrine studies. DBH gene expression rates were also dependent of rs1611115 (C-970T) and again the C allele is associated with significantly higher activity than the T allele (Barrie et al., 2014, Chen et al., 2010). In sum, lower enzyme activity in T-allele carriers might be associated with lower NE levels. There is plenty of evidence that rs1611115 effects phenotypes related to catecholaminergic activity. With respect to drug addiction carriers of the TT genotype show increased severity of heroin use (Xie et al., 2013) and poorer cocaine treatment outcomes (Kosten et al., 2013). Moreover, disulfiram, a pharmacological drug influencing DBH activity, is successfully applied in the treatment of substance and non-substance addictions (Carroll et al., 2004, Skinner et al., 2014). Recently, Yang, Balodis, Lacadie, Xu, and Potenza (2016) demonstrated that rs1611115 influences brain activity in the amygdala, the ventromedial prefrontal cortex, and striatal areas in response to emotional and motivational cues in both pathological gamblers as well as in healthy controls. More precisely, T allele carriers showed a reduced BOLD response to gambling, drug, or sad cues as compared to participants homozygous for the C allele (genotype CC). Noteworthy, rs1611115 has been also successfully associated with personality (Hess et al., 2009): Carriers of the TT genotype showed higher neuroticism and novelty seeking (NS) scores as compared to subjects carrying at least one C allele in a sample of N=637 patients with personality disorder. Although the authors had also included N=387 healthy controls in order to compare the genotype frequencies between patients and controls (no effect), the influence of rs1611115 on personality was not reported for the control sample.