A functional dopamine-β-hydroxylase gene promoter polymorphism is associated with impulsive personality styles, but not with affective disorders

Abstract

Dopamine-β-hydroxylase (DβH) catalyzes the conversion of dopamine to norepinephrine in central noradrenergic and adrenergic neurons and thus is critically involved in the biosynthesis of catecholamines. There are equivocal findings concerning the question whether or not DßH activity levels are altered in affective disorders or in subtypes of affective disorders. Moreover, information about the role of dopamine beta-hydroxylase (DBH) genotype, which explains a large part of the variance of enzymatic activity, in affective disorders and personality dimensions is limited. To resolve these inconsistencies, association tests were performed using four independent samples, healthy volunteers (N = 387), patients with affective disorders (N = 182), adult attention deficit hyperactivity disorder (ADHD) patients (N = 407), and patients with personality disorders (N = 637). In the latter two samples, the revised NEO personality inventory (NEO-PI-R) was administered. All participants were genotyped for a putatively functional single nucleotide polymorphism (C-1021T, rs1611115). No differences in DBH C-1021T genotype distribution were observed between patients with affective disorders and healthy control subjects. Also when the patient sample was divided into uni- and bipolar patients versus controls, no significant differences emerged. Furthermore, no clear-cut association was detected between the TT genotype and personality disorder clusters while there was a significant association with adult ADHD. However, personality disorder patients carrying the DBH TT genotype exhibited higher neuroticism and novelty seeking scores as compared to individuals with the CC or CT genotype. Analyses on the level of the neuroticism and novelty seeking subscales revealed that the DBH TT genotype was primarily associated with personality features related to impulsiveness and aggressive hostility. Also adult ADHD patients carrying the homozygous TT genotypes displayed by significantly increased neuroticism scores; when both personality disorder and adult ADHD patient were analyzed together, TT carriers also displayed by significantly lower conscientiousness levels. Our results thus do not implicate the DBH C-1021T polymorphism in the pathophysiology of depressive disorders or personality disorders, yet homozygosity at this locus appears to increase the risk towards personality traits related to impulsiveness, aggression and related disease states, namely adult ADHD. These data argue for a dimensional rather than categorical effect of genetic variance in DBH activity; accordingly, the inconsistency of previous findings concerning DβH levels in affective disorders might be caused by the underlying association of the TT genotype at DBH-1021 with impulsive personality traits. © 2008 Springer-Verlag.